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Mei X, Yang Z, Wang X, Shi A, Blanchard J, Elahi F, Kang H, Orive G, Zhang YS. Integrating microfluidic and bioprinting technologies: advanced strategies for tissue vascularization. LAB ON A CHIP 2025; 25:764-786. [PMID: 39775452 DOI: 10.1039/d4lc00280f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Tissue engineering offers immense potential for addressing the unmet needs in repairing tissue damage and organ failure. Vascularization, the development of intricate blood vessel networks, is crucial for the survival and functions of engineered tissues. Nevertheless, the persistent challenge of ensuring an ample nutrient supply within implanted tissues remains, primarily due to the inadequate formation of blood vessels. This issue underscores the vital role of the human vascular system in sustaining cellular functions, facilitating nutrient exchange, and removing metabolic waste products. In response to this challenge, new approaches have been explored. Microfluidic devices, emulating natural blood vessels, serve as valuable tools for investigating angiogenesis and allowing the formation of microvascular networks. In parallel, bioprinting technologies enable precise placement of cells and biomaterials, culminating in vascular structures that closely resemble the native vessels. To this end, the synergy of microfluidics and bioprinting has further opened up exciting possibilities in vascularization, encompassing innovations such as microfluidic bioprinting. These advancements hold great promise in regenerative medicine, facilitating the creation of functional tissues for applications ranging from transplantation to disease modeling and drug testing. This review explores the potentially transformative impact of microfluidic and bioprinting technologies on vascularization strategies within the scope of tissue engineering.
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Affiliation(s)
- Xuan Mei
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
| | - Ziyi Yang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
- School of Biological Science, University of California Irvine, Irvine, CA 92697, USA
| | - Xiran Wang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
- Department of Mechanical and Aerospace Engineering, University of California, San Diego, San Diego, CA 92161, USA
| | - Alan Shi
- Brookline High School, Brookline, MA 02445, USA
| | - Joel Blanchard
- Departments of Neurology, Neuroscience, and Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Fanny Elahi
- Departments of Neurology, Neuroscience, and Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY 10468, USA
| | - Heemin Kang
- Department of Materials Science and Engineering, Korea University, Seoul 02841, Republic of Korea.
- College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - Gorka Orive
- NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
- Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain
- Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain
- University Institute for Regenerative Medicine and Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria-Gasteiz, 01007, Spain
- Singapore Eye Research Institute, Singapore 169856, Singapore
| | - Yu Shrike Zhang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
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Landau S, Okhovatian S, Zhao Y, Liu C, Shakeri A, Wang Y, Ramsay K, Kieda J, Jiang R, Radisic M. Bioengineering vascularization. Development 2024; 151:dev204455. [PMID: 39611864 PMCID: PMC11698057 DOI: 10.1242/dev.204455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
This Review explores the rapidly evolving field of bioengineered vasculature, a key area of focus in tissue engineering and regenerative medicine. The broad relevance of this topic is attributed to its impacts on a wide range of biological processes, enabling studies in tissue development, fundamental biology and drug discovery, and the applications in tissue engineering and regenerative medicine. We outline the design criteria for bioengineered vasculature and the methodologies for constructing these systems by self-assembly and in microfluidics, organs-on-a-chip and macroscale tubular systems that often rely on biofabrication approaches such as 3D printing. We discuss existing challenges in developing functional vasculature that closely mirrors its native equivalent, including achieving hierarchical branching with organ and vessel-specific endothelial and supporting cells, providing perusable vasculature within organoids and scaling the systems for implantation and direct vascular anastomosis.
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Affiliation(s)
- Shira Landau
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Sargol Okhovatian
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Yimu Zhao
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
- Acceleration Consortium, University of Toronto, Toronto M5G 1X6, ON, Canada
| | - Chuan Liu
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Amid Shakeri
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Ying Wang
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Kaitlyn Ramsay
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Jennifer Kieda
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Richard Jiang
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
| | - Milica Radisic
- Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3G9, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, ON, Canada
- Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto M5S 3E5, ON, Canada
- Terence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto M5S 3E1, ON, Canada
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Liu Y, Huang T, Yap NA, Lim K, Ju LA. Harnessing the power of bioprinting for the development of next-generation models of thrombosis. Bioact Mater 2024; 42:328-344. [PMID: 39295733 PMCID: PMC11408160 DOI: 10.1016/j.bioactmat.2024.08.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 08/07/2024] [Accepted: 08/29/2024] [Indexed: 09/21/2024] Open
Abstract
Thrombosis, a leading cause of cardiovascular morbidity and mortality, involves the formation of blood clots within blood vessels. Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions, limiting the research in understanding the mechanisms of thrombosis. Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels. This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies, including the incorporation of key structural, biochemical and mechanical features, the selection of appropriate biomaterials and cell sources, and the challenges and future directions in the field. The advancements in bioprinting techniques, such as multi-material bioprinting and microfluidic integration, have enabled the development of physiologically relevant models of thrombosis. The future of bioprinted models of thrombosis lies in the integration of patient-specific data, real-time monitoring technologies, and advanced microfluidic platforms, paving the way for personalized medicine and targeted interventions. As the field of bioprinting continues to evolve, these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes. The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.
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Affiliation(s)
- Yanyan Liu
- School of Biomedical Engineering, The University of Sydney, Darlington, NSW, 2008, Australia
| | - Tao Huang
- School of Biomedical Engineering, The University of Sydney, Darlington, NSW, 2008, Australia
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006, Australia
| | - Nicole Alexis Yap
- School of Biomedical Engineering, The University of Sydney, Darlington, NSW, 2008, Australia
| | - Khoon Lim
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006, Australia
- School of Medical Sciences, The University of Sydney, Darlington, NSW 2008, Australia
- The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Camperdown, NSW, 2006, Australia
| | - Lining Arnold Ju
- School of Biomedical Engineering, The University of Sydney, Darlington, NSW, 2008, Australia
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006, Australia
- The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Camperdown, NSW, 2006, Australia
- Heart Research Institute, Camperdown, Newtown, NSW 2042, Australia
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Maurat E, Raasch K, Leipold AM, Henrot P, Zysman M, Prevel R, Trian T, Krammer T, Bergeron V, Thumerel M, Nassoy P, Berger P, Saliba AE, Andrique L, Recher G, Dupin I. A novel in vitro tubular model to recapitulate features of distal airways: the bronchioid. Eur Respir J 2024; 64:2400562. [PMID: 39231631 PMCID: PMC11627163 DOI: 10.1183/13993003.00562-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/21/2024] [Indexed: 09/06/2024]
Abstract
BACKGROUND Airflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerous in vitro models of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems. METHODS We developed a so-called bronchioid model by encapsulating human bronchial adult stem cells derived from clinical samples in a tubular scaffold made of alginate gel. RESULTS This template drives the spontaneous self-organisation of epithelial cells into a tubular structure. Fine control of the level of contraction is required to establish a model of the bronchiole, which has a physiologically relevant shape and size. Three-dimensional imaging, gene expression and single-cell RNA-sequencing analysis of bronchioids made of bronchial epithelial cells revealed tubular organisation, epithelial junction formation and differentiation into ciliated and goblet cells. Ciliary beating was observed, at a decreased frequency in bronchioids made of cells from COPD patients. The bronchioid could be infected by rhinovirus. An air-liquid interface was introduced that modulated gene expression. CONCLUSION Here, we provide a proof of concept of a perfusable bronchioid with proper mucociliary and contractile functions. The key advantages of our approach, such as the air‒liquid interface, lumen accessibility, recapitulation of pathological features and possible assessment of clinically relevant end-points, will make our pulmonary organoid-like model a powerful tool for preclinical studies.
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Affiliation(s)
- Elise Maurat
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- Equal contribution as joint first authors
| | - Katharina Raasch
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- Equal contribution as joint first authors
| | - Alexander M Leipold
- Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany
- University of Würzburg, Faculty of Medicine, Institute of Molecular Infection Biology (IMIB), Würzburg, Germany
| | - Pauline Henrot
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, Bordeaux, France
| | - Maeva Zysman
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, Bordeaux, France
| | - Renaud Prevel
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, Bordeaux, France
| | - Thomas Trian
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
| | - Tobias Krammer
- Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany
| | - Vanessa Bergeron
- VoxCell Facility, TBMcore UAR CNRS 3427, INSERM US 005, Univ-Bordeaux, Bordeaux, France
| | - Matthieu Thumerel
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, Bordeaux, France
| | - Pierre Nassoy
- Laboratoire Photonique, Numérique et Nanosciences, UMR 5298 CNRS, Univ-Bordeaux, Bordeaux, France
| | - Patrick Berger
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, Bordeaux, France
| | - Antoine-Emmanuel Saliba
- Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany
- University of Würzburg, Faculty of Medicine, Institute of Molecular Infection Biology (IMIB), Würzburg, Germany
| | - Laetitia Andrique
- VoxCell Facility, TBMcore UAR CNRS 3427, INSERM US 005, Univ-Bordeaux, Bordeaux, France
| | - Gaëlle Recher
- Laboratoire Photonique, Numérique et Nanosciences, UMR 5298 CNRS, Univ-Bordeaux, Bordeaux, France
| | - Isabelle Dupin
- Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France
- Institut Universitaire de France (IUF), Paris, France
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Chen A, Wang W, Mao Z, He Y, Chen S, Liu G, Su J, Feng P, Shi Y, Yan C, Lu J. Multimaterial 3D and 4D Bioprinting of Heterogenous Constructs for Tissue Engineering. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2307686. [PMID: 37737521 DOI: 10.1002/adma.202307686] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/06/2023] [Indexed: 09/23/2023]
Abstract
Additive manufacturing (AM), which is based on the principle of layer-by-layer shaping and stacking of discrete materials, has shown significant benefits in the fabrication of complicated implants for tissue engineering (TE). However, many native tissues exhibit anisotropic heterogenous constructs with diverse components and functions. Consequently, the replication of complicated biomimetic constructs using conventional AM processes based on a single material is challenging. Multimaterial 3D and 4D bioprinting (with time as the fourth dimension) has emerged as a promising solution for constructing multifunctional implants with heterogenous constructs that can mimic the host microenvironment better than single-material alternatives. Notably, 4D-printed multimaterial implants with biomimetic heterogenous architectures can provide a time-dependent programmable dynamic microenvironment that can promote cell activity and tissue regeneration in response to external stimuli. This paper first presents the typical design strategies of biomimetic heterogenous constructs in TE applications. Subsequently, the latest processes in the multimaterial 3D and 4D bioprinting of heterogenous tissue constructs are discussed, along with their advantages and challenges. In particular, the potential of multimaterial 4D bioprinting of smart multifunctional tissue constructs is highlighted. Furthermore, this review provides insights into how multimaterial 3D and 4D bioprinting can facilitate the realization of next-generation TE applications.
