Improving Biomaterial Implant Tolerance with Damage-Associated Molecular Pathway (DAMP) Molecule Attachment

项目总结 生物材料植入成功的一个关键决定因素是它与宿主免疫系统的相互作用，这 通常决定生物材料是否会存活和/或为宿主提供任何好处。每种生物材料 植入启动了不同强度的创伤环境，宿主免疫的激活依赖于 通过细胞表面的模式识别受体(PRRs)刺激白细胞。PRR承认这两个外国人 病原体相关分子模式(PAMP)，在微生物(信号感染)和 由细胞应激、损伤或死亡(感染)引起的损伤相关分子模式(DAMP) 独立)。由于它们在非病理组织反应中的作用，我们认为植入物的表面处理 含湿分子可以大大降低纤维化的生物植入反应，甚至可以抵消信号 更具炎症性的PAMP分子。我们发明了一种表面高度可调的生物材料平台 化学(允许潮湿附着)和极低的固有纤维化生物材料反应称为 微孔退火颗粒(MAP)支架。我们将使用注射-植入MAP的小鼠模型 脚手架，以确定指示创面有效愈合和/或限制负面后果的湿气 PAMP介导的生物材料排斥反应。这将对我们理解 伤口愈合环境，并代表可被利用的工具的原理实验的证明 促进伤口愈合，诱导疤痕重塑，并限制生物植入部位的负面免疫反应。

PROJECT SUMMARY A key determinant of the success of a biomaterial implant is its interactions with the host immune system, which often determines whether the biomaterial will survive and/or provide any benefit to the host. Every biomaterial implantation initiates a wound environment of varying intensity and activation of host immunity is dependent on leukocyte stimulation via pattern recognition receptors (PRRs) on the cell surface. PRRs recognize both foreign pathogen-associated molecular patterns (PAMPs) that are common on microorganisms (signaling infection) and damage-associated molecular patterns (DAMPs) that arise from cell stress, damage, or death (infection independent). Due to their role in a non-pathological tissue response, we believe surface treatment of implants with DAMP molecules can greatly diminish fibrotic bioimplant response and can even counteract the signaling of more inflammatory PAMP molecules. We have invented a biomaterial platform with highly tunable surface chemistry (to allow DAMP attachment) and an extremely low inherent fibrotic biomaterial response called Microporous Annealed Particle (MAP) scaffolding. We will use a murine model of injection-implant of the MAP scaffolding to identify DAMPs that instruct productive wound healing and/or limit the negative consequences PAMP-mediated biomaterial rejection. This will have important consequences for our understanding of the wound healing environment and represent proof of principle experiments for a tool that can be harnessed to improve wound healing, induce scar remodeling, and limit negative immune responses at bioimplant sites.