Cellular modulation by the mechanical cues from biomaterials for tissue engineering
Qiang Wei, Shenghao Wang, Feng Han, Huan Wang, Weidong Zhang, Qifan Yu, Changjiang Liu, Luguang Ding, Jiayuan Wang, Lili Yu, Caihong Zhu, Bin Li
Additional Table 1. Commonly-used biomaterials with various elasticities and their effects on cells.
Material Fabrication method Elasticity Effects on cell behaviours Cell source Reference
Alginate Alginate microspheres prepared by microfluidic technology with different elasticities and microarchitectures,controlled by calcium ion concentrations. 18, 32 kPa Elasticity and porosity regulated the fate of encapsulated MSCs through modulation of the nuclear factor-κB pathway MSCs 34
Chitosan-hyaluronic acid Porous chitosan-hyaluronic acid scaffolds of varied stiffness were fabricated using a phase separation method 1.41–27.7 kPa Increased matrix stiffness resulted in increased drug resistance of glioblastoma multiforme cells, and elevated expression of drug resistance-,hypoxia-, and invasion-related genes Glioblastoma multiforme cells 21
Dynamic protein hydrogels A Ru2+-mediated photochemical strategy was used to crosslink an aqueous solution of FGR(G-MEP-R)2 into a chemically-crosslinked protein hydrogel 6–20 kPa Human lung fibroblasts dynamically responded to changes of hydrogel mechanics in a reversible fashion, regulated by redox state Human lung fibroblasts 39
Fibrin-alginate Mechanical properties were tuneable via calcium chloride crosslinking 0.6–3.8 kPa Spreading of MSCs and endothelial cells was a function of alginate crosslinking density MSCs,
endothelial cells
22
Hyaluronic acid Methacrylated hyaluronic acid was synthesized to allow for crosslinking via Michael addition using the crosslinker dithiothreitol 0.2–4.5 kPa Human breast cancer cell (MDA-MB-231Br) adhesion, spreading, proliferation and migration were tightly regulated by the hydrogel stiffness MDA-MB-231Br 23
Polyacrylamide Stiffness of polyacrylamide gels was adjusted using different monomer-to-crosslinker formulations 2–32 kPa Cytoskeleton assembly and cell morphology were efficiently regulated by substrate stiffness HeLa cells 24
Poly
(dimethylsiloxane)
Poly(dimethylsiloxane) was used as the base material in which iron particles were embedded to create a magnetorheological elastomer, whose elasticity was controlled by the spacer distances between the magnet and the samples 10–55 kPa The softer substrates yielded more organised sarcomeres,and sarcomere formation was positively correlated with the degree of myocyte enrichment when using human-derived induced pluripotent stem cell cardiomyocytes Human-derived induced pluripotent stem cell cardiomyocytes,
cardiac fibroblasts
25
Polyurethane Controlling the crosslinking of tri-block copolymer and polycaprolactone triol yielded polyurethanes of varying elasticity 45.0–244.8 kPa Scaffolds with different stiffnesses stimulated the proliferation of different types of cells 3T3 fibroblasts,
MG63 cells
26
Silk fibroin Developed by introducing inert silk fibroin nanofibres within an enzyme crosslinked system of silk fibroin 9–60 kPa MSCs differentiated into endothelial, myoblast and osteoblast cells on the different elastic substrates MSCs 35
Silk fibroin-collagen The concentrations of both proteins was changed gradually while maintaining the ratio at 1:7, which resulted in a gradual change in stiffness at a fixed composition 0.1–20 kPa High rigidity allowed human MSCs to preserve all-directional spreading with polygonal shape. Soft substrates might not maintain the polygonal shape Human MSCs 27
Poly(ether carbonate urethane)urea Young’s modulus of scaffolds was tuned by adjusting the molecular weight of polydiol (soft segment) as well as the feed ratios of hard molecular segment to soft molecular segment 2.5–13.4 MPa Annulus fibrosus-derived stem cells showed strong tendencies to differentiate into various types of annulus fibrosus-like cells depending on the substrate elasticity Annulus fibrosus-derived stem cells 36, 102
PEG Stiffness was adjusted by adding various PEG monomers and the photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate 1.5–12.6 kPa The functional and molecular outputs of adult mouse ventricular myocytes were dependent on the PEG hydrogel stiffness Adult mouse ventricular myocytes 28
Poly(L-lactide-co-caprolactone)/poly(L-lactic acid) Fibre stiffness was controlled by altering the flow rates of the poly(L-lactic acid)-core and poly(L-lactide-co-caprolactone)-shell solutions. 14.7–2141.7 MPa Higher stiffness of the aligned fibrous substrates was found to significantly encourage the proliferation and migration of human umbilical artery smooth muscle cells Human umbilical arterial smooth muscle cells 29
GelMA hydrogels Prepared by photocrosslinking methacrylate gelatine and adjusting the stiffness by varying the concentration 3–180 kPa PC12 cell viability, adhesion, spreading and average neurite length were influenced by stiffness PC12 cells 30
GelMA/PEGDA hydrogels Prepared by photocrosslinking methacrylate gelatine and adjusting the stiffness with the crosslinker PEGDA 4, 40 kPa Increased matrix stiffness promoted osteogenic differentiation of MSCs MSCs 31
GelMA/Collagen hydrogels Prepared by mixing collagen and GelMA to form an interpenetrating network 2–12 kPa With the increase of matrix stiffness, the invasion and sprouting of the two cells decreased regardless of fibre content MDA-MB-231Br and endothelial cells 32
Alginate/GelMA hydrogels Prepared by mixing alginate and GelMA 6–13 kPa The expression level of MSC osteogenesis markers was enhanced with the increase in the matrix elastic modulus MSCs 33