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Affiliation(s)
- Annan Chen
- Centre for Advanced Structural Materials, Department of Mechanical Engineering, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
- Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen, 518057, China
- CityU-Shenzhen Futian Research Institute, Shenzhen, 518045, China
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
- Engineering Research Center of Ceramic Materials for Additive Manufacturing, Ministry of Education, Wuhan, 430074, China
| | - Wanying Wang
- Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen, 518057, China
- CityU-Shenzhen Futian Research Institute, Shenzhen, 518045, China
- Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
| | - Zhengyi Mao
- Centre for Advanced Structural Materials, Department of Mechanical Engineering, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
- Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen, 518057, China
- CityU-Shenzhen Futian Research Institute, Shenzhen, 518045, China
| | - Yunhu He
- Centre for Advanced Structural Materials, Department of Mechanical Engineering, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
- Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen, 518057, China
- CityU-Shenzhen Futian Research Institute, Shenzhen, 518045, China
| | - Shiting Chen
- Centre for Advanced Structural Materials, Department of Mechanical Engineering, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
- Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen, 518057, China
- CityU-Shenzhen Futian Research Institute, Shenzhen, 518045, China
| | - Guo Liu
- Centre for Advanced Structural Materials, Department of Mechanical Engineering, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
- Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen, 518057, China
- CityU-Shenzhen Futian Research Institute, Shenzhen, 518045, China
| | - Jin Su
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
- Engineering Research Center of Ceramic Materials for Additive Manufacturing, Ministry of Education, Wuhan, 430074, China
| | - Pei Feng
- State Key Laboratory of High-Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha, 410083, China
| | - Yusheng Shi
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
- Engineering Research Center of Ceramic Materials for Additive Manufacturing, Ministry of Education, Wuhan, 430074, China
| | - Chunze Yan
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
- Engineering Research Center of Ceramic Materials for Additive Manufacturing, Ministry of Education, Wuhan, 430074, China
| | - Jian Lu
- Centre for Advanced Structural Materials, Department of Mechanical Engineering, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
- Centre for Advanced Structural Materials, City University of Hong Kong Shenzhen Research Institute, Greater Bay Joint Division, Shenyang National Laboratory for Materials Science, Shenzhen, 518057, China
- CityU-Shenzhen Futian Research Institute, Shenzhen, 518045, China
- Department of Materials Science and Engineering, City University of Hong Kong, Kowloon, Hong Kong, 999077, China
- Hong Kong Branch of National Precious Metals Material Engineering Research, Center (NPMM), City University of Hong Kong, Kowloon, Hong Kong, 999077, China
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Yu T, Yang Q, Peng B, Gu Z, Zhu D. Vascularized organoid-on-a-chip: design, imaging, and analysis. Angiogenesis 2024; 27:147-172. [PMID: 38409567 DOI: 10.1007/s10456-024-09905-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 01/11/2024] [Indexed: 02/28/2024]
Abstract
Vascularized organoid-on-a-chip (VOoC) models achieve substance exchange in deep layers of organoids and provide a more physiologically relevant system in vitro. Common designs for VOoC primarily involve two categories: self-assembly of endothelial cells (ECs) to form microvessels and pre-patterned vessel lumens, both of which include the hydrogel region for EC growth and allow for controlled fluid perfusion on the chip. Characterizing the vasculature of VOoC often relies on high-resolution microscopic imaging. However, the high scattering of turbid tissues can limit optical imaging depth. To overcome this limitation, tissue optical clearing (TOC) techniques have emerged, allowing for 3D visualization of VOoC in conjunction with optical imaging techniques. The acquisition of large-scale imaging data, coupled with high-resolution imaging in whole-mount preparations, necessitates the development of highly efficient analysis methods. In this review, we provide an overview of the chip designs and culturing strategies employed for VOoC, as well as the applicable optical imaging and TOC methods. Furthermore, we summarize the vascular analysis techniques employed in VOoC, including deep learning. Finally, we discuss the existing challenges in VOoC and vascular analysis methods and provide an outlook for future development.
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Affiliation(s)
- Tingting Yu
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China
- Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China
| | - Qihang Yang
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China
- Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China
| | - Bo Peng
- Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an, Shanxi, 710072, China
| | - Zhongze Gu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China
- Institute of Biomaterials and Medical Devices, Southeast University, Suzhou, Jiangsu, 215163, China
| | - Dan Zhu
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
- Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
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Hewes SA, Ahmad FN, Connell JP, Grande-Allen KJ. Technique for Rapidly Forming Networks of Microvessel-Like Structures. Tissue Eng Part C Methods 2024; 30:229-237. [PMID: 38568845 PMCID: PMC11971615 DOI: 10.1089/ten.tec.2023.0318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 03/12/2024] [Indexed: 04/05/2024] Open
Abstract
Modeling organ-blood barriers through the inclusion of microvessel networks within in vitro tissue models could lead to more physiologically accurate results, especially since organ-blood barriers are crucial to the normal function, drug transport, and disease states of vascularized organs. Microvessel networks are difficult to form, since they push the practical limits of most fabrication methods, and it is difficult to coax vascular cells to self-assemble into structures larger than capillaries. Here, we present a method for rapidly forming networks of microvessel-like structures using sacrificial alginate structures. Specifically, we encapsulated endothelial cells within short alginate threads, and then embedded them in collagen gel. Following enzymatic degradation of the alginate, the collagen gel contained a network of hollow channels seeded with cells, all surrounding a perfusable central channel. This method uses a 3D-printed coaxial extruder and syringe pumps to generate short threads in a way that is repeatable and easily transferrable to other labs. The cell-laden, sacrificial alginate threads can be frozen after fabrication and thawed before embedding without significant loss of cell viability. The ability to freeze the threads enables future scale-up and ease of use. Within millifluidic devices that restrict access to media, the threads enhance cell survival under static conditions. These results indicate the potential for use of this method in a range of tissue engineering applications.
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Affiliation(s)
- Sarah A. Hewes
- Department of Bioengineering, Rice University, Houston, Texas, USA
| | - Fariha N. Ahmad
- Department of Bioengineering, Rice University, Houston, Texas, USA
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Wei X, Xu H, Zhou M, Zhou Q, Li M, Liu Y. Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration. J Nanobiotechnology 2024; 22:150. [PMID: 38575923 PMCID: PMC11318316 DOI: 10.1186/s12951-024-02393-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 03/10/2024] [Indexed: 04/06/2024] Open
Abstract
Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.
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Affiliation(s)
- Xiaoling Wei
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Huaxing Xu
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Mengqi Zhou
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Qiangqiang Zhou
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Mingqiang Li
- School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
| | - Yuehua Liu
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China.
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China.
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9
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Angolkar M, Paramshetti S, Gahtani RM, Al Shahrani M, Hani U, Talath S, Osmani RAM, Spandana A, Gangadharappa HV, Gundawar R. Pioneering a paradigm shift in tissue engineering and regeneration with polysaccharides and proteins-based scaffolds: A comprehensive review. Int J Biol Macromol 2024; 265:130643. [PMID: 38467225 DOI: 10.1016/j.ijbiomac.2024.130643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 02/16/2024] [Accepted: 03/03/2024] [Indexed: 03/13/2024]
Abstract
In the realm of modern medicine, tissue engineering and regeneration stands as a beacon of hope, offering the promise of restoring form and function to damaged or diseased organs and tissues. Central to this revolutionary field are biological macromolecules-nature's own blueprints for regeneration. The growing interest in bio-derived macromolecules and their composites is driven by their environmentally friendly qualities, renewable nature, minimal carbon footprint, and widespread availability in our ecosystem. Capitalizing on these unique attributes, specific composites can be tailored and enhanced for potential utilization in the realm of tissue engineering (TE). This review predominantly concentrates on the present research trends involving TE scaffolds constructed from polysaccharides, proteins and glycosaminoglycans. It provides an overview of the prerequisites, production methods, and TE applications associated with a range of biological macromolecules. Furthermore, it tackles the challenges and opportunities arising from the adoption of these biomaterials in the field of TE. This review also presents a novel perspective on the development of functional biomaterials with broad applicability across various biomedical applications.
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Affiliation(s)
- Mohit Angolkar
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India
| | - Sharanya Paramshetti
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India
| | - Reem M Gahtani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia.
| | - Mesfer Al Shahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia.
| | - Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia.
| | - Sirajunisa Talath
- Department of Pharmaceutical Chemistry, RAK College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.
| | - Riyaz Ali M Osmani
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India.
| | - Asha Spandana
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India.
| | | | - Ravi Gundawar
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India.
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10
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Hewes SA, Ahmad FN, Connell JP, Grande-Allen KJ. Technique for rapidly forming networks of microvessel-like structures. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.06.22.546165. [PMID: 37961290 PMCID: PMC10634690 DOI: 10.1101/2023.06.22.546165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Modelling organ-blood barriers through the inclusion of microvessel networks within in vitro tissue models could lead to more physiologically accurate results, especially since organ-blood barriers are crucial to the normal function, drug transport, and disease states of vascularized organs. Microvessel networks are difficult to form, since they push the practical limit of most fabrication methods, and it is difficult to coax vascular cells to self-assemble into structures larger than capillaries. Here we present a method for rapidly forming networks of microvessel-like structures using sacrificial, alginate structures. Specifically, we encapsulated endothelial cells within short alginate threads, then embedded them in collagen gel. Following enzymatic degradation of the alginate, the collagen gel contained a network of hollow channels seeded with cells, all surrounding a perfusable central channel. This method uses a 3D printed coaxial extruder and syringe pumps to generate short threads in a way that is repeatable and easily transferrable to other labs. The cell-laden, sacrificial alginate threads can be frozen after fabrication and thawed before embedding without significant loss of cell viability. The ability to freeze the threads enables future scale up and ease of use. Within millifluidic devices that restrict access to media, the threads enhance cell survival under static conditions. These results indicate the potential for use of this method in a range of tissue engineering applications.
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Affiliation(s)
- Sarah A. Hewes
- Department of Bioengineering, Rice University, Houston, TX
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11
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Sun T, Xiang Y, Turner F, Bao X. Integrated Experimental and Mathematical Exploration of Modular Tissue Cultures for Developmental Engineering. Int J Mol Sci 2024; 25:2987. [PMID: 38474234 DOI: 10.3390/ijms25052987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/06/2024] [Accepted: 02/28/2024] [Indexed: 03/14/2024] Open
Abstract
Developmental engineering (DE) involves culturing various cells on modular scaffolds (MSs), yielding modular tissues (MTs) assembled into three-dimensional (3D) tissues, mimicking developmental biology. This study employs an integrated approach, merging experimental and mathematical methods to investigate the biological processes in MT cultivation and assembly. Human dermal fibroblasts (HDFs) were cultured on tissue culture plastics, poly(lactic acid) (PLA) discs with regular open structures, or spherical poly(methyl methacrylate) (PMMA) MSs, respectively. Notably, HDFs exhibited flattened spindle shapes when adhered to solid surfaces, and complex 3D structures when migrating into the structured voids of PLA discs or interstitial spaces between aggregated PMMA MSs, showcasing coordinated colonization of porous scaffolds. Empirical investigations led to power law models simulating density-dependent cell growth on solid surfaces or voids. Concurrently, a modified diffusion model was applied to simulate oxygen diffusion within tissues cultured on solid surfaces or porous structures. These mathematical models were subsequently combined to explore the influences of initial cell seeding density, culture duration, and oxygen diffusion on MT cultivation and assembly. The findings underscored the intricate interplay of factors influencing MT design for tissue assembly. The integrated approach provides insights into mechanistic aspects, informing bioprocess design for manufacturing MTs and 3D tissues in DE.
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Affiliation(s)
- Tao Sun
- Department of Chemical Engineering, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK
| | - Yu Xiang
- Department of Materials, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK
| | - Freya Turner
- Department of Chemical Engineering, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK
| | - Xujin Bao
- Department of Materials, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK
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12
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Wang P, Liao Q, Zhang H. Polysaccharide-Based Double-Network Hydrogels: Polysaccharide Effect, Strengthening Mechanisms, and Applications. Biomacromolecules 2023; 24:5479-5510. [PMID: 37718493 DOI: 10.1021/acs.biomac.3c00765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2023]
Abstract
Polysaccharides are carbohydrate polymers that are major components of plants, animals, and microorganisms, with unique properties. Biological hydrogels are polymeric networks that imbibe and retain large amounts of water and are the major components of living organisms. The mechanical properties of hydrogels are critical for their functionality and applications. Since synthetic polymeric double-network (DN) hydrogels possess unique network structures with high and tunable mechanical properties, many natural functional polysaccharides have attracted increased attention due to their rich and convenient sources, unique chemical structure and chain conformation, inherently desirable cytocompatibility, biodegradability and environmental friendliness, diverse bioactivities, and rheological properties, which rationally make them prominent constituents in designing various strong and tough polysaccharide-based DN hydrogels over the past ten years. This review focuses on the latest developments of polysaccharide-based DN hydrogels to comprehend the relationship among the polysaccharide properties, inner strengthening mechanisms, and applications. The aim of this review is to provide an insightful mechanical interpretation of the design strategy of novel polysaccharide-based DN hydrogels and their applications by introducing the correlation between performance and composition. The mechanical behavior of DN hydrogels and the roles of varieties of marine, microbial, plant, and animal polysaccharides are emphatically explained.
