Review Article

Direct Control of Stem Cell Behavior Using Biomaterials and Genetic Factors

Table 2

Maintenance of stemness using biomaterials.

Type of biomaterialsDetails of materialsType of cellsObservationRef.

Natural (nonsynthetic)Decellularized ECM of undifferentiated hMSCshMSCs
mASCs
Decellularized ECM of undifferentiated MSCs promoted self-renewal, colony formation, and stemness maintenance of hMSCs.[3841]
Decellularized tendon tissuehTSCsDecellularized tendon tissues enhanced self-renewal and stemness maintenance of hTSCs.[42]

HydrogelPolyacrylamide gels and PDMS stampshMSCsLow cytoskeletal tension was maintained by controlling substrate stiffness as cell spreading was restricted, thereby enhancing stemness. Polyacrylamide gels and PDMS stamps were used to regulate biophysical parameters.[43]
Alginate/GelMA hydrogelshBMSCs and GMSCsCompared to alginate hydrogels, alginate/GelMA hydrogels maintained stemness due to decreased hydrogel stiffness.[44]
Pullulan-collagen hydrogelmBMSCsBiomimetic hydrogel maintained stemness of mouse bone marrow-derived MSCs (mBMSCs) compared to tissue plate culture, resulting in enhanced viability after in vivo injection.[45]
RGD-modified poly(carboxybetaine) hydrogelhBMSCshMSCs formed 3D spheroids on the 5 μM RGD substrate, and the stemness was well maintained compared to 5 mM RGD substrate, which enhanced osteogenic differentiation.[46]

TopographyPCLhMSCsA surface nanopattern with 120 nm pits in a square arrangement with a center-center spacing of 300 nm enhanced stemness of hMSCs compared to the flat PCL surface.[47]
PDMShBMSCsA PDMS nanopattern 250 nm in depth, 350 nm in width, and with 700 nm pitch decreased hBMSC stemness compared to the flat surface control.[48]

Polymeric surface coatingPLL-coated surfacehBMSCsPLL-coated surface improved proliferation but retarded the replicative senescence of hBMSCs by increasing the S-phase.[49]
hHSCsPLL substrates increased the total number of hHSCs while stemness was maintained.[50]
PCL nanofiberhMSCsBone marrow collagen-mimetic PCL nanofiber matrices increased the expression of self-renewal factors and cell-cell interaction markers in hMSCs.[51]
PEG-PCL copolymerhMSCsPEG-PCL copolymer exhibited moderate surface repellency and induced aggregation of hMSCs, which promoted stemness and lowered intracellular ROS accumulation.[52]

Nanofibrous scaffoldEmu oil-loaded PCL/Coll nanofiberhASCsEmu oil-loaded nanofibers with higher tensile strength enhanced the expression of stemness, proliferation, and cell adhesion markers in hASCs compared to unloaded nanofibers.[53]
Gelatin nanofiberhMSCs3D culture of hMSC in a nanostructured electrospun gelatin patch maintained stemness of hMSCs for 3 weeks.[54]

ChitosanChitosan filmhASCThe chitosan film induced spheroid formation of hASCs with higher activities of self-renewal and colony formation, as well as significant upregulation of pluripotency marker expression.[56]
Chitosan film + hypoxiahUCBMSCThe chitosan film promoted spheroid formation of hUCBMSC under hypoxia than normoxia. HIF-1 additionally induced expression of stemness genes.[57]