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.

微孔退火颗粒 (MAP) 支架是可流动的、原位交联的微孔支架，由微凝胶构建块组成，之前已被证明可以加速伤口愈合。为了在支架降解前促进更广泛的组织向内生长，我们旨在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期的较慢酶促降解，但d肽交联 MAP 水凝胶（d-MAP) 加速体内材料降解，并为愈合的皮肤伤口带来显着的组织再生，包括增加的拉伸强度和毛发新生。MAP 支架募集 IL-33 2 型骨髓细胞，该细胞在存在d肽的情况下被放大。值得注意的是，d -MAP 引发了针对d-手性肽的显着抗原特异性免疫，并且水凝胶诱导的皮肤再生需要完整的适应性免疫系统。这些发现表明，尽管支架降解速度更快，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。