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

项目总结 聚乙二醇基水凝胶是一种具有广泛应用前景的蛋白质传输材料 以及骨组织工程的细胞疗法。然而，对聚乙二醇免疫原性的担忧 近年来出现了这种病毒，据估计，多达25%的人口具有抗体 由于通过药品、化妆品和其他含有聚乙二醇的产品而暴露于聚乙二醇，从而对抗聚乙二醇。而当 已发现抗聚乙二醇化反应会降低静脉注射聚乙二醇化药物的疗效，其 聚乙二醇水凝胶对再生疗法疗效的影响以前从未 研究过的，未知的。该项目的目标是通过在体内解决这一知识鸿沟 对免疫幼稚条件下产生抗聚乙二醇反应的动物进行比较的实验 控制。目的1包括一项小鼠皮下植入研究，该研究将阐明丹参的作用。 抗聚乙二醇免疫反应对聚乙二醇水凝胶的基本生物反应。《目标2》涉及一根骨头 组织工程学研究中，反聚乙二醇反应对水凝胶介导骨的传递的影响 形态发生蛋白-2(BMP-2)将在小鼠颅骨缺损模型中进行测试。定量测量 骨愈合与对照组动物相比，将被用来确定骨愈合是否为负面 受影响。这一探索性项目的结果将缓解人们对聚乙二醇免疫原性的担忧 组织工程或推动未来研究减轻其影响的策略。

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.