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

Abstract

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.

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Published Version (Please cite this version)

10.1038/s41563-020-00844-w

Publication Info

Griffin, Donald R, Maani M Archang, Chen-Hsiang Kuan, Westbrook M Weaver, Jason S Weinstein, An Chieh Feng, Amber Ruccia, Elias Sideris, et al. (2021). Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing. Nature materials, 20(4). pp. 560–569. 10.1038/s41563-020-00844-w Retrieved from https://hdl.handle.net/10161/22757.

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Segura

Tatiana Segura

Professor of Biomedical Engineering

Tatiana Segura is a Professor of Biomedical Engineering, Neurology, and Dermatology at Duke University. She received her B.S. degree in Bioengineering from the University of California, Berkeley (UC Berkeley) and her doctorate in Chemical Engineering from Northwestern University.  She began her career in Biomaterials research during her doctoral work working with Prof. Lonnie Shea. She designed hydrogels for local non-viral gene delivery, a topic that she still works on today. She continued her Biomaterials training during her postdoctoral work with Jeffrey Hubbell. There she worked on the design of hydrogels and self-assembled polysulfides for gene delivery. She began her independent career at the University of California, Los Angeles (UCLA) in the Department of Chemical and Biomolecular Engineering reaching the title of Professor. At UCLA she participated actively in service culminating with her election as department Vice Chair and running the Graduate Program. At Duke she has continued to be heavily involved in service at the department, school, and university level. In only 5 years, she has Chaired 6 committees, and participated in at least 6 more, is the direct mentor to two young assistant professors, is the Co-director of the Center for Biotechnology and Tissue Engineering and serves as MPI of the T32 Biotechnology Training grant. Notably she is currently the Chair of the BME department Diversity Equity and Inclusion Committee. 

 

Prof. Segura’s research is centered on biomaterials and in engineering biomaterial-soft tissue interactions to promote repair and regeneration. Together with her lab members, she designs new biomaterial interventions that can promote brain plasticity after stroke, promote scarless healing in skin wounds, induce tolerance of transplanted skin, and promote constructive immune responses after biomaterial implantation. Currently, her lab has 12 graduate students, 4 postdoctoral scholars, 2 master students, 1 plastic surgery resident, 16 undergraduate students, one high school student, and one research associate. 

 

Professor Segura has received numerous awards and distinctions during her career, including being named a Senior Member of the National Academy of Inventors, receiving the Acta Biomaterialia Silver Medal, a CAREER Award from the National Science Foundation, a Outstanding Young Investigator Award from the American Society of Gene and Cell Therapy, and a National Scientist Development Grant from the American Heart Association. She was also named a Fellow of the American Institute for Medical and Biological Engineers (AIMBE). Professor Segura has published over 100 peer-reviewed papers and reviews and has over 10,000 citations. Her laboratory has been continuously funded since 2008 with several grants from the National Institutes of Health (NIH). 


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