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Affiliation(s)
- Pengguang Wang
- Advanced Rheology Institute, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Qingyu Liao
- Advanced Rheology Institute, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hongbin Zhang
- Advanced Rheology Institute, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, China
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13
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Jiang H, Li X, Chen T, Liu Y, Wang Q, Wang Z, Jia J. Bioprinted vascular tissue: Assessing functions from cellular, tissue to organ levels. Mater Today Bio 2023; 23:100846. [PMID: 37953757 PMCID: PMC10632537 DOI: 10.1016/j.mtbio.2023.100846] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/21/2023] [Accepted: 10/26/2023] [Indexed: 11/14/2023] Open
Abstract
3D bioprinting technology is widely used to fabricate various tissue structures. However, the absence of vessels hampers the ability of bioprinted tissues to receive oxygen and nutrients as well as to remove wastes, leading to a significant reduction in their survival rate. Despite the advancements in bioinks and bioprinting technologies, bioprinted vascular structures continue to be unsuitable for transplantation compared to natural blood vessels. In addition, a complete assessment index system for evaluating the structure and function of bioprinted vessels in vitro has not yet been established. Therefore, in this review, we firstly highlight the significance of selecting suitable bioinks and bioprinting techniques as they two synergize with each other. Subsequently, focusing on both vascular-associated cells and vascular tissues, we provide a relatively thorough assessment of the functions of bioprinted vascular tissue based on the physiological functions that natural blood vessels possess. We end with a review of the applications of vascular models, such as vessel-on-a-chip, in simulating pathological processes and conducting drug screening at the organ level. We believe that the development of fully functional blood vessels will soon make great contributions to tissue engineering and regenerative medicine.
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Affiliation(s)
- Haihong Jiang
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Xueyi Li
- Sino-Swiss Institute of Advanced Technology, School of Micro-electronics, Shanghai University, Shanghai, China
| | - Tianhong Chen
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Yang Liu
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Qian Wang
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Zhimin Wang
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Institute for Biomedical and Pharmaceutical Technologies (SIBPT), Shanghai, China
| | - Jia Jia
- School of Life Sciences, Shanghai University, Shanghai, China
- Sino-Swiss Institute of Advanced Technology, School of Micro-electronics, Shanghai University, Shanghai, China
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14
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Le HT, Phan HL, Lenshof A, Duong VT, Choi C, Cha C, Laurell T, Koo KI. Ultrasound standing wave spatial patterning of human umbilical vein endothelial cells for 3D micro-vascular networks formation. Biofabrication 2023; 16:015009. [PMID: 37844581 DOI: 10.1088/1758-5090/ad03be] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 10/16/2023] [Indexed: 10/18/2023]
Abstract
Generating functional and perfusable micro-vascular networks is an important goal for the fabrication of large and three-dimensional tissues. Up to now, the fabrication of micro-vascular networks is a complicated multitask involving several different factors such as time consuming, cells survival, micro-diameter vasculature and strict alignment. Here, we propose a technique combining multi-material extrusion and ultrasound standing wave forces to create a network structure of human umbilical vein endothelial cells within a mixture of calcium alginate and decellularized extracellular matrix. The functionality of the matured microvasculature networks was demonstrated through the enhancement of cell-cell adhesion, angiogenesis process, and perfusion tests with microparticles, FITC-dextran, and whole mouse blood. Moreover, animal experiments exhibited the implantability including that the pre-existing blood vessels of the host sprout towards the preformed vessels of the scaffold over time and the microvessels inside the implanted scaffold matured from empty tubular structures to functional blood-carrying microvessels in two weeks.
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Affiliation(s)
- Huong Thi Le
- Department of Electrical, Electronic and Computer Engineering, University of Ulsan, Ulsan 44610, Republic of Korea
| | - Huu Lam Phan
- Department of Electrical, Electronic and Computer Engineering, University of Ulsan, Ulsan 44610, Republic of Korea
| | - Andreas Lenshof
- Department of Biomedical Engineering, Lund University, S-221 00 Lund, Sweden
| | - Van Thuy Duong
- Department of Electrical, Electronic and Computer Engineering, University of Ulsan, Ulsan 44610, Republic of Korea
| | - Cholong Choi
- Department of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
| | - Chaenyung Cha
- Department of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
| | - Thomas Laurell
- Department of Biomedical Engineering, Lund University, S-221 00 Lund, Sweden
| | - Kyo-In Koo
- Department of Electrical, Electronic and Computer Engineering, University of Ulsan, Ulsan 44610, Republic of Korea
- Basic-Clinical Convergence Research Institute, University of Ulsan, Ulsan, Republic of Korea
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15
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Zhao Q, Du X, Wang M. Electrospinning and Cell Fibers in Biomedical Applications. Adv Biol (Weinh) 2023; 7:e2300092. [PMID: 37166021 DOI: 10.1002/adbi.202300092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/29/2023] [Indexed: 05/12/2023]
Abstract
Human body tissues such as muscle, blood vessels, tendon/ligaments, and nerves have fiber-like fascicle morphologies, where ordered organization of cells and extracellular matrix (ECM) within the bundles in specific 3D manners orchestrates cells and ECM to provide tissue functions. Through engineering cell fibers (which are fibers containing living cells) as living building blocks with the help of emerging "bottom-up" biomanufacturing technologies, it is now possible to reconstitute/recreate the fiber-like fascicle morphologies and their spatiotemporally specific cell-cell/cell-ECM interactions in vitro, thereby enabling the modeling, therapy, or repair of these fibrous tissues. In this article, a concise review is provided of the "bottom-up" biomanufacturing technologies and materials usable for fabricating cell fibers, with an emphasis on electrospinning that can effectively and efficiently produce thin cell fibers and with properly designed processes, 3D cell-laden structures that mimic those of native fibrous tissues. The importance and applications of cell fibers as models, therapeutic platforms, or analogs/replacements for tissues for areas such as drug testing, cell therapy, and tissue engineering are highlighted. Challenges, in terms of biomimicry of high-order hierarchical structures and complex dynamic cellular microenvironments of native tissues, as well as opportunities for cell fibers in a myriad of biomedical applications, are discussed.
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Affiliation(s)
- Qilong Zhao
- Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Xuemin Du
- Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Min Wang
- Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong
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16
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Wang X, Shen Y, Shang M, Liu X, Munn LL. Endothelial mechanobiology in atherosclerosis. Cardiovasc Res 2023; 119:1656-1675. [PMID: 37163659 PMCID: PMC10325702 DOI: 10.1093/cvr/cvad076] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 02/11/2023] [Accepted: 02/21/2023] [Indexed: 05/12/2023] Open
Abstract
Cardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays a central role in maintaining vascular integrity and homeostasis and is in direct contact with the blood flow. Research over the past century has shown that mechanical perturbations of the vascular wall contribute to the formation and progression of atherosclerosis. While the straight part of the artery is exposed to sustained laminar flow and physiological high shear stress, flow near branch points or in curved vessels can exhibit 'disturbed' flow. Clinical studies as well as carefully controlled in vitro analyses have confirmed that these regions of disturbed flow, which can include low shear stress, recirculation, oscillation, or lateral flow, are preferential sites of atherosclerotic lesion formation. Because of their critical role in blood flow homeostasis, vascular endothelial cells (ECs) have mechanosensory mechanisms that allow them to react rapidly to changes in mechanical forces, and to execute context-specific adaptive responses to modulate EC functions. This review summarizes the current understanding of endothelial mechanobiology, which can guide the identification of new therapeutic targets to slow or reverse the progression of atherosclerosis.
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Affiliation(s)
- Xiaoli Wang
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310020, China
| | - Yang Shen
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China
| | - Min Shang
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310020, China
| | - Xiaoheng Liu
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China
| | - Lance L Munn
- Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
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17
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Chen J, Zhang D, Wu LP, Zhao M. Current Strategies for Engineered Vascular Grafts and Vascularized Tissue Engineering. Polymers (Basel) 2023; 15:polym15092015. [PMID: 37177162 PMCID: PMC10181238 DOI: 10.3390/polym15092015] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 04/21/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Blood vessels not only transport oxygen and nutrients to each organ, but also play an important role in the regulation of tissue regeneration. Impaired or occluded vessels can result in ischemia, tissue necrosis, or even life-threatening events. Bioengineered vascular grafts have become a promising alternative treatment for damaged or occlusive vessels. Large-scale tubular grafts, which can match arteries, arterioles, and venules, as well as meso- and microscale vasculature to alleviate ischemia or prevascularized engineered tissues, have been developed. In this review, materials and techniques for engineering tubular scaffolds and vasculature at all levels are discussed. Examples of vascularized tissue engineering in bone, peripheral nerves, and the heart are also provided. Finally, the current challenges are discussed and the perspectives on future developments in biofunctional engineered vessels are delineated.
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Affiliation(s)
- Jun Chen
- Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
- Center for Chemical Biology and Drug Discovery, Laboratory of Computational Biomedicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Di Zhang
- Center for Chemical Biology and Drug Discovery, Laboratory of Computational Biomedicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Lin-Ping Wu
- Center for Chemical Biology and Drug Discovery, Laboratory of Computational Biomedicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Ming Zhao
- Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
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18
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A Drop-on-Demand Bioprinting Approach to Spatially Arrange Multiple Cell Types and Monitor Their Cell-Cell Interactions towards Vascularization Based on Endothelial Cells and Mesenchymal Stem Cells. Cells 2023; 12:cells12040646. [PMID: 36831313 PMCID: PMC9953911 DOI: 10.3390/cells12040646] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/09/2023] [Accepted: 02/12/2023] [Indexed: 02/22/2023] Open
Abstract
Spheroids, organoids, or cell-laden droplets are often used as building blocks for bioprinting, but so far little is known about the spatio-temporal cellular interactions subsequent to printing. We used a drop-on-demand bioprinting approach to study the biological interactions of such building blocks in dimensions of micrometers. Highly-density droplets (approximately 700 cells in 10 nL) of multiple cell types were patterned in a 3D hydrogel matrix with a precision of up to 70 μm. The patterns were used to investigate interactions of endothelial cells (HUVECs) and adipose-derived mesenchymal stem cells (ASCs), which are related to vascularization. We demonstrated that a gap of 200 μm between HUVEC and ASC aggregates led to decreased sprouting of HUVECs towards ASCs and increased growth from ASCs towards HUVECs. For mixed aggregates containing both cell types, cellular interconnections of ASCs with lengths of up to approximately 800 µm and inhibition of HUVEC sprouting were observed. When ASCs were differentiated into smooth muscle cells (dASCs), separate HUVEC aggregates displayed decreased sprouting towards dASCs, whereas no cellular interconnections nor inhibition of HUVEC sprouting were detected for mixed dASCs/HUVEC aggregates. These findings demonstrate that our approach could be applied to investigate cell-cell interactions of different cell types in 3D co-cultures.
