Cocktail Cell‐Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration

Abstract

The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of “seeding and harvest”, are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast‐to‐DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two‐pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.

Advances and applications of biomimetic biomaterials for endogenous skin regeneration

“…By combining the liposome nanoparticles, photo-responsive hydrogel shell, microfluidic and photo-crosslinking techniques, the AHFS hydrogel/microspheres drug delivery system delivered sever small molecule drugs to fibroblasts and successfully in situ reprogramed them to dermal papilla cells (DPCs). The results of following experiments indicated that the AHFS system could activate the PI3K/AKT pathway, promoting wound healing and endogenous hair follicles regeneration, also could inhibit the transformation of fibroblasts to myofibroblasts and inhibit scar formation [ 256 ]. Biswas et al successfully delivered myoblast determination protein 1 (MYOD1) transcription factor in the cell nucleus of myoblast cells by PEG nanoparticle, and then reprogramed myoblast differentiation into skeletal, cardiac or smooth-muscle cells [ 257 ].…”