Cartilage tissue does not promptly elicit an inflammatory response upon injury, hence constraining its capacity for healing and self-regeneration. Mesenchymal Stem Cells (MSC) therapy, enhanced by nanotechnology, offers promising advancements in cartilage repair. Injuries to cartilage often cause chronic pain, where current treatments are inadequate. As MSCs can readily differentiate into chondrocytes and secrete soluble factors, they are essential components in tissue engineering of cartilage repair. Although, like other stem cell applications, clinical applications are restricted by poor post implantation survival and differentiation. Recent studies show that nanoparticles (NPs) can further improve MSC outcomes by promoting cell adhesion, and chondrogenic differentiation allowing for sustained growth factor release. In addition, nanomaterials can improve the biological activity of MSCs, by also facilitating the composition of a conducive microenvironment for cartilage repair. In this review, the application of nanofibrous scaffolds, hydrogels and nanoscale particulate matter to improve mechanical properties in cartilage tissue engineering, are discussed. Moreover, the MSCs and nanotechnology synergistic effects present hope of overcoming the limitations of conventional treatments. Nanotechnology greatly enhances the MSC based cartilage regeneration strategies and could provide better treatment for cartilage related diseases in the future. Future research should be aimed at standardizing MSC harvesting and culturing protocols and contrasting their long-term efficacy.

Aging is a natural process that affects cellular function. In peritoneal dialysis (PD), chronic exposure to dialysate induces oxidative stress (OS) in peritoneal mesothelial cells (PMCs), leading to cellular aging, fibrosis, and reduced dialysis efficacy. Mesenchymal stem cells (MSCs) have shown potential in alleviating cellular aging. This study investigates the role of exosomes (hUMSC-Exos) derived from human umbilical cord MSCs (hUMSCs) in mitigating PMC senescence and explores the underlying mechanisms.

Human peritoneal mesothelial cells (HMrSV5) were cultured with 2.5 % glucose to induce senescence. Aging markers were assessed via Western blotting, β-galactosidase staining, and cell cycle analysis. hUMSC-Exos were characterized using Western blot, electron microscopy, and nanoparticle tracking analysis. Their uptake by HMrSV5 cells was confirmed through fluorescence microscopy. Various concentrations of hUMSC-Exos were tested, and OS levels were evaluated using reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) assays. The impact of the OS inhibitor N-acetyl-L-cysteine (NAC) on aging markers was also examined.

HMrSV5 cells treated with 2.5 % glucose exhibited increased expression of P53, P21, and P16, along with G0/G1 cell cycle arrest. Treatment with 150 μg/mL hUMSC-Exos reduced aging markers, decreased ROS and MDA levels, and increased SOD activity. Similar effects were observed with NAC treatment.

hUMSC-Exos alleviate PMCs aging by inhibiting OS, highlighting their potential to improve PD outcomes.

Tumor cells (TCs) produce exosomes (EXOs), nanovesicles formed in endosomes. Tumor-derived exosomes (TDEs) are tiny, bubble-shaped structures formed by TCs that include microRNAs (miRNA), proteins, enzymes, and copies of DNA and RNA. Many different kinds of cancer rely on TDEs. For instance, TDEs play a large role in the tumor microenvironment (TME) and promote tumor spread via many pathways. Furthermore, TDEs impact the efficacy of cancer treatments. Additionally, because of their low immunogenicity, high biocompatibility, and low toxicity, TDEs have been extensively used as drug delivery vehicles for cancer immunotherapy. Consequently, future cancer treatments may benefit from focusing on both the therapeutic function and the tumorigenic pathways of TDEs. Consequently, in this work, we have examined the roles of TDEs in cancer development, such as tumor angiogenesis, immune system evasion, and tumor metastasis. Then, we reviewed TDEs used to transport anticancer medicines, including chemotherapeutic medications, therapeutic compounds (including miRNA), and anticancer nanoparticles. We have concluded by outlining the challenges of clinical translation, including carcinogenicity and medication resistance, and by offering some suggestions for addressing these issues.

Cardiovascular disease (CVD) remains one of the leading causes of high mortality and morbidity worldwide, posing a substantial threat to global health. Mesenchymal stem cell (MSC) therapy has emerged as a promising treatment approach, primarily through the secretion of various bioactive factors. Exosomes (Exos), in particular, stand out as the most effective components, as their noncoding RNA and proteins play a crucial role in promoting the repair of cardiac function, positioning them a promising cell-free therapy for CVD. However, challenges such as poor stability, low delivery efficiency, weak targeting, and rapid immune-mediated clearance hinder the broader application of Exos, presenting significant obstacles for further clinical translation. Recent advancements in biomaterials, particularly hydrogels, offer new avenues for Exos-based CVD therapies. Hydrogels, with their ability to improve stability, release control, and targeting, have gained considerable attention in the biomedical field. This review explores the latest research developments regarding the treatment of CVD using Exos, and highlights their synergistic application with hydrogels, which provide valuable insights for advancing Exos-based therapies and developing novel therapeutic strategies for CVD.

