Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing.
Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing.
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DOI：
10.1038/s41563-020-00844-w
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发表时间：
2021-04
期刊：
影响因子：
41.2
通讯作者：
Scumpia PO
中科院分区：
文献类型：
--
作者：
Griffin DR;Archang MM;Kuan CH;Weaver WM;Weinstein JS;Feng AC;Ruccia A;Sideris E;Ragkousis V;Koh J;Plikus MV;Di Carlo D;Segura T;Scumpia PO
微孔退火颗粒（MAP）支架是由微凝胶构建块组成的可流动的、原位交联的微孔支架，并且先前显示出加速伤口愈合。为了在支架降解之前促进更广泛的组织向内生长，我们的目标是通过将交联肽的手性从L-氨基酸转换为D-氨基酸来减缓MAP降解。出乎意料的是，尽管在体外显示出预测的较慢的酶促降解，但D-肽交联的MAP水凝胶（D-MAP）加速了体内材料降解，并赋予愈合的皮肤伤口显著的组织再生，包括增加的拉伸强度和毛发新生。MAP支架募集IL-33 2型髓样细胞，其在D-肽存在下扩增。值得注意的是，D-MAP引起了显着的抗原特异性免疫对D-手性肽，和一个完整的适应性免疫系统所需的水凝胶诱导的皮肤再生。这些发现表明，尽管支架降解更快，但生物材料产生的适应性免疫反应足以诱导皮肤再生愈合。
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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