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19
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Building a 3D “bronchioid” to model chronic obstructive pulmonary disease (COPD). Rev Mal Respir 2023. [DOI: 10.1016/j.rmr.2022.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
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20
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Zhang S, Qi C, Zhang W, Zhou H, Wu N, Yang M, Meng S, Liu Z, Kong T. In Situ Endothelialization of Free-Form 3D Network of Interconnected Tubular Channels via Interfacial Coacervation by Aqueous-in-Aqueous Embedded Bioprinting. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2209263. [PMID: 36448877 DOI: 10.1002/adma.202209263] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 11/24/2022] [Indexed: 06/17/2023]
Abstract
The challenge of bioprinting vascularized tissues is structure retention and in situ endothelialization. The issue is addressed by adopting an aqueous-in-aqueous 3D embedded bioprinting strategy, in which the interfacial coacervation of the cyto-mimic aqueous two-phase systems (ATPS) are employed for maintaining the suspending liquid architectures, and serving as filamentous scaffolds for cell attachment and growth. By incorporating endothelial cells in the ink phase of ATPS, tubular lumens enclosed by coacervated complexes of polylysine (PLL) and oxidized bacteria celluloses (oxBC) can be cellularized with a confluent endothelial layer, without any help of adhesive peptides. By applying PLL/oxBC ATPS for embedded bioprinting, free-form 3D vascular networks with in situ endothelialization of interconnected tubular lumens are achieved. This simple approach is a one-step process without any sacrificed templates and post-treatments. The resultant functional vessel networks with arbitrary complexity are suspended in liquid medium and can be conveniently handled, opening new routes for the in vitro production of thick vascularized tissues for pathological research, regeneration therapy and animal-free drug development.
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Affiliation(s)
- Shanshan Zhang
- Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Cheng Qi
- College of Mechatronics and Control Engineering, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Wei Zhang
- Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Hui Zhou
- Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Nihuan Wu
- Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Ming Yang
- Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Si Meng
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Zhou Liu
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong, 518000, China
| | - Tiantian Kong
- Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong, 518000, China
- Department of Urology, Inst Translat Med, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518000, China
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21
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Gehlen J, Qiu W, Schädli GN, Müller R, Qin XH. Tomographic volumetric bioprinting of heterocellular bone-like tissues in seconds. Acta Biomater 2023; 156:49-60. [PMID: 35718102 DOI: 10.1016/j.actbio.2022.06.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/24/2022] [Accepted: 06/09/2022] [Indexed: 01/18/2023]
Abstract
Tomographic volumetric bioprinting (VBP) has recently emerged as a powerful tool for rapid solidification of cell-laden hydrogel constructs within seconds. However, its practical applications in tissue engineering requires a detailed understanding of how different printing parameters (concentration of resins, laser dose) affect cell activity and tissue formation. Herein, we explore a new application of VBP in bone tissue engineering by merging a soft gelatin methacryloyl (GelMA) bioresin (<5 kPa) with 3D endothelial co-culture to generate heterocellular bone-like constructs with enhanced functionality. To this, a series of bioresins with varying concentrations of GelMA and lithium Phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP) photoinitiator were formulated and characterized in terms of photo-reactivity, printability and cell-compatibility. A bioresin with 5% GelMA and 0.05% LAP was identified as the optimal formulation for VBP of complex perfusable constructs within 30 s at high cell viability (>90%). The fidelity was validated by micro-computed tomography and confocal microscopy. Compared to 10% GelMA, this bioresin provided a softer and more permissive environment for osteogenic differentiation of human mesenchymal stem cells (hMSCs). The expression of osteoblastic markers (collagen-I, ALP, osteocalcin) and osteocytic markers (podoplanin, Dmp1) was monitored for 42 days. After 21 days, early osteocytic markers were significantly increased in 3D co-cultures of hMSCs with human umbilical vein endothelial cells (HUVECs). Additionally, we demonstrate VBP of a perfusable, pre-vascularized model where HUVECs self-organized into an endothelium-lined channel. Altogether, this work leverages the benefits of VBP and 3D co-culture, offering a promising platform for fast scaled biofabrication of 3D bone-like tissues with unprecedented functionality. STATEMENT OF SIGNIFICANCE: This study explores new strategies for ultrafast bio-manufacturing of bone tissue models by leveraging the advantages of tomographic volumetric bioprinting (VBP) and endothelial co-culture. After screening the properties of a series of photocurable gelatin methacryloyl (GelMA) bioresins, a formulation with 5% GelMA was identified with optimal printability and permissiveness for osteogenic differentiation of human mesenchymal stem cells (hMSC). We then established 3D endothelial co-cultures to test if the heterocellular interactions may enhance the osteogenic differentiation in the printed environments. This hypothesis was evidenced by increased gene expression of early osteocytic markers in 3D co-cultures after 21 days. Finally, VBP of a perfusable cell-laden tissue construct is demonstrated for future applications in vascularized tissue engineering.
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Affiliation(s)
- Jenny Gehlen
- Institute for Biomechanics, ETH Zürich, Leopold-Ruzicka-Weg 4, 8093 Zürich, Switzerland
| | - Wanwan Qiu
- Institute for Biomechanics, ETH Zürich, Leopold-Ruzicka-Weg 4, 8093 Zürich, Switzerland
| | - Gian Nutal Schädli
- Institute for Biomechanics, ETH Zürich, Leopold-Ruzicka-Weg 4, 8093 Zürich, Switzerland
| | - Ralph Müller
- Institute for Biomechanics, ETH Zürich, Leopold-Ruzicka-Weg 4, 8093 Zürich, Switzerland
| | - Xiao-Hua Qin
- Institute for Biomechanics, ETH Zürich, Leopold-Ruzicka-Weg 4, 8093 Zürich, Switzerland.
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22
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Yuan Y. Clinical Translation of Engineered Pulmonary Vascular Models. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1413:273-288. [PMID: 37195536 DOI: 10.1007/978-3-031-26625-6_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
Diseases in pulmonary vasculature remain a major cause of morbidity and mortality worldwide. Numerous pre-clinical animal models were developed to understand lung vasculature during diseases and development. However, these systems are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. In recent years, a growing number of studies have focused on developing in vitro experimental platforms that mimic human tissues/organs. In this chapter, we discuss the key components involved in developing engineered pulmonary vascular modeling systems and provide perspectives on ways to improve the translational potential of existing models.
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Affiliation(s)
- Yifan Yuan
- Department of Medicine (Pulmonary), Department of Anesthesiology, Yale University, New Haven, CT, USA.
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23
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Kamaraj M, Giri PS, Mahapatra S, Pati F, Rath SN. Bioengineering strategies for 3D bioprinting of tubular construct using tissue-specific decellularized extracellular matrix. Int J Biol Macromol 2022; 223:1405-1419. [PMID: 36375675 DOI: 10.1016/j.ijbiomac.2022.11.064] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 11/02/2022] [Accepted: 11/07/2022] [Indexed: 11/13/2022]
Abstract
The goal of the current study is to develop an extracellular matrix bioink that could mimic the biochemical components present in natural blood vessels. Here, we have used an innovative approach to recycle the discarded varicose vein for isolation of endothelial cells and decellularization of the same sample to formulate the decellularized extracellular matrix (dECM) bioink. The shift towards dECM bioink observed as varicose vein dECM provides the tissue-specific biochemical factors that will enhance the regeneration capability. Interestingly, the encapsulated umbilical cord mesenchymal stem cells expressed the markers of vascular smooth muscle cells because of the cues present in the vein dECM. Further, in vitro immunological investigation of dECM revealed a predominant M2 polarization which could further aid in tissue remodeling. A novel approach was used to fabricate vascular construct using 3D bioprinting without secondary support. The outcomes suggest that this could be a potential approach for patient- and tissue-specific blood vessel regeneration.
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Affiliation(s)
- Meenakshi Kamaraj
- Regenerative Medicine and Stem cell (RMS) Laboratory, Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Telangana, India
| | - Pravin Shankar Giri
- Regenerative Medicine and Stem cell (RMS) Laboratory, Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Telangana, India
| | - Sandeep Mahapatra
- Vascular & Endovascular Surgery, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Falguni Pati
- BioFabTE Lab, Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Telangana, India
| | - Subha Narayan Rath
- Regenerative Medicine and Stem cell (RMS) Laboratory, Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Telangana, India.
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24
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Rojek K, Ćwiklińska M, Kuczak J, Guzowski J. Microfluidic Formulation of Topological Hydrogels for Microtissue Engineering. Chem Rev 2022; 122:16839-16909. [PMID: 36108106 PMCID: PMC9706502 DOI: 10.1021/acs.chemrev.1c00798] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Indexed: 02/07/2023]
Abstract
Microfluidics has recently emerged as a powerful tool in generation of submillimeter-sized cell aggregates capable of performing tissue-specific functions, so-called microtissues, for applications in drug testing, regenerative medicine, and cell therapies. In this work, we review the most recent advances in the field, with particular focus on the formulation of cell-encapsulating microgels of small "dimensionalities": "0D" (particles), "1D" (fibers), "2D" (sheets), etc., and with nontrivial internal topologies, typically consisting of multiple compartments loaded with different types of cells and/or biopolymers. Such structures, which we refer to as topological hydrogels or topological microgels (examples including core-shell or Janus microbeads and microfibers, hollow or porous microstructures, or granular hydrogels) can be precisely tailored with high reproducibility and throughput by using microfluidics and used to provide controlled "initial conditions" for cell proliferation and maturation into functional tissue-like microstructures. Microfluidic methods of formulation of topological biomaterials have enabled significant progress in engineering of miniature tissues and organs, such as pancreas, liver, muscle, bone, heart, neural tissue, or vasculature, as well as in fabrication of tailored microenvironments for stem-cell expansion and differentiation, or in cancer modeling, including generation of vascularized tumors for personalized drug testing. We review the available microfluidic fabrication methods by exploiting various cross-linking mechanisms and various routes toward compartmentalization and critically discuss the available tissue-specific applications. Finally, we list the remaining challenges such as simplification of the microfluidic workflow for its widespread use in biomedical research, bench-to-bedside transition including production upscaling, further in vivo validation, generation of more precise organ-like models, as well as incorporation of induced pluripotent stem cells as a step toward clinical applications.
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Affiliation(s)
- Katarzyna
O. Rojek
- Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - Monika Ćwiklińska
- Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - Julia Kuczak
- Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - Jan Guzowski
- Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
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25
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Wang D, Maharjan S, Kuang X, Wang Z, Mille LS, Tao M, Yu P, Cao X, Lian L, Lv L, He JJ, Tang G, Yuk H, Ozaki CK, Zhao X, Zhang YS. Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels. SCIENCE ADVANCES 2022; 8:eabq6900. [PMID: 36288300 PMCID: PMC9604524 DOI: 10.1126/sciadv.abq6900] [Citation(s) in RCA: 75] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 08/17/2022] [Indexed: 05/03/2023]
Abstract
Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The tough hydrogel consisted of energy-dissipative ionically cross-linked alginate and elastic enzyme-cross-linked gelatin. The 3D bioprinted venous and arterial conduits exhibited key functionalities of respective vessels including relevant mechanical properties, perfusability, barrier performance, expressions of specific markers, and susceptibility to severe acute respiratory syndrome coronavirus 2 pseudo-viral infection. Notably, the arterial conduits revealed physiological vasoconstriction and vasodilatation responses. We further explored the feasibility of these conduits for vascular anastomosis. Together, our study presents biofabrication of mechanically and functionally relevant vascular conduits, showcasing their potentials as vascular models for disease studies in vitro and as grafts for vascular surgeries in vivo, possibly serving broad biomedical applications in the future.