Cardiovascular diseases are the main cause of death and disability in the clinical setting. Among several pathological conditions, myocardial infarction (MI) is a common clinical finding and happens due to the reduction or complete interruption of blood support. Stem cells and progenitors are valid cell sources with significant potential to alleviate several tissue injuries. Differentiation to mature and functional cells and the release of various growth factors, and cytokines are the main reparative mechanisms by which stem cells mediate their reparative tasks. Exosomes (Exos), a subset of extracellular vesicles (EVs), exhibit great theranostic potential in biomedicine. Along with whole-cell-based therapies, the pre-clinical and clinical application of Exos has been extended in animals and humans with ischemic heart diseases (IHD). Here, in this review article, we aimed to highlight the importance of Exos in IHD and address the mechanism of action by focusing on their regenerative potential.

Exosomes (Exos) are tiny extracellular vesicles containing a variety of active biomolecules that play important parts in intercellular communication and influence the functions of target cells. The potential of Exos in the treatment of dermatological diseases has recently been well appreciated. This review highlights the constituents, function, and delivery of Exos, with a particular focus on their applications in skin therapy. Firstly, we offer a concise overview of the biochemical properties of Exos, including their sources, structures, and internal constituents. Subsequently, the biomedical functions of Exos and the latest advances in the extraction and purification of Exos are summarized. We further discuss the modes of delivery of Exos and underscore the potential of biomaterials in this regard. Finally, we summarize the application of Exo-aided therapy in dermatology. Overall, the objective of this review is to provide a comprehensive perspective on the applications and recent advancements of Exo-based approaches in treating skin diseases, with the intention of guiding future research efforts.

Ferroptosis in the tumor microenvironment (TME) plays a crucial role in the development, metastasis, immune escape, and drug resistance of various types of cancer. A better understanding of ferroptosis in the TME could illuminate novel aspects of this process and promote the development of targeted therapies. Compelling evidence indicates that exosomes are key mediators in regulating the TME. In this respect, it is now understood that exosomes can deliver biologically functional molecules to recipient cells, influencing cancer progression by reprogramming the metabolism of cancer cells and their surrounding stromal cells through ferroptosis. In this review, we focus on the role of exosomes in the TME and describe how they contribute to tumor reprogramming, immunosuppression, and the formation of pre-metastatic niches through ferroptosis. In addition, we highlight exosome-mediated ferroptosis as a potential target for cancer therapy and discuss strategies employing exosomes in ferroptosis treatment. Finally, we outline the current applications and challenges of targeted exosome-mediated ferroptosis therapy in tumor immunotherapy and chemotherapy. Our aim is to advance research on the link between exosomes and ferroptosis in the TME, and we pose questions to guide future studies in this area.

Neurological disorders such as Alzheimer's disease, Parkinson's disease, and stroke pose significant challenges for conventional therapy due to the complexities of the blood-brain barrier (BBB) and the restricted delivery of drugs to the central nervous system. Exosomes, a type of small extracellular vesicle secreted by nearly all cell types, hold substantial promise as delivery vehicles for therapeutic agents in treating these conditions. Notably, stem cell-secreted exosomes have emerged as particularly effective due to their regenerative potential and natural ability to cross the BBB. Similarly, hydrogels have gained recognition as versatile biomaterials capable of supporting sustained release and targeted delivery of therapeutics. The combination of the regenerative properties of stem cell-derived exosomes (SC-Exos) with the structural and functional benefits of hydrogels offers a promising approach for enhancing neurogenesis, modulating neuroinflammation, and facilitating tissue repair. This review explores the origin, structure, and modifications of exosomes as well as the synthesis and incorporation methods of hydrogels in the therapeutic context for debilitating neurological disorders. It highlights recent advancements in using SC-Exos and hydrogels for therapeutic delivery, addressing both current challenges and future applications. Improving our understanding of hydrogels loaded with SC-Exos for cargo transportation and neural tissue regeneration may pave the way for novel therapeutic strategies.

Allergic rhinitis (AR) affects 10-40% of the global population, yet current therapies (drugs, immunotherapy) face limitations in efficacy and safety. Mesenchymal stem cells (MSCs) have emerged as a promising alternative due to their immunomodulatory properties.

Preclinical studies demonstrate that MSCs from adipose, bone marrow, umbilical cord, and tonsils reduce AR symptoms (sneezing, nasal inflammation) and serum IgE (Immunoglobulin E) levels by restoring Th1/Th2 immune equilibrium and enhancing Treg (Regulatory T cells) activity. MSC-derived exosomes and hydrogel-encapsulated formulations further improve targeting and safety. However, clinical translation is hindered by heterogeneous protocols and unresolved long-term risks (e.g., tumorigenicity).

MSC-based therapies offer potential for durable AR remission by addressing immune dysregulation at its root. Future efforts must prioritize standardized production, phase I safety trials, and combination strategies (e.g., exosomes + hydrogels) to accelerate clinical adoption.

Tracheal reconstruction presents a significant global clinical challenge due to the unique structure and function of the trachea, which complicates its repair. Key challenges include restoring tracheal function post-transplantation, managing surgical complications, and ensuring the long-term survival of transplanted tissue. Furthermore, adequate vascularization of the transplanted trachea, along with the repair of cartilage and epithelial cells, is critical for facilitating functional recovery and successful reconstruction. In this study, a decellularized tracheal matrix was extracted to preserve its natural bioactivity. Nanoclay and GelMA were then employed as carrier materials to integrate with the decellularized tracheal matrix, forming a hydrogel scaffold. Both nanoclay and GelMA offer tunable porous structures and surface properties that promote cell adhesion and proliferation, while providing sufficient mechanical support. By leveraging the biological functions of endothelial progenitor cell-derived exosomes, we successfully loaded exosomes onto the decellularized extracellular matrix, creating a novel cell-free tracheal scaffold for investigating tracheal defect repair. The scaffold exhibited excellent biocompatibility, promoting graft vascularization and facilitating the repair of tracheal cartilage and epithelium. These findings hold significant promise for advancing tracheal reconstruction surgery and offer valuable insights for future research in this area.

