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

通过损伤相关分子途径 (DAMP) 分子附着提高生物材料植入物的耐受性

• 批准号: 10210393
• 负责人: Sarah E. Ewald
• 金额: $ 23.82万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10210393
• 关键词: Antibody Response; Automobile Driving; Bacteria; Biocompatible Materials; Biological; Biosensor; Cell Communication; Cell surface; Cells; Cellular Stress; Cessation of life; Chemistry; Cicatrix; Contraceptive Agents; Dermal; Detection; Environment; Exposure to; Family; Fibrosis; Flow Cytometry; Foreign Bodies; Gel; Geometry; Germ-Free; Glucose; Goals; Hair follicle structure; Homeostasis; Hydrogels; ITGAM gene; Immune; Immune response; Immune signaling; Immune system; Immunity; Impaired wound healing; Impairment; Implant; In Vitro; Individual; Infection; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Injectable; Injections; Leukocytes; Lipopolysaccharides; Mass Spectrum Analysis; Mediating; Molecular; Mus; Operative Surgical Procedures; Pathologic; Pathway interactions; Pattern; Pattern recognition receptor; Peptides; Resolution; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Site; Skin wound healing; Stromal Cells; Structure; Subcutaneous Injections; Surface; Technology; Tensile Strength; Testing; Thick; Tissues; Topical Antibiotic; Vascularization; Work; angiogenesis; cell type; cytokine; experimental study; glucose monitor; healing; high reward; high risk; implantation; improved; improved functioning; in vivo; infection risk; microbial; microbiota; microorganism; mouse model; novel; particle; pathogen; recruit; response; scaffold; subcutaneous; success; tissue-repair responses; tool; wound; wound environment; wound healing

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.

项目总结