Chemical and physical properties of regenerative medicine materials controlling stem cell fate

Figures & data

Figure 1. Factors influencing stem cell differentiation.

Figure 2. Major material variables that could influence the host response.

Table I. Some of the effects of material variables on cells.

Surface property	Description
Chemistry	Via protein adsorption: The chemical composition of a substrate surface dictates the type of bonds between protein and material surface. Hydrophobic surfaces enhance adsorption of proteins and conformational changes, while hydrophilic surfaces decrease protein adsorption and conformational changes.
Charge	Via protein adsorption: Opposite charges between the substrate surface and protein promote protein adsorption, while repulsion of like charges reduces protein adsorption.Directly: Negatively charged cell membranes adhere closely to positively charged surfaces, whereas contact occurs only at distinct points on near-neutral and negatively charged surfaces.
Surface energy	Via protein adsorption: Plays a major role in determining which proteins are adsorbed onto the surface.
Modulus	Directly: Modulus can cause changes in the cell shape, stiffness, or cytoskeletal architecture, which may further regulate cell responses. Secondly, cells sense and respond to substrate stiffness, possibly via mechanotransduction through an integrin–focal adhesion–cytoskeleton pathway and through non-integrin receptor-mediated adhesion.Via protein adsorption: Modulus can cause force-sensitive changes in the protein conformation.
Topography	Directly: Patterns and topography can influence cell size and shape, nuclear elongation and alignment, cell–cell interactions, and non-integrin/integrin positioning and focal adhesion formation, which may further regulate cell responses.Via protein adsorption: Increased surface roughness and topological features provide increased material surface area for protein adsorption.
Porosity	Important for the transport of oxygen, nutrients, and metabolic products, cell–cell interactions, and vascularization.Via protein adsorption: Porosity increases protein adsorption.Directly: Pore size directly regulates force production in cells.
Crystallinity	Via protein adsorption: A decrease in the surface layer crystallinity is considered to cause an increase in the protein adsorption.

These are generalized observations, and other mechanisms are possible.

Table II. Some effects of different surface chemistries on proteins and stem cells.

Functional group	Properties	Effect on proteins and stem cells
-CH3	Neutral; hydrophobic	Has high affinity/binding with fibrinogen; supports MSC maintenance (50)
-OH	Neutral; hydrophilic	Has relatively low affinity for plasma proteins (51); induces exposure of cell adhesive domains on fibronectin (52); does not support long-term adipogenic differentiation (50); promotes chondrogenic differentiation (53)
-NH2	Positive; hydrophilic	Has high affinity for fibronectin (54); most favourable for osteogenic differentiation (55)
-COOH	Negative; hydrophobic	Has increased affinity for fibronectin and albumin (55); promoted chondrogenic differentiation (55)

These are generalized observations and may vary depending on experimental condition.

Figure 3. Adsorption of tryptic soy broth visualized with a time of flight secondary ion mass spectrometer (ION-TOF, Münster, Germany) on A) patterned titanium and B) DLC. Background of the square patterns is silicon. The colour indicates the concentration of bound molecules and is the reason for different colours of silicon in the two samples shown.

Table III. Different optimal pore sizes and/or porosity ranges reported in the literature for stem cell differentiation to target cells/tissues.

Cell	Lineage	Pore size (μm)	Porosity (%)	Reference
Bone-marrow MSC	Osteogenic	100–300		(136)
Adipose MSC	Chondrogenic	370–400	96	(137)
hMSC-TERT4	Osteogenic	200	75	(138)
ESC	Haematopoietic	<150		(139)

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