Damage to nerves negatively impacts quality of life and causes considerable morbidity. Self-regeneration is a special characteristic of the nervous system, yet how successful regeneration is accomplished remains unclear. Research on nerve regeneration is advancing and accelerating successful nerve recovery with potential new approaches. Eukaryote cells release extracellular vesicles (EVs), which control intercellular communication in both health and disease. More and more, EVs such as microvesicles and exosomes (EXOs) are being recognized as viable options for cell-free therapies that address complex tissue regeneration. The present study highlights the functional relevance of EVs in regenerative medicine for nerve-related regeneration. A subclass of EVs, EXOs were first identified as a way for cells to expel undesirable cell products. These nanovesicles have a diameter of 30-150 nm and are secreted by a variety of cells in conditions of both health and illness. Their benefits include the ability to promote endothelial cell growth, inhibit inflammation, encourage cell proliferation, and regulate cell differentiation. They are also known to transport functional proteins, metabolites, and nucleic acids to recipient cells, thus playing a significant role in cellular communication. EXOs impact an extensive array of physiological functions, including immunological responses, tissue regeneration, stem cell conservation, communication within the central nervous system, and pathological processes involving cardiovascular disorders, neurodegeneration, cancer, and inflammation. Their biocompatibility and bi-layered lipid structure (which shields the genetic consignment from deterioration and reduces immunogenicity) make them appealing as therapeutic vectors. They can pass through the blood brain barrier and other major biological membranes because of their small size and membrane composition. The creation of modified EXOs is a dynamic area of research that supports the evaluation of diverse therapeutic freights, improvement of target selectivity, and manufacturing optimization.

The treatment of congenital deformities, traumatic injuries, infectious diseases, and tumors in the craniomaxillofacial (CMF) region is complex due to the intricate nature of the tissues involved. Conventional treatments such as bone grafts and cell transplantation face limitations, including the need for multiple surgeries, complications, and safety concerns.

This paper aims to provide a comprehensive analysis of the role of exosomes (EXOs) in CMF and dental tissue regeneration and to explore their potential applications in regenerative dental medicine.

An extensive review of advancements in tissue engineering, materials sciences, and nanotechnology was conducted to evaluate the development of delivery systems for EXOs-based therapies. The analysis included how EXOs, as nanovesicles released by cells, can be modified to target specific cells or loaded with functional molecules for drug or gene delivery.

EXOs have emerged as a promising alternative to cell transplant therapy, offering a safer method for cell communication and epigenetic control. EXOs transport important proteins and genetic materials, facilitating intercellular communication and delivering therapeutics effectively. The potential of EXOs in personalized medicine, particularly in diagnosing, customizing treatment, and predicting patient responses, is highlighted.

EXO-mediated therapy holds significant potential for advancing tissue regeneration, offering targeted, personalized treatment options with reduced side effects. However, challenges in purification, production, and standardized protocols need to be addressed before its clinical application can be fully realized.

In this article, we revisit an article, which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells (MSCs) for targeted delivery of gemcitabine in pancreatic cancer treatment. The experimental results demonstrated that the exosome-based drug delivery system derived from MSCs significantly augmented apoptosis in pancreatic cancer cells. The biocompatibility, targeting specificity, and low immunogenicity of exosomes render them as optimal carriers for drug delivery, enabling precise administration of therapeutics to diseased tissues while mitigating adverse effects, thereby achieving targeted treatment of cancer cells and significantly enhancing anti-tumor efficacy. However, the clinical application of exosome drug delivery platforms in oncology still presents challenges, necessitating further optimization to ensure their stability and efficacy. This study focuses on elucidating the advantages of exosomes as a drug delivery platform, exploring the utilization of MSC-derived exosomes in oncology therapy, and discussing their potential and future directions in cancer treatment.

Exosomes, nanosized extracellular vesicles released by various cell types, are intensively studied for the diagnosis and treatment of cancer and neurodegenerative diseases, and they also display high usability in regenerative medicine. Emphasizing their diagnostic potential, exosomes serve as carriers of disease-specific biomarkers, enabling non-invasive early detection and personalized medicine. The cargo loading of exosomes with therapeutic agents presents an innovative strategy for targeted drug delivery, minimizing off-target effects and optimizing therapeutic interventions. In regenerative medicine, exosomes play a crucial role in intercellular communication, facilitating tissue regeneration through the transmission of bioactive molecules. While acknowledging existing challenges in standardization and scalability, ongoing research efforts aim to refine methodologies and address regulatory considerations. In summary, this review underscores the transformative potential of exosomes in reshaping the landscape of medical interventions, with a particular emphasis on cancer, neurodegenerative diseases, and regenerative medicine.

