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

点击翻译按钮获取中文摘要

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.