Biomimetic cell-adhesive ligand-functionalized peptide composite hydrogels maintain stemness of human amniotic mesenchymal stem cells

In vivo,stem cells reside in a three-dimensional(3D)extracellular microenvironment in which complicated biophysical and biochemical factors regulate their behaviors.Biomimicking of the stem cellmatrix interactions is an ideal approach for controlling the stem cell fate.This study investigates the effects of the incorporation of cell-adhesive ligands in 3D self-assembling peptide hydrogels to modulate stem cell survival,proliferation,maintenance of stemness,and osteogenic differentiation.The results show that the composite hydrogels were non-cytotoxic and effective for maintaining human amniotic mesenchymal stem cell(hAMSC)survival,proliferation and phenotypic characterization.The expression levels of pluripotent markers were also upregulated in the composite hydrogels.Under inductive media conditions,mineral deposition and mRNA expression levels of osteogenic genes of hAMSCs were enhanced.The increasing expression of integrin aand b-subunits for hAMSCs indicates that the ligandintegrin interactions may modulate the cell fate for hAMSCs in composite hydrogels.

Neuro-regenerative imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α promote stem cell differentiation and repair focal brain injury

Brain tissues that are severely damaged by traumatic brain injury(TBI)is hardly regenerated,which leads to a cavity or a repair with glial scarring.Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage,whose use is,whereas,limited by the low survival rate and differentiation efficiency of stem cells.To approach this problem,we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate(GelMA-imid).In addition,polydopamine(PDA)nanoparticles were used as carrier for stromal-cell derived factor-1(SDF-1α).GelMA-imid hydrogel loaded with PDA@SDF-1αnanoparticles and human amniotic mesenchymal stromal cells(hAMSCs)were injected into the damaged area in an in-vivo cryogenic injury model in rats.The hydrogel had low module and its average pore size was 204.61±41.41 nm,which were suitable for the migration,proliferation and differentiation of stem cells.In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1αcould promote the migration of hAMSCs to injury site and their differentiation into nerve cells.The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model.Additionally,histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells.In summary,the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells,and showed great application potential for the physiological recovery of TBI.