Cell-reprogrammed three lineage-driven biomimetic devices yielding multiple skin appendage regeneration

The regeneration of skin appendages including hair follicles (HF), sweat glands (SwG), and sebaceous glands (SeG) is the prerequisite for functional skin repair. However, it is far from being done that how to induce in situ multiple skin appendage regeneration (MSAR) during wound healing. LGR6+ epidermal stem cells (EpSC) have been reported to generate all skin cell lineages. Given the advantages of biomaterials for tissue repair and their influence on cellular behavior that may regulate cell reprogramming, we developed a cell-reprogrammed three lineage-driven biomimetic device (TLBD) by using liposome nanoparticle drug delivery system, photo-responsive hyaluronic acid shell, positively charged polyamide and epidermal cell recruitment factor modification, microfluidic and photo-crosslinking techniques. The LGR6+ EpSC-activating chemical cocktail was the active center of TLBD, and polyamide for a positive charge that made TLBD match the wound electric fields. In vitro and in vivo studies demonstrated that TLBD can efficiently recruit endogenous epidermal cells and activate the LGR6+ EpSC property, prompting their response to wound microenvironment to differentiate into HF, SwG, and SeG lineages, thus facilitating re-epithelialization, wound healing and in situ MSAR. As a novel biomaterial used for in situ skin reprogramming, TLBD may have the great potential for functionally recapitulating damaged skin. [Display omitted] •Skin appendages are of great importance to skin function and homeostasis.•The cell-reprogrammed TLBD that can drive three skin lineage regeneration is developed.•TLBD foster in situ recruitment and activation of LGR6+ EpSC.•EGF and charged polyamide modifications were utilized within TLBD.•TLBD present a promise method for in situ skin reprogramming and functional wound healing.