Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface

Table 1 Biofunctionlization of orthopaedic implant with bioactive ceramic to regulate bone marrow mesenchymal stem cell behavior

Method	Preparation of bioactive ceramic	Cell response	Ref.
Plasma spraying	TiO2-HA nanocomposite powders were thermally sprayed via the HVOF (high-velocity oxy-fuel) technique.	HBMSCs have stronger initial adhesion and favor osteogenic differentiation.	Dimitrievska et al[26]
	Ta-incorporated HA coatings were fabricated using the plasma spray technique on a titanium substrate.	Ta-incorporated HA coating could promote initial adhesion, faster proliferation, and osteogenic differentiation of BMSCs.	Lu et al[28]
	An atmosphere plasma spray system was applied to spray the synthesized 40-80 μm powders onto the treated substrates.	The attachment and proliferation of BMSCs were more significantly on akermanite coatings than on HA coatings.	Yi et al[31]
Sol-gel method	Ti disks were etched with the mixed solution of HF and H2SO4. Next, EtOH solutions containing tetrabutyl titanate (TBT) were spin-coated onto samples.	The micro/nano-level structure of large particles (80 nm) significantly promoted MSC proliferation and differentiation.	Shen et al[23]
	Pre-hydrolyzed silica solution was added to a solution containing the pores structure-directing agents dissolved in ethanol.	The silica coatings accelerate the adhesive response of early BMSCs and promote BMSC osteogenic differentiation.	Inzunza et al[34]

HVOF: High-velocity oxy-fuel; HBMSCs: Human bone marrow-derived mesenchymal stem cells; HA: Hydroxyapatite; BMSCs: Bone marrow-derived mesenchymal stem cells; HF: Hydrofluoric acid; H₂SO₄: Sulfuric acid; TBT: Tetrabutyl titanate; MSC: Mesenchymal stem cell.

Table 2 Surface topography to regulate bone marrow mesenchymal stem cell behavior

Method	Treatment process	Cell response	Ref.
Chemical treatments	Commercial pure Ti was immersed into KOH solutions.	The differentiation levels of ALP and OCN were significantly increased.	Cai et al[38]
	The Ti disks were immersed into solutions of polyphosphoric acid.	Significantly higher cell attachment and proliferation were also found on Ti treated with polyphosphoric acid.	Maekawa et al[40]
	Surfaces submitted to polishing plus etching with 0.8% HF, 13% HNO3 solution.	Rough surfaces submitted to acid-etching favor undifferentiated BMSCs into osteogenic lineage cells.	Silva et al[42]
	The Ti disks were pickled in oxalic acid solution and NaOH, respectively.	Although BMSC adhesion and osteogenesis were promoted, proliferation was significantly inhibited on treated surfaces.	Li et al[47]
	The titanium was treated with H2O2.	H2O2-treated surfaces were beneficial for promoting BMSC attachment, proliferation, and osteogenic differentiation.	Daw et al[52]
	The anodic oxidation was carried out to prepare nanotube on titanium surface.	NT30 supported adhesion, stretching, proliferation, and osteogenic differentiation of BMSCs.	Xu et al[24]
Electrochemical anodization	Nanonets on titanium surfaces were prepared.	BMSC cultured on nanonets structured Ti surfaces present a high frequency of alignment.	Grimalt et al[53]
	The Ti disks were micro-arc oxidized in an electrolyte solution.	The MAO-coating significantly promoted adhesion and osteogenic differentiation of BMSCs by mediating the integrin β1 signaling pathway.	Li et al[57]
	O-PIII treatment was performed in a high-vacuum chamber with a radio frequency plasma source.	O-PIII treatment could enhance the adhesion of BMSCs.	Yang et al[59]
Plasma ion implantation and deposition	O-PIII treatment was performed in a high-vacuum chamber with a radio frequency plasma source.	The group treated with the highest concentration of oxygen ions has the best effect on adhesion, migration, proliferation, and differentiation of BMSCs.	Yang et al[60]
	The Ti-based alloy was modified by electropolishing and plasma electrolytic oxidation process.	The calcium-ion-implanted titanium remarkably improved BMSC adhesion and proliferation compared to the untreated sample.	Michalska et al[61]
	Highly ionized Ca and Mg plasmas were generated from a filtered vacuum arc source and accelerated within the electric field between a sheath and the substrates.	Initial cell attachment on a titanium surface can be improved by Ca and Mg ion implantation. In addition, the expression of osteogenic-related genes like RUNX2 and type I collagen was higher in the Mg ion-implanted surface.	Won et al[62]
	The Ti discs were polished with abrasive grit (grades 240–600), and then treated with laser radiation at various fluences (132, 210, or 235 J/cm2).	Laser-modified titanium surfaces could enhance upregulation of expression of the osteogenic markers and enhance alkaline phosphatase activity of BMSCs.	Bressel et al[66]
Laser beam treatment	DMLS discs were fabricated in an argon atmosphere with Yb fibre laser system.	Topographical cues of DMLS surfaces could enhance BMSC adhesion, as well as osteogenesis.	Zheng et al[67]
	The laser system was a Ti: Sa laser chain, which delivers 120 fs, 800 nm pulses at a repetition rate of 5 kHz.	BMSCs exhibited a more elongated, spindle-like morphology and higher spreading speeds on FS laser-modified surfaces.	Dumas et al[68]