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Affiliation(s)
- Di Wang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
- Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P. R. China
| | - Sushila Maharjan
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Xiao Kuang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Zixuan Wang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Luis S. Mille
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Ming Tao
- Department of Surgery and the Heart and Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Peng Yu
- Department of Surgery and the Heart and Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Xia Cao
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Liming Lian
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Li Lv
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Jacqueline Jialu He
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Guosheng Tang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
| | - Hyunwoo Yuk
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - C. Keith Ozaki
- Department of Surgery and the Heart and Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Xuanhe Zhao
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Yu Shrike Zhang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
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26
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Terrassoux L, Claux H, Bacari S, Meignan S, Furlan A. A Bloody Conspiracy. Blood Vessels and Immune Cells in the Tumor Microenvironment. Cancers (Basel) 2022; 14:cancers14194581. [PMID: 36230504 PMCID: PMC9558972 DOI: 10.3390/cancers14194581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/10/2022] [Accepted: 09/15/2022] [Indexed: 11/29/2022] Open
Abstract
Simple Summary The tumor microenvironment has risen over the last years as a significant contributor to the failure of antitumoral strategies due to its numerous pro-tumorigenic activities. In this review, we focused on two features of this microenvironment, namely angiogenesis and immunity, which have been the targets of therapies to tackle tumors via its microenvironmental part over the last decade. Increasing our knowledge of the complex interactions within this ecosystem is mandatory to optimize these therapeutic approaches. The development of innovative experimental models is of great help in reaching this goal. Abstract Cancer progression occurs in concomitance with a profound remodeling of the cellular microenvironment. Far from being a mere passive event, the re-orchestration of interactions between the various cell types surrounding tumors highly contributes to the progression of the latter. Tumors notably recruit and stimulate the sprouting of new blood vessels through a process called neo-angiogenesis. Beyond helping the tumor cope with an increased metabolic demand associated with rapid growth, this also controls the metastatic dissemination of cancer cells and the infiltration of immune cells in the tumor microenvironment. To decipher this critical interplay for the clinical progression of tumors, the research community has developed several valuable models in the last decades. This review offers an overview of the various instrumental solutions currently available, including microfluidic chips, co-culture models, and the recent rise of organoids. We highlight the advantages of each technique and the specific questions they can address to better understand the tumor immuno-angiogenic ecosystem. Finally, we discuss this development field’s fundamental and applied perspectives.
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Affiliation(s)
- Lisa Terrassoux
- Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France
- Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, F-59000 Lille, France
| | - Hugo Claux
- Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France
- Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, F-59000 Lille, France
| | - Salimata Bacari
- Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France
- Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, F-59000 Lille, France
| | - Samuel Meignan
- Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France
- Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, F-59000 Lille, France
| | - Alessandro Furlan
- Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France
- Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, F-59000 Lille, France
- Correspondence:
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27
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Wang S, Zhao Q, Li J, Du X. Morphing-to-Adhesion Polysaccharide Hydrogel for Adaptive Biointerfaces. ACS APPLIED MATERIALS & INTERFACES 2022; 14:42420-42429. [PMID: 36083279 DOI: 10.1021/acsami.2c10117] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Reliable functions of medical implants highly depend on biocompatible, conformal, and stable biointerfaces for seamless biointegration with biological tissues. Though flexible biointerfaces based on synthetic hydrogels have shown promise in optimizing implant biointegration via surgical suturing, physical attachment, or manual preshaping, they still suffer from poor adaptability, such as tissue damage by surgical suturing, low bioactivity, and difficulties in conformal contact and stable fixation, especially for specific tissues of large surface curvatures. Here, we report a bilayer hydrogel-based adaptive biointerface (HAB) made of two polysaccharide derivates, N-hydroxysuccinimide (NHS) ester-activated alginate and chitosan, harnessing dual advantages of their different swelling and active groups. Leveraging on the differential swelling between the two hydrogel layers and covalent linkages with active groups at hydrogel interfaces, HABs can be programmed into sealed tubes with tunable diameters via water-induced compliable shape morphing and instant interfacial adhesion. We further demonstrate that the polysaccharide-based morphing-to-adhesion HAB possesses outstanding bioactivity in directing cellular focal adhesion and intercellular junction, versatile geometrical adaptability to diverse tubular tissues with a wide range of surface curvatures (2.8 × 102-1.3 × 103 m-1), and excellent mechanical stability in high load-/shear-bearing physiological environments (blood flow volume: 85 mm·s-1). HABs overcome the limitations of existing biointerfaces in terms of poor bioactivity and difficult biointegration with biological tissues of large surface curvatures, holding promise to open new avenues for adaptive biointerfaces and reliable medical implants.
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Affiliation(s)
- Shanshan Wang
- Institute of Biomedical & Health Engineering, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518035, China
- Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 100083, China
| | - Qilong Zhao
- Institute of Biomedical & Health Engineering, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518035, China
| | - Jinhong Li
- Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 100083, China
| | - Xuemin Du
- Institute of Biomedical & Health Engineering, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518035, China
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28
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Hu X, Zheng J, Hu Q, Liang L, Yang D, Cheng Y, Li SS, Chen LJ, Yang Y. Smart acoustic 3D cell construct assembly with high-resolution. Biofabrication 2022; 14. [PMID: 35764072 DOI: 10.1088/1758-5090/ac7c90] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 06/22/2022] [Indexed: 11/12/2022]
Abstract
Precise and flexible three-dimensional (3D) cell construct assembly using external forces or fields can produce micro-scale cellular architectures with intercellular connections, which is an important prerequisite to reproducing the structures and functions of biological systems. Currently, it is also a substantial challenge in the bioengineering field. Here, we propose a smart acoustic 3D cell assembly strategy that utilizes a 3D printed module and hydrogel sheets. Digitally controlled six wave beams offer a high degree of freedom (including wave vector combination, frequency, phase, and amplitude) that enables versatile biomimetic micro cellular patterns in hydrogel sheets. Further, replaceable frames can be used to fix the acoustic-built micro-scale cellular structures in these sheets, enabling user-defined hierarchical or heterogeneous constructs through layer-by-layer assembly. This strategy can be employed to construct vasculature with different diameters and lengths, composed of human umbilical vein endothelial cells and smooth muscle cells. These constructs can also induce controllable vascular network formation. Overall, the findings of this work extend the capabilities of acoustic cell assembly into 3D space, offering advantages including innovative, flexible, and precise patterning, and displaying great potential for the manufacture of various artificial tissue structures that duplicate in vivo functions.
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Affiliation(s)
- Xuejia Hu
- School of Electronic Science and Engineering, Xiamen University, Xiamen University, No. 422 Siming south road, Xiamen, Fujian, 361005, CHINA
| | - Jingjing Zheng
- School of physics and engineering, Wuhan University, luojia mountain street, Wuhan, Wuhan, Hubei, 430072, CHINA
| | - Qinghao Hu
- School of physics and engineering, Wuhan University, luojia street, Wuhan, Wuhan, Hubei, 430072, CHINA
| | - Li Liang
- School of Physics and Electronic Technology, Anhui Normal University, No. 189 of jiuhua south road, Wuhu, Wuhu, Anhui, 241000, CHINA
| | - Dongyong Yang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, No. 238, Jiefang road, Wuhan, Hubei, 430060, CHINA
| | - Yanxiang Cheng
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, No. 238, Jiefang road, Wuhan, Hubei, 430060, CHINA
| | - Sen-Sen Li
- School of Electronic Science and Engineering, Xiamen University, Xiamen University, No. 422 Siming south road, Xiamen, Fujian, 361005, CHINA
| | - Lu-Jian Chen
- School of Electronic Science and Engineering, Xiamen University, Xiamen University, No. 422 Siming south road, Xiamen, Fujian, 361005, CHINA
| | - Yi Yang
- School of physics and engineering, Wuhan University, luojia street, Wuhan, Wuhan, Hubei, 430072, CHINA
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29
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Biofabrication of Collagen Tissue-Engineered Blood Vessels with Direct Co-Axial Extrusion. Int J Mol Sci 2022; 23:ijms23105618. [PMID: 35628424 PMCID: PMC9144639 DOI: 10.3390/ijms23105618] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 05/14/2022] [Accepted: 05/16/2022] [Indexed: 02/04/2023] Open
Abstract
Cardiovascular diseases are considered one of the worldwide causes of death, with atherosclerosis being the most predominant. Nowadays, the gold standard treatment is blood vessel replacement by bypass surgery; however, autologous source is not always possible. Thereby, tissue-engineered blood vessels (TEBVs) are emerging as a potential alternative source. In terms of composition, collagen has been selected in many occasions to develop TEBVs as it is one of the main extracellular matrix components of arteries. However, it requires specific support or additional processing to maintain the tubular structure and appropriate mechanical properties. Here, we present a method to develop support-free collagen TEBVs with co-axial extrusion in a one-step procedure with high concentrated collagen. The highest concentration of collagen of 20 mg/mL presented a burst pressure of 619.55 ± 48.77 mmHg, being able to withstand perfusion of 10 dynes/cm2. Viability results showed a high percentage of viability (86.1 and 85.8% with 10 and 20 mg/mL, respectively) of human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVEC) after 24 h extrusion. Additionally, HUVEC and HASMCs were mainly localized in their respective layers, mimicking the native distribution. All in all, this approach allows the direct extrusion of collagen TEBVs in a one-step procedure with enough mechanical properties to be perfused.
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30
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Aydin O, Passaro AP, Raman R, Spellicy SE, Weinberg RP, Kamm RD, Sample M, Truskey GA, Zartman J, Dar RD, Palacios S, Wang J, Tordoff J, Montserrat N, Bashir R, Saif MTA, Weiss R. Principles for the design of multicellular engineered living systems. APL Bioeng 2022; 6:010903. [PMID: 35274072 PMCID: PMC8893975 DOI: 10.1063/5.0076635] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 02/02/2022] [Indexed: 12/14/2022] Open
Abstract
Remarkable progress in bioengineering over the past two decades has enabled the formulation of fundamental design principles for a variety of medical and non-medical applications. These advancements have laid the foundation for building multicellular engineered living systems (M-CELS) from biological parts, forming functional modules integrated into living machines. These cognizant design principles for living systems encompass novel genetic circuit manipulation, self-assembly, cell-cell/matrix communication, and artificial tissues/organs enabled through systems biology, bioinformatics, computational biology, genetic engineering, and microfluidics. Here, we introduce design principles and a blueprint for forward production of robust and standardized M-CELS, which may undergo variable reiterations through the classic design-build-test-debug cycle. This Review provides practical and theoretical frameworks to forward-design, control, and optimize novel M-CELS. Potential applications include biopharmaceuticals, bioreactor factories, biofuels, environmental bioremediation, cellular computing, biohybrid digital technology, and experimental investigations into mechanisms of multicellular organisms normally hidden inside the "black box" of living cells.
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Affiliation(s)
| | - Austin P. Passaro
- Regenerative Bioscience Center, University of Georgia, Athens, Georgia 30602, USA
| | - Ritu Raman
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | | | - Robert P. Weinberg
- School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts 02115, USA
| | | | - Matthew Sample
- Center for Ethics and Law in the Life Sciences, Leibniz Universität Hannover, 30167 Hannover, Germany
| | - George A. Truskey
- Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA
| | - Jeremiah Zartman
- Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, USA
| | - Roy D. Dar
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
| | - Sebastian Palacios
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA
| | - Jason Wang
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
| | - Jesse Tordoff
- Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | - Nuria Montserrat
- Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
| | | | - M. Taher A. Saif
- Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
| | - Ron Weiss
- Author to whom correspondence should be addressed:
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31
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Recher G, Mombereau A, Boyreau A, Nassoy P, Andrique L. [3D Tumor organoid models produced by cellular capsules technology CCT]. Bull Cancer 2022; 109:38-48. [PMID: 34996600 DOI: 10.1016/j.bulcan.2021.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/28/2021] [Accepted: 12/03/2021] [Indexed: 10/19/2022]
Abstract
Monolayer cultures of cell lines and derived-patient cells have long been the in vitro model of choice in oncology. In particular, these models have made it possible to decipher the mechanisms that determine tumor proliferation and invasion. However these 2D models are insufficient because they do not take into account the spatial organization of cells and their interactions with each other or with the extracellular matrix. In the context of cancer, there is a need to develop new 3D (tumoroid) models in order to gain a better understanding of the development of these pathologies but also to assess the penetration of drugs through a tissue and the associated cellular response. We present here the cell capsule technology (CCT), which allows the production of different tumoroid models: simple or more complex 3D culture models including co-culture of tumor cells with components of the microenvironment (fibroblasts, matrix, etc.). The development of these new 3D culture systems now makes it possible to propose refined physiopathological models that will allow the implementation of improved targeted therapeutic strategies.