Three-dimensional bioprinting is a new advance in tissue engineering and regenerative medicine. Bioprinting allows manufacturing three-dimensional (3D) structures that mimic tissues or organs. The bioinks used are mainly made of natural or synthetic polymers that must be biocompatible, printable, and biodegradable. These bioinks may incorporate progenitor cells, favoring graft implantation and regeneration of injured tissues. However, the natures of biomaterials, bioprinting processes, a lack of vascularization, and immune responses are factors that limit the viability and functionality of implanted cells and the regeneration of damaged tissues. These limitations can be addressed by incorporating extracellular vesicles (EV) into bioinks. Indeed, EV from progenitor cells may have regenerative capacities, being similar to those of their source cells. Therefore, their combinations with biomaterials can be used in cell-free therapies. Likewise, they can complement the manufacture of bioinks by increasing the viability, differentiation, and regenerative ability of incorporated cells. Thus, the main objective of this review is to show how the use of 3D bioprinting technology can be used for the application of EV in regenerative medicine by incorporating these nanovesicles into hydrogels used as bioinks. To this end, the latest advances derived from in vitro and in vivo studies have been described. Together, these studies show the high therapeutic potential of this strategy in regenerative medicine.

Mesenchymal stem/stromal cells (MSCs) are a valuable source of paracrine factors, as they have a remarkable secretory capacity, and there is a sizeable knowledge base to develop industrial and clinical production protocols. Promising cell-free approaches for tissue regeneration and immunomodulation are driving research towards secretome applications, among which extracellular vesicles (EVs) are steadily gaining attention. However, the manufacturing and application of EVs is limited by insufficient yields, knowledge gaps, and low standardization. Facing these limitations, hydrogels represent a versatile three-dimensional (3D) culture platform that can incorporate extracellular matrix (ECM) components to mimic the natural stem cell environment in vitro; via these niche-mimicking properties, hydrogels can regulate MSCs' morphology, adhesion, proliferation, differentiation and secretion capacities. However, the impact of the hydrogel's architectural, biochemical and biomechanical properties on the production of EVs remains poorly understood, as the field is still in its infancy and the interdependency of culture parameters compromises the comparability of the studies. Therefore, this review summarizes and discusses the reported effects of hydrogel encapsulation and culture on the secretion of MSC-EVs. Considering the effects of cell-material interactions on the overall paracrine activity of MSCs, we identify persistent challenges from low standardization and process control, and outline future paths of research, such as the synergic use of hydrogels and bioreactors to enhance MSC-EV generation.

Exosomes are small vesicles with diameters ranging from 30 to 150 nm. They originate from cellular endocytic systems. These vesicles contain a rich payload of biomolecules, including proteins, nucleic acids, lipids, and metabolic products. Exosomes mediate intercellular communication and are key regulators of a diverse array of biological processes, such as oxidative stress and chronic inflammation. Furthermore, exosomes have been implicated in the pathogenesis of infectious diseases, autoimmune disorders, and cancer. Aging is closely associated with the onset and progression of numerous diseases and is significantly influenced by exosomes. Recent studies have consistently highlighted the important functions of exosomes in the regulation of cellular senescence. Additionally, research has explored their potential to delay aging, such as the alleviatory effects of stem cell-derived exosomes on the aging process, which offers broad potential for the development and application of exosomes as anti-aging therapeutic strategies. This review aims to comprehensively investigate the multifaceted impact of exosomes while concurrently evaluating their potential applications and underscoring their strategic significance in advancing anti-aging strategies.

Exosomes have emerged as promising therapeutic agents in regenerative medicine. This review introduces a novel cell type-oriented perspective to systematically analyze exosomal properties in regenerative therapies. To our knowledge, this review is the first to comprehensively compare exosomes based on cellular source type, offering unprecedented insights into selecting optimal exosome producers for targeted regenerative applications. Factors beyond cellular origin influencing exosomal therapeutic efficacy, such as donor sites and collection methods, are also explored here. By synthesizing key advances, we propose promising research directions in the end. We aim to accelerate the development of more effective exosome-based regenerative therapies and highlight underexplored directions in this rapidly evolving field.

Spinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims to develop a novel composite material combining enzymatic nanoparticles and nerve growth factor (NGF) to modulate the immune microenvironment and enhance SCI repair.

CeMn nanoparticles (NP) and CeMn NP-polyethylene glycol (PEG) nanozymes were synthesized via sol-gel reaction and DSPE-mPEG modification. Transmission Electron Microscopy, Selected-Area Electron Diffraction, X-ray Diffraction and X-ray Photoelectron Spectroscopy confirmed their crystalline structure, mixed-valence states, and redox properties. Size uniformity, biocompatibility, and catalytic activity were assessed via hydrodynamic diameter, zeta potential, and elemental analysis. The Lightgel/NGF/CeMn NP-PEG composite was synthesized and characterized via electron microscopy, compression testing, rheological analysis, NGF release kinetics, and 30-day degradation studies. Both in vitro and in vivo experiments were conducted to evaluate the therapeutic effects of the composite on SCI.

