Multifunctional Single‐Component Polypeptide Hydrogels: The Gelation Mechanism, Superior Biocompatibility, High Performance Hemostasis, and Scarless Wound Healing

Abstract Polymeric hydrogels have been increasingly studied for wound sealants, adhesives, hemostats, and dressings, however, multi‐component gelation, adhesion‐causing tissue damage, inefficient hemostasis, and skin scarring in wound healing hamper their advances. So it is urgent to develop multifunctional single‐component polymeric hydrogels with benign tissue detachment, high performance hemostasis, and scarless wound healing attributes. Herein, a dopamine‐modified poly( l ‐glutamate) hydrogel at an ultralow concentration of 0.1 wt% is serendipitously constructed by physical treatments, in which a gelation mechanism is disclosed via oxidative catechol‐crosslinking and sequential dicatechol‐carboxyl hydrogen‐bonding interactions. The covalent/H‐bonding co‐crosslinked and highly negative‐charged networks enable the polypeptide hydrogels thermo‐, salt‐, urea‐resistant, self‐healing, injectable, and adhesive yet detachable. In vitro and in vivo assays demonstrate they have superior biocompatibility with ≈0.5% hemolysis and negligible inflammation. The polypeptide/graphene oxide hybrid hydrogel performs fast and efficient hemostasis of 12 s and 1.4% blood loss, surpassing some hydrogels and commercial counterparts. Remarkably, the polypeptide hydrogels achieve scarless and full wound healing and regenerate thick dermis with some embedded hair follicles within 14 days, presenting superior full‐thickness wound healing and skin scar‐preventing capabilities. This work provides a simple and practicable method to construct multifunctional polypeptide hemostatic and healing hydrogels that overcome some above‐mentioned hurdles.