Engineering Adaptive Immune Responses from Hydrogel Scaffolds to Promote Tissue Regeneration

摘要 生物材料支架是一种很有前途的基于材料的组织再生方法。我们之前 开发的微孔退火颗粒(MAP)水凝胶-一种可流动的、基于微粒的水凝胶，其中 相邻的水凝胶颗粒在原位连接起来，形成一个多孔的支架，加速伤口愈合。 最近，我们发现了一种相对简单的将交联肽从L对映体修饰为D-交联肽的方法。 对映体可导致大量皮肤再生，而这种再生仅在自适应 免疫系统完好无损。进一步的研究表明，尽管D-手性多肽是一种较差的激活剂。 巨噬细胞天然免疫信号、D-手性多肽内MAP(D-MAP)诱导的显著抗原特异性 豁免权。在这个提案中，我们将进一步研究我们的D-map材料激活自适应 免疫系统，并导致皮肤组织再生。目标1将重点放在进一步了解 先天免疫系统和MAP支架微结构决定巨噬细胞表型的能力。目标2 将专注于测试我们的假设，即适应性免疫系统被我们的材料激活并导致 创面再生愈合。AIM 3将研究其他生物材料方法来呈现D-肽和 进一步控制免疫系统的激活。

Summary 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. Recently, we found that a relatively simple modification to the crosslinker peptide from L-enantiomer to D- enantiomer resulted in substantial skin regeneration and that this regeneration only occurs when the adaptive immune system is intact. Further investigation revealed that although D-chiral peptides were poor activators of macrophage innate immune signaling, D-chiral peptides within MAP (D-MAP) elicited significant antigen-specific immunity. In this proposal, we will further investigate the ability of our D-MAP material to activate the adaptive immune system and lead to skin tissue regeneration. Aim 1 will focus on further understanding any role of the innate immune system and the ability of MAP scaffold microstructure to dictate macrophage phenotype. Aim 2 will focus on testing our hypothesis that the adaptive immune system is activated by our material and leads to regenerative wound healing. Aim 3 will investigate other biomaterial approaches to present D-peptides and further control immune system activation.