The Lightgel/NGF/CeMn NP-PEG composite was successfully synthesized, exhibiting favorable physical properties. At a CeMn NP-PEG concentration of 4 µg/mL, the composite maintained cell viability and demonstrated enhanced biological activity. It also showed superior mechanical properties and an effective NGF release profile. Notably, the composite significantly upregulated the expression of nerve growth-associated proteins, reduced inflammatory cytokines, scavenged reactive oxygen species (ROS), and promoted M2 macrophage polarization by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. In a rat SCI model, it facilitated functional recovery and attenuated inflammation.

The Lightgel/NGF/CeMn NP-PEG composite shows significant therapeutic promise for SCI, effectively eliminating ROS, promoting M2 macrophage polarization, reducing pro-inflammatory cytokines, and supporting neuronal regeneration. These effects substantially enhance motor function in SCI rats, positioning it as a promising candidate for future clinical applications.

Extracellular vesicles (EVs) are membrane-bound vesicles that are shed or secreted from the cell membrane and enveloped by a lipid bilayer. They possess stability, low immunogenicity, and non-cytotoxicity, exhibiting extensive prospects in regenerative medicine (RM). However, natural EVs pose challenges, such as insufficient targeting capabilities, potential biosafety concerns, and limited acquisition pathways. Although engineered EVs demonstrate excellent therapeutic efficacy, challenges such as low production yield and the complexity of engineering modifications constrain their further clinical applications. Bacteria have advantages such as rapid proliferation, diverse gene editing methods, mature cultivation techniques, and relatively easy preparation of bacterial EVs (BEVs), which can be used to effectively address the challenges currently encountered in the field of EVs. This review provides a description of the biogenesis and pathophysiological functions of BEVs, and strategies for optimizing BEVs preparation to attain efficiency and safety are discussed. An analysis of natural characteristics of BEVs is also conducted to explore how to leverage their advantages or mitigate their limitations, thereby overcoming constraints on the application of BEVs in RM. In summary, engineered BEVs possess characteristics such as high production yield, excellent stability, and high drug-delivering capabilities, laying the foundation for their application in RM.

Previous cesarean scar defect (PCSD), also acknowledged as the myometrium of uterus defects, which commonly results in myometrial discontinuity between the uterine and cervical cavity. Current literatures have indicated the efficacy of MSCs and MSC-derived exosomes (MSC-Exos) for diverse refractory disease administration, yet the feasibility of MSC-Exos for PCSD treatment is largely obscure. In this study, we took advantage of the in vivo myofibrotic model for mimicking the typical manifestation of PCSD and the assessment of fertility. Meanwhile, the ex vivo scratch wound healing model is used for exploring the underlying molecular mechanism. On the one hand, we took advantage of the TGF-β-induced in vitro myofibrotic model and the full-thickness uterine injury rat model to verify the efficacy of human umbilical cord MSC-derived exosomes (hUC-MSC-Exos). On the other hand, with the aid of CHK1 overexpression and β-TrCP knockdown, together with multifaceted biological analyses (e.g., histopathological sections, qRT-PCR assay, western-blotting analysis, Co-IP assay, protein degradation and ubiquitination), we further dissected the underlying regulatory mechanism. We identified hUC-MSC-Exos and verified the suppressive effect of hUC-MSC-Exos upon TGF-β-induced in vitro myofibrotic model and full-thickness uterine injury in rats via delivering β-TrCP. Furthermore, we found that β-TrCP in hUC-MSC-Exos facilitated the ubiquitination degradation of CHK1 and inhibited the myofibrosis. Collectively, our data indicated the preferable ameliorative effect of hUC-MSC-Exos upon both the in vitro and in vivo myofibrotic models, together with the β-TrCP and CHK1-mediated regulatory mechanism. Our findings provided new references of hUC-MSC-Exos-based regimens for PCSD management in future.

Chronic wounds present a major healthcare challenge around the world, and significant hurdles remain in their effective treatment due to limitations in accessible treatment options. Mesenchymal stem cells (MSCs) with multifunctional differentiation and modulatory properties have been delivered to chronic wounds to enhance closure but have limited engraftment when delivered without a scaffold. In this study, hybrid porous hydrogel foams composed of modified polyvinyl alcohol and gelatin were developed that are suitable for rapid and facile MSC encapsulation, fully degradable, and supportive of wound healing. Rapid fabrication and encapsulation within porous foams was achieved using a cytocompatible gas blowing process. The hybrid hydrogels have tunable degradation rates based on chemistry, with complete mass loss achieved within 2-6 weeks, which is compatible with chronic wound closure rates. High encapsulated A375 epithelial cell and MSC viability with maintained cell functionality over 2 weeks reveals the potential of these hydrogels to serve as cell delivery systems for chronic wound treatment. An ex vivo porcine skin wound model demonstrated enhanced healing after application of cell-laden hydrogel foams. Overall, hybrid hydrogel foams with encapsulated therapeutic cells have the capacity for robust wound healing and are a promising platform for chronic wound dressings.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal death and neurological dysfunction for which no particularly effective treatment is available. Stem cells possess multi-directional differentiation potential and can secrete a variety of cytokines. They not only have the ability to replace tissue and repair lesions but also improve neurological damage caused by HIBD through paracrine mechanisms, including anti-apoptosis, reduction of inflammation, and promotion of endogenous repair. Recently, as research on stem cells, particularly mesenchymal stem cells, has deepened, the application of stem cells in treating HIBD has become a prominent research topic, yielding fruitful results, particularly regarding the neuroprotective effects and mechanisms of the stem cell paracrine pathway. With advances in stem cell injection, distribution, and biomaterial incorporation, applications of stem cells have become more widespread and comprehensive. This review summarizes and discusses the research progress on stem cells in HIBD treatment to provide theoretical support for HIBD treatment and enhance the feasibility of clinical translation.

