Journal
COMPOSITES PART B-ENGINEERING
Volume 246, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.compositesb.2022.110239
Keywords
Stem cell spheroid; Granular hydrogel; Microgel; Wound healing; Macrophages
Funding
- National Natural Science Foundation of China [51973108, 51773113, 81971840]
- Shanghai Municipal Key Clinical Specialty [shslczdzk00901]
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This study developed a porous granular hydrogel that can efficiently produce and apply stem cell spheroids for wound treatment. The hydrogel possesses unique physical and chemical characteristics, enabling the proper release of growth factors from the spheroids to accelerate wound healing.
Stem cell spheroids possess higher viability and up-regulated paracrine function, showing advanced curative effect. However, the barrier of efficient spheroids preparation and application limits spheroids application in clinical. The present study developed an all-in-one porous granular hydrogel to not only produce numerous stem cell spheroids, but also apply the spheroids conveniently for wound treatment. Poly (sulfobetaine meth-acrylate) (PSBMA)-based microgels that cross-linked with disulfide bonds assembled, and further cross-linked by in-situ co-polymerized poly (N-isopropylacrylamide-co-sulfobetaine methacrylate) (P(NIPAM-co-SBMA)) to prepare porous composite granular hydrogel with bulk, shear-thinning, self-healing, hundred micron pores and low-fouling feature. Adipose-derived stem cells (ASCs) seeded into the porous composite granular hydrogel formed numerous spheroids inside the hundred micron pores. The porous composite granular hydrogel carrying produced ASC spheroids were spread onto the wound like creams. Then, PSBMA-based microgels dissolved quickly and spontaneously, forming extensive pores with the size less than 10 mu m, which ensured the effective release of growth factors produced by stem cell spheroids into the wound. In vivo evaluation confirmed that ASC spheroids up-regulated the secretion of anti-inflammatory factors and reparative growth factors, effectively inhibited the local inflammatory response of wounds in the early stage of wound, thus accelerating wound healing.
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