Copyright ©The Author(s) 2022.
World J Diabetes. Nov 15, 2022; 13(11): 949-961
Published online Nov 15, 2022. doi: 10.4239/wjd.v13.i11.949
Table 1 Summary of studies regarding therapy combining hydrogels and stem cells for diabetic wound healing
Stem cell information, types, dosage in cells/wound
Hydrogel composition
Hydrogel types
Application methods
Wound size diameter, location
Full re-epithelialization efficiency
UMSCs from human, xenogeneic, 1 × 106Self-assembled nanopeptide hydrogels based on RADA16-I, RGD, and KLT peptide solutionsSelf-assembled nanopeptide hydrogels with easy biomimetic functionalizationCells were encapsulated into the in situ forming hydrogelsNOD/SCID mice8 mm, dorsal10 dAccelerated skin wound healing by inhibiting inflammation and promoting angiogenesis[14]
BMSCs from rats, allogenic, 2 × 105N-chitosan/ HA-ALD hydrogelHemostasis and antimicrobial hydrogelsCells were encapsulated into the in situ forming hydrogelsSTZ-induced diabetic rats5 mm, foot12 dPromoted wound healing; stimulated the secretion of growth factors from rBMSCs, and modulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization[37]
ADSCs from human, xenogeneic, 3 × 105GG-HA spongy hydrogelVascularization hydrogelsCells were seeded onto the top of spongy-like hydrogel sheetsSTZ-induced diabetic mice9 mm, dorsal4 wkAccelerated excisional skin wound healing; induced the healing phase switch from the inflammatory to the proliferative phase; presented a thicker epidermis with a high number of proliferative keratinocytes in the basal layer; increased the number of intraepidermal nerve fibers in the regenerated epidermis[41]
BMSCs from rabbits, allogenic, 1 × 106SNAP-loaded chitosan-PVA hydrogelVascularization hydrogelsCells were intradermally injected and topically covered with hydrogel sheetsAlloxan monohydrate induced diabetic rabbits20 mm, dorsal14 dAugmented the wound closure, decreased inflammation, and upregulated expression of CD31, VEGF and TGFβ-1; promoted angiogenesis by forming new capillaries and improving the microvascular and vessel maturation; showed an abundant expression of collagen type I on day 14[44]
ADSCs from human, xenogeneic, 5 × 105Curcumin-incorporated 3D bioprinting GelMA hydrogelAntioxidant hydrogelsCells were encapsulated into hydrogel sheetsSTZ-induced diabetic nude mice15 mm, dorsal21 dPromoted wound healing; improved hADSCs apoptosis and increased the amount of collagen[46]
ADSCs from human, xenogeneic, 2.5 × 105hDAM hydrogelIntact ECM-derived hydrogels from living tissuesCells were suspended in the in situ forming hydrogelsKK/Upj-Ay/J mice (diabetic mice)8 mm, dorsal14 dAccelerated wound closure and improved skin architecture regeneration, including better restoration of cutaneous appendages, increase of dermis thickness, and augmenting neovascularization[62]
UMSCs from human, xenogeneic, 5 × 106GelMA/Chi-C hydrogelVascularization hydrogelsCells were mixed with the in situ forming hydrogelsDiabetic mice (db/db)8 mm, dorsal14 dPromoted the wound healing process by inhibiting protein expression of TNF-α and IL-1β to decrease inflammation. Accelerated angiogenesis and re-epithelialization, promoted collagen deposition, and induced regeneration of skin appendages such as hair follicles[63]
PDSCs from human, xenogeneic, 1 × 106Chitosan/collagen/β-GP hydrogelThermosensitive and pH-responsive hydrogels3D spheroids were encapsulated in the in situ forming hydrogelsDiabetic mice (db/db)7 mm, dorsal3 wkAccelerated wound closure by enhancing angiogenesis and paracrine effects. The hydrogel provided an environment favorable for the attachment and proliferation of encapsulated hPDSCs, accelerating cell proliferation and paracrine factor secretion[67]
ADSCs from rats, allogenic, 5 × 105Gelatin hydrogelAdaptive hydrogel microspheres with degradation rates well-matched to tissue regenerationHydrogel microspheresSTZ-induced diabetic rats8 mm, dorsal14 dSignificantly accelerated wound healing by promoting M2 macrophage polarization, collagen deposition, angiogenesis associated with peripheral nerve recovery, and hair follicle formation. The microspheres well embedded in the tissue, exhibited good biocompatibility and adaptive biodegradation rates[77]
BMSCs from human, xenogeneic, 5 × 105PEGDA hydrogelBioinert synthetic hydrogelsCells were encapsulated into hydrogel sheetsGenetically diabetic mice (BKS.Cg-m +/+Leprdb/J)1 cm × 1 cm1, dorsal14 dAccelerated wound healing; the co-encapsulation of hBMSCs and insulin secreting cells resulted in healing wounds without scab or scar[79]
ADSCs from human, xenogeneic, 3 × 105PEG-gelatin hydrogelVascularization hydrogelsCells were mixed with the in situ forming hydrogelsDiabetic mice (db/db)6 mm, dorsal15 dSignificantly accelerated wound closure; the encapsulated cells attached and diffused well inside the hydrogel, improving cell retention in vivo; reduced inflammatory cell infiltration and enhanced neovascularization[80]