Despite that the clinical application of titanium-based implants has achieved great success, patients' own diseases and/or unhealthy lifestyle habits often lead to implant failure. Many studies have been carried out to modify titanium implants to promote osseointegration and implant success. Recent studies showed that exosomes, proactively secreted extracellular vesicles by mammalian cells, could selectively target and modulate the functions of recipient cells such as macrophages, nerve cells, endothelial cells, and bone marrow mesenchymal stem cells that are closely involved in implant osseointegration. Accordingly, using exosomes to functionalize titanium implants has been deemed as a novel and effective way to improve their osseointegration ability. Herein, recent advances pertaining to surface functionalization of titanium implants with exosomes are analyzed and discussed, with focus on the role of exosomes in regulating the functions of osseointegration-related cells, and their immobilization strategies as well as resultant impact on osseointegration ability.

Schizophrenia is a complex psychiatric disorder, and genetic and environmental factors have been implicated in its development. Dysregulated glutamatergic and dopaminergic transmission pathways are involved in schizophrenia development. Besides genetic mutations, epigenetic dysregulation has a considerable role in dysregulating molecular pathways involved in schizophrenia. MicroRNAs (miRNAs) are small, non-coding RNAs that target specific mRNAs and inhibit their translation into proteins. As epigenetic factors, miRNAs regulate many genes involved in glutamate and dopamine signaling pathways; thereby, their dysregulation can contribute to the development of schizophrenia. Secretion of specific miRNAs from damaged cells into body fluids can make them one of the ideal non-invasive biomarkers in the early diagnosis of schizophrenia. Also, understanding the molecular mechanisms of miRNAs in schizophrenia pathogenesis can pave the way for developing novel treatments for patients with schizophrenia. In this study, we reviewed the glutamatergic and dopaminergic pathophysiology and highlighted the role of miRNA dysregulation in schizophrenia development. Besides, we shed light on the significance of circulating miRNAs for schizophrenia diagnosis and the recent findings on the miRNA-based treatment for schizophrenia.

Wound management is a major global health problem. With the rising incidence of diabetic wounds, accidents, and other injuries, the demand for prompt wound treatment has become increasingly critical. Millions of people suffer from serious, large wounds resulting from major accidents, surgeries, and wars. These wounds require considerable time to heal and are susceptible to infection. Furthermore, chronic wounds, particularly in elderly and diabetic patients, often require frequent medical interventions to prevent complications. Consequently, wound management imposes a significant economic burden worldwide. The complications arising from wound infections can vary from localized issues to systemic effects. The most severe local complication of wound infection is the non-healing, which results from the disruption of the wound-healing process. This often leads to significant pain, discomfort, and psychological trauma for the patient. Systemic complications may include cellulitis, osteomyelitis, and septicemia. Mesenchymal stem cells are characterized by their high capacity for division, making them suitable candidates for the treatment of tissue damage. Additionally, they produce antimicrobial peptides and various cytokines, which enhance their antimicrobial activity. Evidence shows that phages are effective in treating wound-related infections, and phage therapy has proven to be highly effective for patients when administered correctly. The purpose of this article is to explore the use of bacteriophages and mesenchymal stem cells in wound healing and infection management.

The endometrium is essential to the development of embryos and pregnancy. Human umbilical cord mesenchymal stem cells (HUCMSCs) are promising stem cell sources. HUCMSCs self-renew quickly and are painless to collect. Spermidine is an inherent polyamine needed for cellular and molecular processes that regulate physiology and function. HUCMSCs and spermidine (SN) may heal intrauterine adhesions. HUCMSCs were investigated for endometrial repair in rats. Composite hydrogels are used for medical exosome implantation, including their materials, properties, and embedding procedures. This study examined whether bioengineered hydrogel-loaded exosomes from HUCMSCs and spermidine prenatally improved conception rates in mice with poor endometrial lining. The data show that HUCMSC and SN provide a good experimental base for HUCMSC safety and intrauterine treatment in rats. Western blots, exosome structural analysis, pregnancy outcomes, flow cytometry, H&E staining, immunohistochemistry, and immunofluorescence labelling found and recovered the aberrant area. HUCM-derived stem cells and spermidine-derived exosomes biophysically match. These traits strengthen and prolong endometrial function. Pregnant rats with HUCMSC and SN had thinner endometrium. Hydrogel-incorporated HEHUCMSC and SN exosomes may improve IUI in rats with thin endometrium.

