Biomaterial scaffolds represent a promising approach for material-based tissue regeneration. We previously developed microporous annealed particle (MAP) hydrogels - a flowable, microparticle-based hydrogel in which neighboring hydrogel particles are linked in situ to form a porous scaffold that accelerates wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow scaffold degradation by switching the chirality of the crosslinking peptides from L-peptides to D-peptides. 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. By themselves, D-chiral peptides were poor activators of macrophage innate immune signaling in vivo, but MAP particles elicit IL-33 type 2 myeloid cell recruitment which is amplified in vivo 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.

中文翻译：

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激活来自水凝胶支架的适应性免疫反应可再生伤口愈合。

生物材料支架代表了一种基于材料的组织再生的有前途的方法。我们先前开发了微孔退火颗粒（MAP）水凝胶-一种可流动的基于微粒的水凝胶，其中相邻的水凝胶颗粒就地连接在一起，从而形成可加速伤口愈合的多孔支架。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肽转换为D肽来减缓支架降解。出乎意料的是，尽管显示出预期的体外酶降解速度较慢，但​​D肽交联的MAP水凝胶（D-MAP）加速了体内的材料降解，并为愈合的皮肤伤口带来了显着的组织再生，包括增加的拉伸强度和头发新生。通过他们自己，D-手性肽是体内巨噬细胞固有免疫信号的弱活化剂，但是MAP颗粒引起IL-33 2型髓样细胞募集，该募集在D肽存在下在体内扩增。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，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，但是从生物材料产生适应性免疫应答仍足以诱导皮肤再生愈合。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，但是从生物材料产生适应性免疫应答仍足以诱导皮肤再生愈合。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，但是从生物材料产生适应性免疫应答仍足以诱导皮肤再生愈合。