Griffin, Donald RDonald RGriffinArchang, Maani MMaani MArchangCHEN-HSIANG KUANWeaver, Westbrook MWestbrook MWeaverWeinstein, Jason SJason SWeinsteinFeng, An ChiehAn ChiehFengRuccia, AmberAmberRucciaSideris, EliasEliasSiderisRagkousis, VasileiosVasileiosRagkousisKoh, JaekyungJaekyungKohPlikus, Maksim VMaksim VPlikusCarlo, Dino DiDino DiCarloSegura, TatianaTatianaSeguraScumpia, Philip OPhilip OScumpia2023-03-272023-03-272020-05-3026928205https://scholars.lib.ntu.edu.tw/handle/123456789/629776Biomaterial scaffolds represent a promising approach for material-based tissue regeneration. We previously developed microporous annealed particle (MAP) hydrogels - a flowable, microparticle-based hydrogel in which neighboring hydrogel particles are linked in situ to form a porous scaffold that accelerates wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow scaffold degradation by switching the chirality of the crosslinking peptides from L-peptides to D-peptides. Unexpectedly, despite showing the predicted slower enzymatic degradation in vitro, D-peptide crosslinked MAP hydrogel (D-MAP) hastened material degradation in vivo and imparted significant tissue regeneration to healed cutaneous wounds, including increased tensile strength and hair neogenesis. By themselves, D-chiral peptides were poor activators of macrophage innate immune signaling in vivo, but MAP particles elicit IL-33 type 2 myeloid cell recruitment which is amplified in vivo in the presence of D-peptides. Remarkably, D-MAP elicited significant antigen-specific immunity against the D-chiral peptides, and an intact adaptive immune system was required for the hydrogel-induced skin regeneration. These findings demonstrate that the generation of an adaptive immune response from a biomaterial is sufficient to induce cutaneous regenerative healing despite faster scaffold degradation. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.enActivating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healingother10.1101/2020.05.27.1173172-s2.0-85102909024http://www.scopus.com/inward/record.url?eid=2-s2.0-85102909024&partnerID=MN8TOARS