The most prevalent and harmful injuries are burns, which are still a major global health problem. Burn injuries can cause issues because they boost the inflammatory and metabolic response, which can cause organ malfunction and systemic failure. On the other hand, a burn wound infection creates an environment that is conducive to the growth of bacteria and might put the patient at risk for sepsis. In addition, scarring is unavoidable, and this results in patients having functional and cosmetic issues. Wound healing is an amazing phenomenon with a complex mechanism that deals with different types of cells and biomolecules. Cell therapy using stem cells is one of the most challenging treatment methods that accelerates the healing of burn wounds. Since 2000, the use of mesenchymal stem cells (MSCs) in regenerative medicine and wound healing has increased. They can be extracted from various tissues, such as bone marrow, fat, the umbilical cord, and the amniotic membrane. According to studies, stem cell therapy for burn wounds increases angiogenesis, has anti-inflammatory properties, slows the progression of fibrosis, and has an excellent ability to differentiate and regenerate damaged tissue. Figuring out the main preclinical and clinical problems that stop people from using MSCs and then suggesting the right ways to improve therapy could help show the benefits of MSCs and move stem cell-based therapy forward. This review's objective was to assess mesenchymal stem cell therapy's contribution to the promotion of burn wound healing.

Conditioned media (CM) is derived from mesenchymal stem cells (MSC) culture and contains biologically active components. CM is easy to handle and reduces inflammation while repairing injured joints. Combination therapy of the CM with cross-linked hyaluronic acid (HA) could ameliorate the beneficial effect of HA in treating degenerative changes of articulating surfaces associated with arthritic rats' temporomandibular joints (TMJs). This study aimed to evaluate the therapeutic potential of HA hydrogel combined with bone marrow stem cells-conditioned medium (BMSCs-CM) on the articulating surfaces of TMJs associated with complete Freund's adjuvant (CFA)-induced arthritis. Fifty female Sprague-Dawley rats were divided randomly into five equal groups. Rats of group I served as the negative controls and received intra-articular (IA) injections of 50 µl saline solution, whereas rats of group II were subjected to twice IA injections of 50 µg CFA in 50 µl; on day 1 of the experiment to induce persistent inflammation and on day 14 to induce arthritis. Rats of group III and IV were handled as group II and instead, they received an IA injection of 50 µl HA hydrogel and 50 µl of BMSCs-CM, respectively. Rats of group V were given combined IA injections of 50 µl HA hydrogel and BMSCs-CM. All rats were euthanized after the 4th week of inducing arthritis. The joints were processed for sectioning and histological staining using hematoxylin and eosin, Masson's trichrome and toluidine blue special staining, and immunohistochemical staining for nuclear factor-kappa B (NF-κB). SPSS software was used to analyze the data and one-way analysis of variance followed by post-hoc Tukey statistical tests were used to test the statistical significance at 0.05 for alpha and 0.2 for beta. In the pooled BMSC-CM, 197.14 pg/ml of platelet-derived growth factor and 112.22 pg/ml of interleukin-10 were detected. Compared to TMJs of groups III and IV, TMJs of group V showed significant improvements (P = 0.001) in all parameters tested as the disc thickness was decreased (331.79 ± 0.73), the fibrocartilaginous layer was broadened (0.96 ± 0.04), and the amount of the trabecular bone was distinctive (19.35 ± 1.07). The mean values for the collagen amount were increased (12.29 ± 1.38) whereas the mean values for the NF-κB expression were decreased (0.62 ± 0.15). Combination therapy of HA hydrogel and BMSCs-CM is better than using HA hydrogel or BMSCs-CM, separately to repair degenerative changes in rats' TMJs associated with CFA-induced arthritis.

Sjögren's syndrome (SS) is a chronic autoimmune disease caused by immune system disorders. The main clinical manifestations of SS are dry mouth and eyes caused by the destruction of exocrine glands, such as the salivary and lacrimal glands, and systemic manifestations, such as interstitial pneumonia, interstitial nephritis and vasculitis. The pathogenesis of this condition is complex. However, this has not been fully elucidated. Treatment mainly consists of glucocorticoids, disease-modifying antirheumatic drugs and biological agents, which can only control inflammation but not repair the tissue. Therefore, identifying methods to regulate immune disorders and repair damaged tissues is imperative. Cell therapy involves the transplantation of autologous or allogeneic normal or bioengineered cells into the body of a patient to replace damaged cells or achieve a stronger immunomodulatory capacity to cure diseases, mainly including stem cell therapy and immune cell therapy. Cell therapy can reduce inflammation, relieve symptoms and promote tissue repair and regeneration of exocrine glands such as the salivary glands. It has broad application prospects and may become a new treatment strategy for patients with SS. However, there are various challenges in cell preparation, culture, storage and transportation. This article reviews the research status and prospects of cell therapies for SS.

Mesenchymal stem cells (MSCs) hold immense therapeutic potential due to their regenerative and immunomodulatory properties. However, to utilize this potential, it is crucial to optimize their in vitro cultivation conditions. Three-dimensional (3D) culture methods using cell-laden hydrogels aim to mimic the physiological microenvironment in vitro, thus preserving MSC biological functionalities. Cellulosic hydrogels are particularly promising due to their biocompatibility, sustainability, and tunability in terms of chemical, morphological, and mechanical properties. This study investigated the impact of (1) two physical crosslinking scenarios for hydrogels derived from anionic cellulose nanofibers (to-CNF) used to encapsulate adipose-derived MSCs (adMSCs) and (2) physiological culture conditions on the in vitro proliferation, differentiation, and extracellular vesicle (EV) production of these adMSCs. The results revealed that additional Ca2+-mediated crosslinking, intended to complement the self-assembly and gelation of aqueous to-CNF in the adMSC cultivation medium, adversely affected both the mechanical properties of the hydrogel spheres and the growth of the encapsulated cells. However, cultivation under dynamic and hypoxic conditions significantly improved the proliferation and differentiation of the encapsulated adMSCs. Furthermore, it was demonstrated that the adMSCs in the CNF hydrogel spheres exhibited potential for scalable EV production with potent immunosuppressive capacities in a bioreactor system. These findings underscore the importance of physiological culture conditions and the suitability of cellulosic materials for enhancing the therapeutic potential of MSCs. Overall, this study provides valuable insights for optimizing the in vitro cultivation of MSCs for various applications, including tissue engineering, drug testing, and EV-based therapies.

