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Effects of Poly(ethylene glycol) Immunogenicity on Implant Biocompatibility

聚乙二醇免疫原性对植入物生物相容性的影响

基本信息

批准号：
10798522
负责人：
Daniel Alge
金额：
$ 2.97万
依托单位：
TEXAS ENGINEERING EXPERIMENT STATION
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10798522
关键词：
Acrylamides Address Adhesives Affect Alkynes Animal Model Animals Antibodies Azides Biocompatible Materials Blood Tests Cell Adhesion Cell Therapy Cell secretion Cells Chemistry Complement Activation Cosmetics Drug Delivery Systems Enzymes Esters Exposure to Flow Cytometry Foreign Bodies Formulation Funding Future Histology Hydrogels Immune Immune response Immunize Immunohistochemistry Immunologics Immunology Implant Individual Inflammation Inflammatory Infusion procedures Investigation Knowledge Ligands Longitudinal Studies Magnetic Resonance Imaging Marketing Medical Device Modulus Mus Outcome Peptides Pharmaceutical Preparations Pharmacologic Substance Polymers Population Predisposition Property Proteins Reporting Research Risk Safety Study of magnetics Sulfhydryl Compounds Testing Therapeutic United States National Institutes of Health Variant Work adaptive immune response biomaterial compatibility chemical property crosslink design ethylene glycol experimental study immunogenic immunogenicity implantation in vivo in vivo evaluation inflammatory marker interest intravenous administration methacrylamide non-invasive imaging patient screening physical property response subcutaneous

项目摘要

PROJECT SUMMARY Poly(ethylene glycol) (PEG) based hydrogels are widely used in medical devices and are being studied for the delivery of protein and cellular therapeutics. While these biomaterials are widely regarded as biologically inert, concerns over PEG’s immunogenicity have emerged in recent years. It has been estimated that 20-30% of the population has antibodies against PEG due to exposure via pharmaceuticals, cosmetics, and other PEG- containing products. While an anti-PEG immune response has been found to reduce the efficacy of intravenously administered PEGylated drugs, the impact on the biocompatibility of PEG hydrogels has not previously been studied and is currently unknown. To address this knowledge gap, this project has two Specific Aims that encompass comprehensive in vivo testing to evaluate the host response to PEG hydrogels of varying physical and chemical properties. In these experiments, PEG hydrogels will be implanted subcutaneously in mice, and the host response will be evaluated at early, intermediate, and late timepoints using histology, immunohistochemistry, flow cytometry, and blood testing. The key comparison in these experiments will be between animals conditioned to mount an anti-PEG response and immunologically naïve controls. The project has two Specific Aims. Aim 1 focuses on PEG hydrogel formulations that lack hydrolytically and enzymatically cleavable linkers. Hydrogels that differ in modulus, crosslinking chemistry, and functionalization with cell-adhesive peptides will be systematically studied. Aim 2 focuses on PEG hydrogel formulations that contain hydrolytically and enzymatically degradable linkers. In addition to evaluating the host response, the impact of the anti-PEG immune response on the in vivo degradation rate of these hydrogels will be investigated via non-invasive imaging in a longitudinal study. The results of this project will either alleviate concerns over PEG immunogenicity for biomaterial implants or motivate future investigations on strategies to mitigate its effects.

项目总结