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Affiliation(s)
- Gaëlle Recher
- Université de Bordeaux, Laboratoire photonique numérique et nanosciences, UMR 5298, 33400 Talence, France; Institut d'optique & Centre national de la recherche scientifique, LP2N, UMR 5298, 33400 Talence, France
| | - Amaël Mombereau
- Université de Bordeaux, Laboratoire photonique numérique et nanosciences, UMR 5298, 33400 Talence, France; Institut d'optique & Centre national de la recherche scientifique, LP2N, UMR 5298, 33400 Talence, France
| | - Adeline Boyreau
- Université de Bordeaux, Laboratoire photonique numérique et nanosciences, UMR 5298, 33400 Talence, France; Institut d'optique & Centre national de la recherche scientifique, LP2N, UMR 5298, 33400 Talence, France
| | - Pierre Nassoy
- Université de Bordeaux, Laboratoire photonique numérique et nanosciences, UMR 5298, 33400 Talence, France; Institut d'optique & Centre national de la recherche scientifique, LP2N, UMR 5298, 33400 Talence, France
| | - Laëtitia Andrique
- Plateforme VoxCell, UMS TBMcore 3427, 146 rue Léo-Saignat, Bâtiment 1A 2(e) étage, 33076 Bordeaux, France.
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32
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Selahi A, Fernando T, Chakraborty S, Muthuchamy M, Zawieja DC, Jain A. Lymphangion-chip: a microphysiological system which supports co-culture and bidirectional signaling of lymphatic endothelial and muscle cells. LAB ON A CHIP 2021; 22:121-135. [PMID: 34850797 PMCID: PMC9761984 DOI: 10.1039/d1lc00720c] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
The pathophysiology of several lymphatic diseases, such as lymphedema, depends on the function of lymphangions that drive lymph flow. Even though the signaling between the two main cellular components of a lymphangion, endothelial cells (LECs) and muscle cells (LMCs), is responsible for crucial lymphatic functions, there are no in vitro models that have included both cell types. Here, a fabrication technique (gravitational lumen patterning or GLP) is developed to create a lymphangion-chip. This organ-on-chip consists of co-culture of a monolayer of endothelial lumen surrounded by multiple and uniformly thick layers of muscle cells. The platform allows construction of a wide range of luminal diameters and muscular layer thicknesses, thus providing a toolbox to create variable anatomy. In this device, lymphatic muscle cells align circumferentially while endothelial cells aligned axially under flow, as only observed in vivo in the past. This system successfully characterizes the dynamics of cell size, density, growth, alignment, and intercellular gap due to co-culture and shear. Finally, exposure to pro-inflammatory cytokines reveals that the device could facilitate the regulation of endothelial barrier function through the lymphatic muscle cells. Therefore, this bioengineered platform is suitable for use in preclinical research of lymphatic and blood mechanobiology, inflammation, and translational outcomes.
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Affiliation(s)
- Amirali Selahi
- Department of Biomedical Engineering, College of Engineering, Texas A&M University, 101 Bizzell Street College Station, TX, 77843, USA.
| | - Teshan Fernando
- Department of Biomedical Engineering, College of Engineering, Texas A&M University, 101 Bizzell Street College Station, TX, 77843, USA.
| | - Sanjukta Chakraborty
- Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Bryan, TX, USA
| | - Mariappan Muthuchamy
- Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Bryan, TX, USA
| | - David C Zawieja
- Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Bryan, TX, USA
| | - Abhishek Jain
- Department of Biomedical Engineering, College of Engineering, Texas A&M University, 101 Bizzell Street College Station, TX, 77843, USA.
- Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Bryan, TX, USA
- Department of Cardiovascular Sciences, Houston Methodist Academic Institute, Houston, TX, USA
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Sun B, Hou L, Sun B, Han Y, Zou Y, Huang J, Zhang Y, Feng C, Dou X, Xu F. Use of Electrospun Phenylalanine/Poly-ε-Caprolactone Chiral Hybrid Scaffolds to Promote Endothelial Remodeling. Front Bioeng Biotechnol 2021; 9:773635. [PMID: 34900965 PMCID: PMC8656108 DOI: 10.3389/fbioe.2021.773635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 10/27/2021] [Indexed: 02/02/2023] Open
Abstract
The fabrication of tissue-engineered vascular grafts to replace damaged vessels is a promising therapy for cardiovascular diseases. Endothelial remodeling in the lumen of TEVGs is critical for successful revascularization. However, the construction of well-functioning TEVGs remains a fundamental challenge. Herein, chiral hybrid scaffolds were prepared by electrospinning using D/L-phenylalanine based gelators [D(L)PHEG] and poly-ε-caprolactone (PCL). The chirality of scaffolds significantly affected the endothelial remodeling progress of TEVGs. Compared with L-phenylalanine based gelators/poly-ε-caprolactone (L/PCL) and PCL, D-phenylalanine based gelators/poly-ε-caprolactone (D/PCL) scaffolds enhanced cell adhesion, and proliferation and upregulated the expression of fibronectin-1, and vinculin. These results suggests that chiral hybrid scaffolds can promote endothelial remodeling of TEVGs by upregulating adhesion-associated protein levels. This study offers an innovative strategy for endothelial remodeling of TEVGs by fabricating chiral hybrid scaffolds, and provides new insight for the treatment of cardiovascular diseases.
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Affiliation(s)
- Benlin Sun
- Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, China
| | - Lei Hou
- Department of Cardiology, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Binbin Sun
- Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Han
- Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yunqing Zou
- State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Juexin Huang
- State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yanan Zhang
- Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, China
| | - Chuanliang Feng
- State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoqiu Dou
- State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Feng Xu
- Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, China.,Department of Subject Planning Shanghai, Ninth People's Hospital Shanghai, Jiao Tong University School of Medicine, Shanghai, China
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34
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Varrone F, Mandrich L, Caputo E. Melanoma Immunotherapy and Precision Medicine in the Era of Tumor Micro-Tissue Engineering: Where Are We Now and Where Are We Going? Cancers (Basel) 2021; 13:5788. [PMID: 34830940 PMCID: PMC8616100 DOI: 10.3390/cancers13225788] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/05/2021] [Accepted: 11/12/2021] [Indexed: 11/16/2022] Open
Abstract
Malignant melanoma still remains a cancer with very poor survival rates, although it is at the forefront of personalized medicine. Most patients show partial responses and disease progressed due to adaptative resistance mechanisms, preventing long-lasting clinical benefits to the current treatments. The response to therapies can be shaped by not only taking into account cancer cell heterogeneity and plasticity, but also by its structural context as well as the cellular component of the tumor microenvironment (TME). Here, we review the recent development in the field of immunotherapy and target-based therapy and how, in the era of tumor micro-tissue engineering, ex-vivo assays could help to enhance our melanoma biology knowledge in its complexity, translating it in the development of successful therapeutic strategies, as well as in the prediction of therapeutic benefits.
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Affiliation(s)
| | - Luigi Mandrich
- Research Institute on Terrestrial Ecosystem—IRET-CNR Via Pietro Castellino 111, I-80131 Naples, Italy;
| | - Emilia Caputo
- Institute of Genetics and Biophysics—IGB-CNR, “A. Buzzati-Traverso”, Via Pietro Castellino 111, I-80131 Naples, Italy
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35
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Construction and evaluation of co-electrospun poly (butylene succinate)/gelatin materials as potential vascular grafts. Chin J Chem Eng 2021. [DOI: 10.1016/j.cjche.2021.06.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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36
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Vella G, Guelfi S, Bergers G. High Endothelial Venules: A Vascular Perspective on Tertiary Lymphoid Structures in Cancer. Front Immunol 2021; 12:736670. [PMID: 34484246 PMCID: PMC8416033 DOI: 10.3389/fimmu.2021.736670] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 07/30/2021] [Indexed: 01/22/2023] Open
Abstract
High endothelial venules (HEVs) are specialized postcapillary venules composed of cuboidal blood endothelial cells that express high levels of sulfated sialomucins to bind L-Selectin/CD62L on lymphocytes, thereby facilitating their transmigration from the blood into the lymph nodes (LN) and other secondary lymphoid organs (SLO). HEVs have also been identified in human and murine tumors in predominantly CD3+T cell-enriched areas with fewer CD20+B-cell aggregates that are reminiscent of tertiary lymphoid-like structures (TLS). While HEV/TLS areas in human tumors are predominantly associated with increased survival, tumoral HEVs (TU-HEV) in mice have shown to foster lymphocyte-enriched immune centers and boost an immune response combined with different immunotherapies. Here, we discuss the current insight into TU-HEV formation, function, and regulation in tumors and elaborate on the functional implication, opportunities, and challenges of TU-HEV formation for cancer immunotherapy.
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Affiliation(s)
- Gerlanda Vella
- Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, Vlaams Instituut voor Biotechnologie (VIB)-Center for Cancer Biology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium
| | - Sophie Guelfi
- Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, Vlaams Instituut voor Biotechnologie (VIB)-Center for Cancer Biology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium
| | - Gabriele Bergers
- Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, Vlaams Instituut voor Biotechnologie (VIB)-Center for Cancer Biology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.,Department of Neurological Surgery, UCSF Comprehensive Cancer Center, University of California San Francisco (UCSF), San Francisco, CA, United States
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37
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Ebner-Peking P, Krisch L, Wolf M, Hochmann S, Hoog A, Vári B, Muigg K, Poupardin R, Scharler C, Schmidhuber S, Russe E, Stachelscheid H, Schneeberger A, Schallmoser K, Strunk D. Self-assembly of differentiated progenitor cells facilitates spheroid human skin organoid formation and planar skin regeneration. Theranostics 2021; 11:8430-8447. [PMID: 34373751 PMCID: PMC8344006 DOI: 10.7150/thno.59661] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 07/02/2021] [Indexed: 01/01/2023] Open
Abstract
Self-assembly of solid organs from single cells would greatly expand applicability of regenerative medicine. Stem/progenitor cells can self-organize into micro-sized organ units, termed organoids, partially modelling tissue function and regeneration. Here we demonstrated 3D self-assembly of adult and induced pluripotent stem cell (iPSC)-derived fibroblasts, keratinocytes and endothelial progenitors into both, planar human skin in vivo and a novel type of spheroid-shaped skin organoids in vitro, under the aegis of human platelet lysate. Methods: Primary endothelial colony forming cells (ECFCs), skin fibroblasts (FBs) and keratinocytes (KCs) were isolated from human tissues and polyclonally propagated under 2D xeno-free conditions. Human tissue-derived iPSCs were differentiated into endothelial cells (hiPSC-ECs), fibroblasts (hiPSC-FBs) and keratinocytes (hiPSC-KCs) according to efficiency-optimized protocols. Cell identity and purity were confirmed by flow cytometry and clonogenicity indicated their stem/progenitor potential. Triple cell type floating spheroids formation was promoted by human platelet-derived growth factors containing culture conditions, using nanoparticle cell labelling for monitoring the organization process. Planar human skin regeneration was assessed in full-thickness wounds of immune-deficient mice upon transplantation of hiPSC-derived single cell suspensions. Results: Organoids displayed a distinct architecture with surface-anchored keratinocytes surrounding a stromal core, and specific signaling patterns in response to inflammatory stimuli. FGF-7 mRNA transfection was required to accelerate keratinocyte long-term fitness. Stratified human skin also self-assembled within two weeks after either adult- or iPSC-derived skin cell-suspension liquid-transplantation, healing deep wounds of mice. Transplant vascularization significantly accelerated in the presence of co-transplanted endothelial progenitors. Mechanistically, extracellular vesicles mediated the multifactorial platelet-derived trophic effects. No tumorigenesis occurred upon xenografting. Conclusion: This illustrates the superordinate progenitor self-organization principle and permits novel rapid 3D skin-related pharmaceutical high-content testing opportunities with floating spheroid skin organoids. Multi-cell transplant self-organization facilitates development of iPSC-based organ regeneration strategies using cell suspension transplantation supported by human platelet factors.