Stem cell-based therapies hold significant promise for chronic wound healing and skin appendages regeneration, but challenges such as limited stem cell lifespan and poor biocompatibility of delivery systems hinder clinical application. In this study, an in situ delivery system for human adipose-derived stem cells is developed (hADSCs) to enhance diabetic wound healing. The system utilizes a photo-crosslinking recombinant human type III collagen (rHCIII) hydrogel to encapsulate hADSCs, termed the hADSCs@rHCIII hydrogel. This hydrogel undergoes local crosslinking at the wound site, establishing a sturdy 3D niche suitable for stem cell function. Consequently, the encapsulated hADSCs exhibit strong attachment and spreading within the hydrogels, maintaining their proliferation, metabolic activity, and viability for up to three weeks in vitro. Importantly, in vivo studies demonstrate that the hADSCs@rHCIII hydrogel achieves significant in situ delivery of stem cells, prolonging their retention within the wound. This ultimately enhances their immunomodulatory capabilities, promotes neovascularization and granulation tissue formation, facilitates matrix remodeling, and accelerates healing in a diabetic mouse wound model. Collectively, these findings highlight the potential of the conveniently-prepared and user-friendly hADSCs@rHCIII hydrogel as a promising therapeutic approach for diabetic wound treatment and in situ skin regeneration.

Treating cartilage damage is challenging as its ability for self-regeneration is limited. Left untreated, it can progress to osteoarthritis (OA), a joint disorder characterized by the deterioration of articular cartilage and other joint tissues. Surgical options, such as microfracture and cell/tissue transplantation, have shown promise as techniques to harness the body's endogenous regenerative capabilities to promote cartilage repair. Nonetheless, these techniques have been scrutinized due to reported inconsistencies in long-term outcomes and the tendency for the defects to regenerate as fibrocartilage instead of the smooth hyaline cartilage native to joint surfaces. Orthobiologics are medical therapies that utilize biologically derived substances to augment musculoskeletal healing. These treatments are rising in popularity because of their potential to enhance surgical standards of care. More recent developments in orthobiologics have focused on the role of exosomes in articular cartilage repair. Exosomes are nano-sized extracellular vesicles containing cargo such as proteins, lipids, and nucleic acids, and are known to facilitate intercellular communication, though their regenerative potential still needs to be fully understood. This review aims to demonstrate the advancements in cartilage regeneration, highlight surgical and biological treatment options, and discuss the recent strides in understanding the precise mechanisms of action involved.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Tissue engineering and regenerative medicine (TERM) is an emerging field that has provided new therapeutic opportunities by delivering innovative solutions. The development of nontraditional therapies for previously unsolvable diseases and conditions has brought hope and excitement to countless individuals globally. Many regenerative medicine therapies have been developed and delivered to patients clinically. The technology platforms developed in regenerative medicine have been expanded to various medical areas; however, their applications in colorectal surgery remain limited. Applying TERM technologies to engineer biological tissue and organ substitutes may address the current therapeutic challenges and overcome some complications in colorectal surgery, such as inflammatory bowel diseases, short bowel syndrome, and diseases of motility and neuromuscular function. This review provides a comprehensive overview of TERM applications in colorectal surgery, highlighting the current state of the art, including preclinical and clinical studies, current challenges, and future perspectives. This article synthesizes the latest findings, providing a valuable resource for clinicians and researchers aiming to integrate TERM into colorectal surgical practice.

3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction.

In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography. The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes' effect of promotion vaginal reconstruction and to explore the mechanism in this process.

It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway.

The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents as benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, and minimal immunogenicity, positioning them as a therapeutic innovation for liver diseases. Therefore, this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics, and support the development of MSC-based therapy in the treatment of NAFLD.

It is common for maladies and trauma to cause significant bone deterioration in the craniofacial bone, which can cause patients to experience complications with their appearance and their ability to function. Regarding grafting procedures' complications and disadvantages, the newly emerging field of tissue regeneration has shown promise. Tissue -engineered technologies and their applications in the craniofacial region are increasingly gaining prominence with limited postoperative risk and cost. MSCs-derived exosomes are widely applied in bone tissue engineering to provide cell-free therapies since they not only do not cause immunological rejection in the same way that cells do, but they can also perform a cell-like role. Additionally, the hydrogel system is a family of multipurpose platforms made of cross-linked polymers with considerable water content, outstanding biocompatibility, and tunable physiochemical properties for the efficient delivery of commodities. Therefore, the promising exosome-loaded hydrogels can be designed for craniofacial bone regeneration. This review lists the packaging techniques for exosomes and hydrogel and discusses the development of a biocompatible hydrogel system and its potential for exosome continuous delivery for craniofacial bone healing.