Chemical and Biomolecular Engineering Department, University of California, Los Angeles, CA, USA.
Departments of Biomedical Engineering and Chemical Engineering, University of Virginia, Charlottesville, VA, USA.
Nat Mater. 2021 Apr;20(4):560-569. doi: 10.1038/s41563-020-00844-w. Epub 2020 Nov 9.
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，先前已被证明可加速伤口愈合。为了在支架降解之前促进更广泛的组织向内生长，我们旨在通过将交联肽的手性从 L-转变为 D-氨基酸来减缓 MAP 的降解。出乎意料的是，尽管 D-肽交联 MAP 水凝胶 (D-MAP) 在体外表现出预期的更缓慢的酶降解，但它在体内加速了材料的降解，并赋予了愈合的皮肤伤口显著的组织再生能力，包括增加的拉伸强度和毛发新生。MAP 支架募集 IL-33 型 2 髓样细胞，在 D-肽存在下会被放大。值得注意的是，D-MAP 引发了针对 D-手性肽的显著抗原特异性免疫，而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，尽管支架降解更快，但从生物材料产生适应性免疫反应足以诱导皮肤再生性愈合。
