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: 10399599
• 负责人: Sarah E. Ewald
• 金额: $ 19.77万
• 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/10399599
• 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; 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.

项目摘要 生物材料植入物成功的关键决定因素是它与宿主免疫系统的相互作用，该系统的相互作用 通常决定生物材料是否会生存和/或为宿主提供任何好处。每个生物材料 植入启动强度不同和宿主免疫激活的伤口环境取决于 通过模式识别受体（PRR）在细胞表面上的白细胞刺激。 PRR认识两个外国 病原体相关的分子模式（PAMP），在微生物（信号感染）和 由细胞应力，损伤或死亡引起的损伤相关分子模式（湿）（感染 独立的）。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 使用潮湿的分子可以大大减少纤维化生物植物反应，甚至可以抵消信号 炎性弹丸分子。我们发明了一个具有高度可调表面的生物材料平台 化学（允许潮湿的附着）和极低的固有纤维化生物材料反应称为 微孔退火粒子（MAP）脚手架。我们将使用地图的注射植物植物模型 脚手架以识别指导生产性伤口愈合和/或限制负面后果的潮湿 PAMP介导的生物材料排斥。这将对我们的理解产生重要的影响 伤口愈合环境，代表可以利用的工具的原理实验证明 改善伤口愈合，诱导疤痕重塑，并限制生物植入物部位的负免疫反应。

项目成果

Delivery of Dissociated Islets Cells within Microporous Annealed Particle Scaffold to Treat Type 1 Diabetes.

在微孔退火颗粒支架内递送解离的胰岛细胞来治疗 1 型糖尿病。

• DOI: 10.1002/adtp.202200064
• 发表时间: 2022
• 期刊: Advanced therapeutics
• 影响因子: 4.6
• 作者: Roosa,ColleenA;Ma,Mingyang;Chhabra,Preeti;Brayman,Kenneth;Griffin,Donald
• 通讯作者: Griffin,Donald