Ti: Titanium; KOH: Potassium hydroxide; ALP: Alkaline phosphatase; OCN: Osteocalcin; HF: Hydrofluoric acid; HNO₃: Nitric acid; BMSC: Bone marrow-derived mesenchymal stem cell; NaOH: Sodium hydroxide; H₂O₂: Hydrogen peroxide; MAO: Micro-arc oxidation; O-PIII: Oxygen plasma immersion ion implantation; Ca: Calcium; Mg: Magnesium; RUNX₂: Runt-related transcription factor 2; DMLS: Direct metal laser sintering: Yb: Ytterbium; FS: Femtosecond.

Table 3 Covalent immobilization bioactive molecules to promote bone marrow mesenchymal stem cell adhesion, proliferation, and osteogenic differentiation

Bioactive molecules	Treatment process	Cell response	Ref.
Type I collagen	Titanium fiber meshes were treated with NaOH, followed by p-nitrophenyl chloroformate, and coated with collagen type I.	The modification of titanium fiber meshes can promote BMSC osteogenic differentiation.	van den Dolder et al[72]
	Covalent immobilization of collagen on titanium.	Greater regulation effect on BMSC osteogenesis compared to adsorptive immobilization.	Ao et al[74]
	Hyaluronic acid was immobilized on titanium surface by layer-by-layer technique.	BMSCs had more lamellipodia and adhered more closely to the covalently immobilized HyA surface.	Ao et al[78]
HyA	Covalent immobilization of RGD peptide on titanium surface.	RGD-functionalized titanium can improve early bone growth and matrix mineralization.	Elmengaard et al[87], Karaman et al[88]
RGD peptide	HBII-RGD was immobilized on the Ti surface.	HBII-RGD-functionalized Ti surfaces could stimulate BMSC differentiation and mineralization.	Guillem-Marti et al[90]
Growth factors	Covalently graft EGF and BMP-2 onto the oxide surfaces.	BMSC adhesion and proliferation were dramatically increased by covalently grafting EGF, but covalently grafted BMP-2 did not.	Bauer et al[92]
	PDGF-BB loading on titanium nanotube.	PDGF-BB functionalized surfaces significantly enhanced BMSC attachment and osteogenesis-related functions	Ma et al[98]

NaOH: Sodium hydroxide; BMSC: Bone marrow-derived mesenchymal stem cell; HyA: Hyaluronic acid; RGD: Arg-Gly-Asp; HBII-RGD: Heparin binding II-Arg-Gly-Asp; Ti: Titanium; EGF: Epidermal growth factor; BMP-2: Bone morphogenetic protein-2; PDGF-BB: Platelet-derived growth factor BB.

Table 4 Local control release of bioactive molecules to promote bone marrow mesenchymal stem cell adhesion, proliferation, and osteogenic differentiation

Bioactive molecule	Cell response	Ref.
L-DOPA	The new L-DOPA coating enhances the initial cell adhesion, mitochondrial activity, and proliferation of BMSCs on the titanium surface.	Kim et al[102]
DEX	The HA-Ti surfaces with DEX carrier system potently induce BMSC osteogenic differentiation in vitro.	Son et al[103]
SNs	The addition of SNs to the hydrogel formulation can promote bone formation when co-cultured with BMSCs.	Cheng et al[104]

L-DOPA: L-3,4-dihydroxyphenylalanine; BMSCs: Bone marrow-derived mesenchymal stem cells; HA: Hydroxyapatite; Ti: Titanium; DEX: Dexamethasone; SNs: Silicate nanoparticles.