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Affiliation(s)
- Patricia Ebner-Peking
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Linda Krisch
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
- Department of Transfusion Medicine, University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Martin Wolf
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Sarah Hochmann
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Anna Hoog
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Balázs Vári
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Katharina Muigg
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Rodolphe Poupardin
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Cornelia Scharler
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
| | | | - Elisabeth Russe
- Department of Plastic, Aesthetic and Reconstructive Surgery, Hospital Barmherzige Brueder, Salzburg, Austria
| | | | | | - Katharina Schallmoser
- Department of Transfusion Medicine, University Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Dirk Strunk
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), University Clinic, Paracelsus Medical University, Salzburg, Austria
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38
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Wu P, Xi X, Li R, Sun G. Engineering Polysaccharides for Tissue Repair and Regeneration. Macromol Biosci 2021; 21:e2100141. [PMID: 34219388 DOI: 10.1002/mabi.202100141] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 06/11/2021] [Indexed: 12/22/2022]
Abstract
The success of repair or regeneration depends greatly on the architecture of 3D scaffolds that finely mimic natural extracellular matrix to support cell growth and assembly. Polysaccharides have excellent biocompatibility with intrinsic biological cues and they have been extensively investigated as scaffolds for tissue engineering and regenerative medicine (TERM). The physical and biochemical structures of natural polysaccharides, however, can barely meet all the requirements of tissue-engineered scaffolds. To take advantage of their inherent properties, many innovative approaches including chemical, physical, or joint modifications have been employed to improve their properties. Recent advancement in molecular and material building technology facilitates the fabrication of advanced 3D structures with desirable properties. This review focuses on the latest progress of polysaccharide-based scaffolds for TERM, especially those that construct advanced architectures for tissue regeneration.
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Affiliation(s)
- Pingli Wu
- College of Chemistry and Environmental Science, Institute of Life Science and Green Development, Hebei University, Baoding, 071002, China
| | - Xin Xi
- Affiliated Hospital of Hebei University, College of Clinical Medicine, Institute of Life Science and Green Development, Hebei University, Baoding, 071000, China
| | - Ruochen Li
- College of Chemistry and Environmental Science, Institute of Life Science and Green Development, Hebei University, Baoding, 071002, China
| | - Guoming Sun
- College of Chemistry and Environmental Science, Institute of Life Science and Green Development, Hebei University, Baoding, 071002, China.,Affiliated Hospital of Hebei University, College of Clinical Medicine, Institute of Life Science and Green Development, Hebei University, Baoding, 071000, China
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39
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Wang P, Sun Y, Shi X, Shen H, Ning H, Liu H. Bioscaffolds embedded with regulatory modules for cell growth and tissue formation: A review. Bioact Mater 2021; 6:1283-1307. [PMID: 33251379 PMCID: PMC7662879 DOI: 10.1016/j.bioactmat.2020.10.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 10/07/2020] [Accepted: 10/21/2020] [Indexed: 02/06/2023] Open
Abstract
The demand for artificial organs has greatly increased because of various aging-associated diseases and the wide need for organ transplants. A recent trend in tissue engineering is the precise reconstruction of tissues by the growth of cells adhering to bioscaffolds, which are three-dimensional (3D) structures that guide tissue and organ formation. Bioscaffolds used to fabricate bionic tissues should be able to not only guide cell growth but also regulate cell behaviors. Common regulation methods include biophysical and biochemical stimulations. Biophysical stimulation cues include matrix hardness, external stress and strain, surface topology, and electromagnetic field and concentration, whereas biochemical stimulation cues include growth factors, proteins, kinases, and magnetic nanoparticles. This review discusses bioink preparation, 3D bioprinting (including extrusion-based, inkjet, and ultraviolet-assisted 3D bioprinting), and regulation of cell behaviors. In particular, it provides an overview of state-of-the-art methods and devices for regulating cell growth and tissue formation and the effects of biophysical and biochemical stimulations on cell behaviors. In addition, the fabrication of bioscaffolds embedded with regulatory modules for biomimetic tissue preparation is explained. Finally, challenges in cell growth regulation and future research directions are presented.
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Affiliation(s)
- Pengju Wang
- Department of Mechanical Manufacturing and Automation, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001, China
| | - Yazhou Sun
- Department of Mechanical Manufacturing and Automation, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001, China
| | - Xiaoquan Shi
- Department of Mechanical Manufacturing and Automation, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001, China
| | - Huixing Shen
- Department of Mechanical Manufacturing and Automation, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001, China
| | - Haohao Ning
- Department of Mechanical Manufacturing and Automation, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001, China
| | - Haitao Liu
- Department of Mechanical Manufacturing and Automation, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001, China
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40
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Browne S, Gill EL, Schultheiss P, Goswami I, Healy KE. Stem cell-based vascularization of microphysiological systems. Stem Cell Reports 2021; 16:2058-2075. [PMID: 33836144 PMCID: PMC8452487 DOI: 10.1016/j.stemcr.2021.03.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 03/11/2021] [Accepted: 03/15/2021] [Indexed: 12/27/2022] Open
Abstract
Microphysiological systems (MPSs) (i.e., tissue or organ chips) exploit microfluidics and 3D cell culture to mimic tissue and organ-level physiology. The advent of human induced pluripotent stem cell (hiPSC) technology has accelerated the use of MPSs to study human disease in a range of organ systems. However, in the reduction of system complexity, the intricacies of vasculature are an often-overlooked aspect of MPS design. The growing library of pluripotent stem cell-derived endothelial cell and perivascular cell protocols have great potential to improve the physiological relevance of vasculature within MPS, specifically for in vitro disease modeling. Three strategic categories of vascular MPS are outlined: self-assembled, interface focused, and 3D biofabricated. This review discusses key features and development of the native vasculature, linking that to how hiPSC-derived vascular cells have been generated, the state of the art in vascular MPSs, and opportunities arising from interdisciplinary thinking.
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Affiliation(s)
- Shane Browne
- Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA 94720, USA
| | - Elisabeth L Gill
- Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA 94720, USA
| | - Paula Schultheiss
- Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA 94720, USA
| | - Ishan Goswami
- Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA 94720, USA; Department of Materials Science and Engineering, University of California, Berkeley, CA 94720, USA
| | - Kevin E Healy
- Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA 94720, USA; Department of Materials Science and Engineering, University of California, Berkeley, CA 94720, USA.
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41
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Guyon J, Chapouly C, Andrique L, Bikfalvi A, Daubon T. The Normal and Brain Tumor Vasculature: Morphological and Functional Characteristics and Therapeutic Targeting. Front Physiol 2021; 12:622615. [PMID: 33746770 PMCID: PMC7973205 DOI: 10.3389/fphys.2021.622615] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 01/25/2021] [Indexed: 12/20/2022] Open
Abstract
Glioblastoma is among the most common tumor of the central nervous system in adults. Overall survival has not significantly improved over the last decade, even with optimizing standard therapeutic care including extent of resection and radio- and chemotherapy. In this article, we review features of the brain vasculature found in healthy cerebral tissue and in glioblastoma. Brain vessels are of various sizes and composed of several vascular cell types. Non-vascular cells such as astrocytes or microglia also interact with the vasculature and play important roles. We also discuss in vitro engineered artificial blood vessels which may represent useful models for better understanding the tumor-vessel interaction. Finally, we summarize results from clinical trials with anti-angiogenic therapy alone or in combination, and discuss the value of these approaches for targeting glioblastoma.
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Affiliation(s)
- Joris Guyon
- INSERM, LAMC, U1029, University Bordeaux, Pessac, France
| | - Candice Chapouly
- INSERM, Biology of Cardiovascular Diseases, U1034, University Bordeaux, Pessac, France
| | - Laetitia Andrique
- INSERM, LAMC, U1029, University Bordeaux, Pessac, France.,VoxCell 3D Plateform, UMS TBMcore 3427, Bordeaux, France
| | | | - Thomas Daubon
- University Bordeaux, CNRS, IBGC, UMR 5095, Bordeaux, France
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42
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3D printing of tissue engineering scaffolds: a focus on vascular regeneration. Biodes Manuf 2021; 4:344-378. [PMID: 33425460 PMCID: PMC7779248 DOI: 10.1007/s42242-020-00109-0] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 10/24/2020] [Indexed: 01/31/2023]
Abstract
Tissue engineering is an emerging means for resolving the problems of tissue repair and organ replacement in regenerative medicine. Insufficient supply of nutrients and oxygen to cells in large-scale tissues has led to the demand to prepare blood vessels. Scaffold-based tissue engineering approaches are effective methods to form new blood vessel tissues. The demand for blood vessels prompts systematic research on fabrication strategies of vascular scaffolds for tissue engineering. Recent advances in 3D printing have facilitated fabrication of vascular scaffolds, contributing to broad prospects for tissue vascularization. This review presents state of the art on modeling methods, print materials and preparation processes for fabrication of vascular scaffolds, and discusses the advantages and application fields of each method. Specially, significance and importance of scaffold-based tissue engineering for vascular regeneration are emphasized. Print materials and preparation processes are discussed in detail. And a focus is placed on preparation processes based on 3D printing technologies and traditional manufacturing technologies including casting, electrospinning, and Lego-like construction. And related studies are exemplified. Transformation of vascular scaffolds to clinical application is discussed. Also, four trends of 3D printing of tissue engineering vascular scaffolds are presented, including machine learning, near-infrared photopolymerization, 4D printing, and combination of self-assembly and 3D printing-based methods.
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43
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Zhang Y, Wang B, Hu J, Yin T, Yue T, Liu N, Liu Y. 3D Composite Bioprinting for Fabrication of Artificial Biological Tissues. Int J Bioprint 2020; 7:299. [PMID: 33585709 PMCID: PMC7875057 DOI: 10.18063/ijb.v7i1.299] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 09/09/2020] [Indexed: 12/13/2022] Open
Abstract
Three-dimensional (3D) bioprinting is an important technology for fabricating artificial tissue. To effectively reconstruct the multiscale structure and multi-material gradient of natural tissues and organs, 3D bioprinting has been increasingly developed into multi-process composite mode. The current 3D composite bioprinting is a combination of two or more printing processes, and oftentimes, physical field regulation that can regulate filaments or cells during or after printing may be involved. Correspondingly, both path planning strategy and process control all become more complex. Hence, the computer-aided design and computer-aided manufacturing (CAD/CAM) system that is traditionally used in 3D printing system is now facing challenges. Thus, the scale information that cannot be modeled in the CAD process should be considered in the design of CAM by adding a process management module in the traditional CAD/CAM system and add more information reflecting component gradient in the path planning strategy.
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Affiliation(s)
- Yi Zhang
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
| | - Bin Wang
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
| | - Junchao Hu
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
| | - Tianyuan Yin
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
| | - Tao Yue
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
| | - Na Liu
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
| | - Yuanyuan Liu
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
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Haykal MM, Nahmias C, Varon C, Martin OCB. Organotypic Modeling of the Tumor Landscape. Front Cell Dev Biol 2020; 8:606039. [PMID: 33330508 PMCID: PMC7732527 DOI: 10.3389/fcell.2020.606039] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 11/03/2020] [Indexed: 12/21/2022] Open
Abstract
Cancer is a complex disease and it is now clear that not only epithelial tumor cells play a role in carcinogenesis. The tumor microenvironment is composed of non-stromal cells, including endothelial cells, adipocytes, immune and nerve cells, and a stromal compartment composed of extracellular matrix, cancer-associated fibroblasts and mesenchymal cells. Tumorigenesis is a dynamic process with constant interactions occurring between the tumor cells and their surroundings. Even though all connections have not yet been discovered, it is now known that crosstalk between actors of the microenvironment drives cancer progression. Taking into account this complexity, it is important to develop relevant models to study carcinogenesis. Conventional 2D culture models fail to represent the entire tumor microenvironment properly and the use of animal models should be decreased with respect to the 3Rs rule. To this aim, in vitro organotypic models have been significantly developed these past few years. These models have different levels of complexity and allow the study of tumor cells alone or in interaction with the microenvironment actors during the multiple stages of carcinogenesis. This review depicts recent insights into organotypic modeling of the tumor and its microenvironment all throughout cancer progression. It offers an overview of the crosstalk between epithelial cancer cells and their microenvironment during the different phases of carcinogenesis, from the early cell autonomous events to the late metastatic stages. The advantages of 3D over classical 2D or in vivo models are presented as well as the most promising organotypic models. A particular focus is made on organotypic models used for studying cancer progression, from the less complex spheroids to the more sophisticated body-on-a-chip. Last but not least, we address the potential benefits of these models in personalized medicine which is undoubtedly a domain paving the path to new hopes in terms of cancer care and cure.
