Direct Control of Stem Cell Behavior Using Biomaterials and Genetic Factors

Table 3

Direct differentiation using biomaterials.

Property	Type of materials	Differentiation	Details of materials	Comments	Ref.
Composition	Scaffold	Chondrogenesis	Cellulose/silk blend	Growing MSCs on a specific blend combination of cellulose and silk in a 75 : 25 ratio significantly upregulated expression of chondrogenic markers.	[120]
		myogenesis	ECM-like porous scaffold of poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBHV)/gelatin blends	PHBHV/gelatin constructs mimicking myocardial structural properties.	[121]
		Chondrogenesis/osteogenesis	Collagen-glycosaminoglycan	Collagen-chondroitin sulphate (CCS) scaffolds enhanced osteogenesis while collagen-hyaluronic acid (CHyA) scaffolds enhanced chondrogenesis.	[122]
		Cardiomyogenesis	Carbon nanotube/poly-L-lactide acid (PLA) nanofiber	The two-pronged carbon nanotube template provided a biomimetic electroactive cue, thereby directing MSC differentiation.	[13]
	Decellularized tissues	Chondrogenesis	Cartilage extracellular matrix-derived particles (CEDPs)	Microtissue aggregates (BMSCs and CEDPs (263 ± 48 μm) cocultured in a rotary cell culture system) showed a more rapid restoration of joint functions with superior cartilage repair compared to the control groups in vivo.	[3]
		Osteogenesis	Calcium phosphate nanoparticles and demineralized bone matrix (DBM) particles incorporated into injectable polyHIPE	PolyHIPE compositions with BMSCs promoted osteogenic differentiation through upregulation of bone-specific marker expression compared to a time zero control.	[4]
	Bioinorganics	Osteogenesis	3D graphene foams (GFs)	3D GF culture platforms maintained stem cell viability and promoted osteogenic differentiation.	[123]
	Biomimetics	Chondrogenesis	Polyacrylate substrate functionalized with RGD peptide	Biomimetic polyacrylate substrates can direct chondrogenic differentiation of mMSCs, hMSCs, and mouse KSCs in the absence of exogenous TGF-bs.	[124]
Substrate stiffness	Hydrogels	Osteogenesis/neurogenesis	Polyacrylamide (0.5~40 kPa) hydrogel substrate	MSCs on soft (~0.5 kPa) gels promoted expression of neurogenesis markers while MSCs on stiff (~40 kPa) substrates elevated expression of osteogenesis markers. Transfer of MSCs from soft to stiff or stiff to soft substrates led to a switch in the lineage specification.	[60]
		Osteogenesis/chondrogenesis	Methyl acrylate/methyl methacrylate (18–72 MPa) hydrogel substrate	Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with . MSCs on lower stiffness gels express elevated chondrogenesis markers while MSCs on the higher stiff substrates express elevated osteogenesis markers.	[61]
		Angiogenesis	Gelatin hydrogel conjugating enzymatically cross linkable hydroxyphenyl propionic acid (GHPA)	GHPA as a promising soluble factor-free cell delivery template induced endothelial differentiation of MSCs with robust neovasculature formation with favorable host responses.	[63]
		Angiogenesis	PEGylated fibrin 3D matrix	Endothelial differentiation of MSC was induced by the 3D PEGylated fibrin matrix.	[64]
Surface topograpy	Film	Neurogenesis/myogenesis	Micropatterned poly(lactic-co-glycolic acid) (PLGA) ultrathin film	Micropattering: microsize lanes of 20 μm width separated by 40 μm wide grooves on a PLGA ultrathin film (16.3 ± 1.5 μm)	[66]
	Hydrogel	Adipogenesis/neurogenesis	Hydrazine-treated polyacrylamide gel (circular and anisotropic geometry)	Cells cultured in small circular islands show elevated expression of adipogenesis markers while cells that spread in anisotropic geometries elevated expression of neurogenic markers.	[67]
	Bioinorganics	Osteogenesis/neurogenesis	Graphene/electrical stimulation	Specific combinations of nonbiological inputs—material type, electrical stimulation, and physical patterns on graphene substrates regulated hMSC lineage specification.	[70]
		Osteogenesis	Nanotubule-shaped titanium oxide surface	Small (30 nm diameter) nanotubes promoted cell adhesion without noticeable differentiation, whereas larger (70 to 100 nm diameter) nanotubes elicited a dramatic stem cell elongation (10-fold increased), which induced cytoskeletal stress and selective differentiation into osteoblast-like cells.	[71]
		Osteogenesis	Titanium substrate	Surface microstructure and surface energy from microstructured Ti substrate were able to direct osteogenic differentiation of mesenchymal stem cells.	[72]