Impact of the Anti-PEG Response on the Efficacy of PEG Hydrogel-Mediated Bone Regeneration

抗 PEG 反应对 PEG 水凝胶介导的骨再生功效的影响

• 批准号: 9890921
• 负责人: Daniel Alge
• 金额: $ 19.52万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-10 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9890921
• 关键词: Address; Affinity; Animals; Antibodies; Antigens; Binding; Biocompatible Materials; Biological; Biomedical Engineering; Bone Regeneration; Bone Tissue; Calvaria; Clinic; Control Animal; Control Groups; Cosmetics; Data; Defect; Development; Drug Delivery Systems; Ensure; Enzyme-Linked Immunosorbent Assay; Event; Exposure to; Funding; Future; Growth Factor; Histology; Hydrogels; Immune response; Immunohistochemistry; Immunologics; Immunology; Implant; In Vitro; Incidence; Individual; Intravenous; Investigation; Knowledge; Measurement; Mediating; Medicine; Modeling; Molecular; Mus; Outcome; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Polymers; Population; Proteins; Reporting; Research; Testing; Texas; Therapeutic; Tissue Engineering; Treatment Efficacy; United States National Institutes of Health; Universities; Vertebral column; X-Ray Computed Tomography; base; bone healing; bone morphogenetic protein 2; ethylene glycol; experimental study; immunogenicity; immunoreaction; implantation; in vivo; in vivo Model; innovation; interest; knowledge translation; mid-career faculty; negative affect; professor; regenerative therapy; response; scaffold; subcutaneous; tissue regeneration

PROJECT SUMMARY Poly(ethylene glycol) (PEG) based hydrogels are promising and versatile materials for the delivery of protein and cellular therapeutics for bone tissue engineering. However, concerns over PEG’s immunogenicity have emerged in recent years, and it has been estimated that as much as 25% of the population has antibodies against PEG due to exposure via pharmaceuticals, cosmetics, and other PEG-containing products. While the anti-PEG response has been found to reduce the efficacy of intravenously administered PEGylated drugs, its impact on the efficacy of regenerative therapeutics delivered from PEG hydrogels has not previously been studied and is unknown. The objective of this project is to address this knowledge gap through in vivo experimentation comparing animals conditioned to mount an anti-PEG response to immunologically naïve controls. Aim 1 consists of a subcutaneous implantation study in mice, which will elucidate the effects of the anti-PEG immune reaction on the fundamental biological response to PEG hydrogels. Aim 2 involves a bone tissue engineering study in which the impact of the anti-PEG response on hydrogel-mediated delivery of bone morphogenetic protein-2 (BMP-2) will be tested in a murine calvarial defect model. Quantitative measurements of bone healing compared to control animals will be used to determine whether bone healing is negatively affected. The results of this exploratory project will either alleviate concerns over PEG immunogenicity for tissue engineering or motivate future investigations on strategies to mitigate its effects.

项目摘要 聚乙二醇（PEG）水凝胶是一种很有前途的蛋白质载体材料 和骨组织工程的细胞治疗学。然而，对PEG免疫原性的担忧已经引起了人们的关注。 近年来出现，据估计，多达25%的人口有抗体， 由于通过药物、化妆品和其他含PEG的产品暴露，而 已经发现抗PEG应答降低静脉内施用的PEG化药物的功效，其 对从PEG水凝胶递送的再生治疗剂的功效的影响以前还没有被 研究和未知。本项目的目标是通过体内研究来解决这一知识差距。 比较适应于产生抗PEG应答的动物与免疫学上幼稚的动物的实验 对照目的1包括小鼠皮下植入研究，其将阐明 抗PEG免疫反应对PEG水凝胶的基本生物反应。目标2涉及骨 组织工程研究，其中抗PEG反应对水凝胶介导的骨递送的影响 将在鼠颅骨缺损模型中测试形态发生蛋白-2（BMP-2）。定量测量 将使用与对照动物相比的骨愈合的百分比来确定骨愈合是否是负性的。 影响。该探索性项目的结果将缓解对PEG免疫原性的担忧， 组织工程或激励未来的研究策略，以减轻其影响。