Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing.

Journal Article (Journal Article)

Microporous annealed particle (MAP) scaffolds are flowable, in situ crosslinked, microporous scaffolds composed of microgel building blocks and were previously shown to accelerate wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow MAP degradation by switching the chirality of the crosslinking peptides from L- to D-amino acids. 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. MAP scaffolds recruit IL-33 type 2 myeloid cells, which is amplified 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.

Full Text

Duke Authors

Cited Authors

  • Griffin, DR; Archang, MM; Kuan, C-H; Weaver, WM; Weinstein, JS; Feng, AC; Ruccia, A; Sideris, E; Ragkousis, V; Koh, J; Plikus, MV; Di Carlo, D; Segura, T; Scumpia, PO

Published Date

  • April 2021

Published In

Volume / Issue

  • 20 / 4

Start / End Page

  • 560 - 569

PubMed ID

  • 33168979

Pubmed Central ID

  • PMC8005402

Electronic International Standard Serial Number (EISSN)

  • 1476-4660

International Standard Serial Number (ISSN)

  • 1476-1122

Digital Object Identifier (DOI)

  • 10.1038/s41563-020-00844-w


  • eng