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Affiliation(s)
- Maria M. Haykal
- Université Paris-Saclay, Institut Gustave Roussy, Inserm U981, Biomarqueurs Prédictifs et Nouvelles Stratégies Thérapeutiques en Oncologie, Villejuif, France
| | - Clara Nahmias
- Université Paris-Saclay, Institut Gustave Roussy, Inserm U981, Biomarqueurs Prédictifs et Nouvelles Stratégies Thérapeutiques en Oncologie, Villejuif, France
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Xiao W, Zhang P, Wei H, Yu Y. Rapidly Visible-Light-Mediated Photogelations for One-Step Engineering Multifunctional Tough Hydrogel Tubes. ACS Macro Lett 2020; 9:1681-1686. [PMID: 35617070 DOI: 10.1021/acsmacrolett.0c00621] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Hydrogel tubes as one kind of perfusable tubular materials, show promising applications in a wide spectrum of fields. However, there is still a great challenge to design a rapid, biocompatible, and straightforward strategy for one-step engineering tough hydrogel tubes, which have excellent mechanical properties, unique resilience, and multiple functions. Herein, we explore visible-light-mediated orthogonal photochemistry to achieve the fabrication of tough hydrogel tubes with double networks via a coaxial-nozzle spinning technique under short blue-light irradiation (∼20 s). The as-prepared tubes are tough (2.3 MJ m-3) and have mechanical strength (∼300 kPa) with a critical strain of 16, good fatigue resistance, and resilience (>95% within 3 min). These perfusable tubular hydrogels not only can be knitted and assembled to complicated 2D/3D structures, but also are designed to fabricate functional tubes in one step with the applications in fields of smart materials, soft electronics, and sensors.
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Affiliation(s)
- Wenqing Xiao
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an China, 710000
| | - Ping Zhang
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an China, 710000
| | - Hongqiu Wei
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an China, 710000
| | - You Yu
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an China, 710000
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Brassard-Jollive N, Monnot C, Muller L, Germain S. In vitro 3D Systems to Model Tumor Angiogenesis and Interactions With Stromal Cells. Front Cell Dev Biol 2020; 8:594903. [PMID: 33224956 PMCID: PMC7674638 DOI: 10.3389/fcell.2020.594903] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/05/2020] [Indexed: 12/15/2022] Open
Abstract
In vitro 3D culture systems provide promising tools for screening novel therapies and understanding drug resistance mechanisms in cancer because they are adapted for high throughput analysis. One of the main current challenges is to reproducibly culture patient samples containing cancer and stromal cells to faithfully recapitulate tumor microenvironment and move toward efficient personalized medicine. Tumors are composed of heterogeneous cell populations and characterized by chaotic vascularization in a remodeled microenvironment. Indeed, tumor angiogenesis occurs in a complex stroma containing immune cells and cancer-associated fibroblasts that secrete important amounts of cytokines, growth factors, extracellular vesicles, and extracellular matrix (ECM). This process leads to the formation of inflated, tortuous, and permeable capillaries that display deficient basement membrane (BM) and perivascular coverage. These abnormal capillaries affect responses to anti-cancer therapies such as anti-angiogenic, radio-, and immunotherapies. Current pre-clinical models are limited for investigating interactions between tumor cells and vascularization during tumor progression as well as mechanisms that lead to drug resistance. In vitro approaches developed for vascularization are either the result of engineered cell lining or based on physiological processes including vasculogenesis and sprouting angiogenesis. They allow investigation of paracrine and direct interactions between endothelial and tumor and/or stromal cells, as well as impact of biochemical and biophysical cues of the microenvironment, using either natural matrix components or functionalized synthetic hydrogels. In addition, microfluidic devices provide access to modeling the impact of shear stress and interstitial flow and growth factor gradients. In this review, we will describe the state of the art co-culture models of vascularized micro-tumors in order to study tumor progression and metastatic dissemination including intravasation and/or extravasation processes.
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Affiliation(s)
- Noémie Brassard-Jollive
- Center for Interdisciplinary Research in Biology, College de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France.,Sorbonne Université, Collège Doctoral, Paris, France
| | - Catherine Monnot
- Center for Interdisciplinary Research in Biology, College de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France
| | - Laurent Muller
- Center for Interdisciplinary Research in Biology, College de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France
| | - Stéphane Germain
- Center for Interdisciplinary Research in Biology, College de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France
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Wang B, Liu XM, Liu ZN, Wang Y, Han X, Lian AB, Mu Y, Jin MH, Liu JY. Human hair follicle-derived mesenchymal stem cells: Isolation, expansion, and differentiation. World J Stem Cells 2020; 12:462-470. [PMID: 32742563 PMCID: PMC7360986 DOI: 10.4252/wjsc.v12.i6.462] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/18/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
Hair follicles are easily accessible skin appendages that protect against cold and potential injuries. Hair follicles contain various pools of stem cells, such as epithelial, melanocyte, and mesenchymal stem cells (MSCs) that continuously self-renew, differentiate, regulate hair growth, and maintain skin homeostasis. Recently, MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential. In this review, we describe the applications of human hair follicle-derived MSCs (hHF-MSCs) in tissue engineering and regenerative medicine. We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail. We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages, including supplementation of growth factors, 3D suspension culture technology, and 3D aggregates of MSCs. In addition, we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels, regenerated hair follicles, induced red blood cells, and induced pluripotent stem cells. In summary, the abundance, convenient accessibility, and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.
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Affiliation(s)
- Bo Wang
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Xiao-Mei Liu
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Zi-Nan Liu
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Yuan Wang
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Xing Han
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Ao-Bo Lian
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Ying Mu
- Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Ming-Hua Jin
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Jin-Yu Liu
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
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Acoustic trapping of microbubbles in complex environments and controlled payload release. Proc Natl Acad Sci U S A 2020; 117:15490-15496. [PMID: 32571936 PMCID: PMC7354944 DOI: 10.1073/pnas.2003569117] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Contactless manipulation of microparticles using acoustic waves holds promise for applications ranging from cell sorting to three-dimensional (3D) printing and tissue engineering. However, the unique potential of acoustic trapping to be applied in biomedical settings remains largely untapped. In particular, the main advantage of acoustic trapping over optical trapping, namely the ability of sound to propagate through thick and opaque media, has not yet been exploited in full. Here we demonstrate experimentally the use of the recently developed technique of single-beam acoustical tweezers to trap microbubbles, an important class of biomedically relevant microparticles. We show that the region of vanishing pressure of a propagating vortex beam can confine a microbubble by forcing low-amplitude, nonspherical, shape oscillations, enabling its full 3D positioning. Our interpretation is validated by the absolute calibration of the acoustic trapping force and the direct spatial mapping of isolated bubble echos, for which both find excellent agreement with our theoretical model. Furthermore, we prove the stability of the trap through centimeter-thick layers of bio-mimicking, elastic materials. Finally, we demonstrate the simultaneous trapping of nanoparticle-loaded microbubbles and activation with an independent acoustic field to trigger the release of the nanoparticles. Overall, using exclusively acoustic powering to position and actuate microbubbles paves the way toward controlled delivery of drug payloads in confined, hard-to-reach locations, with potential in vivo applications.
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Recher G, Nassoy P, Badon A. Remote scanning for ultra-large field of view in wide-field microscopy and full-field OCT. BIOMEDICAL OPTICS EXPRESS 2020; 11:2578-2590. [PMID: 32499945 PMCID: PMC7249822 DOI: 10.1364/boe.383329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 04/04/2020] [Accepted: 04/06/2020] [Indexed: 05/14/2023]
Abstract
Imaging specimens over large scales and with a sub-micron resolution is instrumental to biomedical research. Yet, the number of pixels to form such an image usually exceeds the number of pixels provided by conventional cameras. Although most microscopes are equipped with a motorized stage to displace the specimen and acquire the image tile-by-tile, we propose an alternative strategy that does not require to move any part in the sample plane. We propose to add a scanning mechanism in the detection unit of the microscope to collect sequentially different sub-areas of the field of view. Our approach, called remote scanning, is compatible with all camera-based microscopes. We evaluate the performances in both wide-field microscopy and full-field optical coherence tomography and we show that a field of view of 2.2 × 2.2 mm2 with a 1.1 μm resolution can be acquired. We finally demonstrate that the method is especially suited to image motion-sensitive samples and large biological samples such as millimetric engineered tissues.
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Affiliation(s)
- Gaëlle Recher
- LP2N, Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, F-33400 Talence, France
- Institut d'Optique Graduate School & CNRS UMR 5298, F-33400 Talence, France
| | - Pierre Nassoy
- LP2N, Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, F-33400 Talence, France
- Institut d'Optique Graduate School & CNRS UMR 5298, F-33400 Talence, France
| | - Amaury Badon
- LP2N, Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, F-33400 Talence, France
- Institut d'Optique Graduate School & CNRS UMR 5298, F-33400 Talence, France
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50
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Le Maout V, Alessandri K, Gurchenkov B, Bertin H, Nassoy P, Sciumè G. Role of mechanical cues and hypoxia on the growth of tumor cells in strong and weak confinement: A dual in vitro-in silico approach. SCIENCE ADVANCES 2020; 6:eaaz7130. [PMID: 32232163 PMCID: PMC7096162 DOI: 10.1126/sciadv.aaz7130] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 01/03/2020] [Indexed: 06/10/2023]
Abstract
Characterization of tumor growth dynamics is of major importance for cancer understanding. By contrast with phenomenological approaches, mechanistic modeling can facilitate disclosing underlying tumor mechanisms and lead to identification of physical factors affecting proliferation and invasive behavior. Current mathematical models are often formulated at the tissue or organ scale with the scope of a direct clinical usefulness. Consequently, these approaches remain empirical and do not allow gaining insight into the tumor properties at the scale of small cell aggregates. Here, experimental and numerical studies of the dynamics of tumor aggregates are performed to propose a physics-based mathematical model as a general framework to investigate tumor microenvironment. The quantitative data extracted from the cellular capsule technology microfluidic experiments allow a thorough quantitative comparison with in silico experiments. This dual approach demonstrates the relative impact of oxygen and external mechanical forces during the time course of tumor model progression.
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Affiliation(s)
- V. Le Maout
- I2M, Institute of Mechanics and Mechanical Engineering, Univ. Bordeaux, CNRS, ENSAM, Bordeaux INP, Talence, France
| | - K. Alessandri
- LP2N, Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, F-33400 Talence, France
- Institut d’Optique Graduate School and CNRS UMR 5298, F-33400 Talence, France
| | - B. Gurchenkov
- Institut du Cerveau et de la Moëlle épinière (ICM), INSERM U 1127, CNRS UMR 7225, Sorbonne Université, F-75013 Paris, France
| | - H. Bertin
- I2M, Institute of Mechanics and Mechanical Engineering, Univ. Bordeaux, CNRS, ENSAM, Bordeaux INP, Talence, France
| | - P. Nassoy
- LP2N, Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, F-33400 Talence, France
- Institut d’Optique Graduate School and CNRS UMR 5298, F-33400 Talence, France
| | - G. Sciumè
- I2M, Institute of Mechanics and Mechanical Engineering, Univ. Bordeaux, CNRS, ENSAM, Bordeaux INP, Talence, France
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