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Zwitterionic PEG-PC Hydrogels Modulate the Foreign Body Response in a Modulus-Dependent Manner
Biomacromolecules ( IF 6.2 ) Pub Date : 2018-04-26 00:00:00 , DOI: 10.1021/acs.biomac.8b00444 Lauren E Jansen , Luke D Amer 1 , Esther Y-T Chen 2 , Thuy V Nguyen , Leila S Saleh 1 , Todd Emrick , Wendy F Liu 2 , Stephanie J Bryant 1 , Shelly R Peyton
Biomacromolecules ( IF 6.2 ) Pub Date : 2018-04-26 00:00:00 , DOI: 10.1021/acs.biomac.8b00444 Lauren E Jansen , Luke D Amer 1 , Esther Y-T Chen 2 , Thuy V Nguyen , Leila S Saleh 1 , Todd Emrick , Wendy F Liu 2 , Stephanie J Bryant 1 , Shelly R Peyton
Affiliation
Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and cross-linking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with comonomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic comonomer elicited the highest FBR. Lowering the hydrogel modulus (165 to 3 kPa), or PC content (20 to 0 wt %), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design.
中文翻译:
两性离子 PEG-PC 水凝胶以模量依赖性方式调节异物反应
减少植入生物材料的异物反应(FBR)将提高其在组织工程中的性能。聚乙二醇 (PEG) 水凝胶因其成本低、易于使用以及能够通过分子量和交联密度调节其顺应性而在该应用中越来越受欢迎。PEG水凝胶可以在体内引发慢性炎症,但最近的证据表明,极其亲水的两性离子材料和颗粒可以逃避免疫系统。为了将基于 PEG 的水凝胶的优点与两性离子的亲水性结合起来,我们用共聚单体 PEG 和两性离子磷酸胆碱(PC)合成了水凝胶。最近的证据表明,坚硬的水凝胶会引起免疫细胞对水凝胶的粘附增加,我们试图通过增加水凝胶的亲水性来减少这种粘附。令人惊讶的是,具有最高量的两性离子共聚单体的水凝胶引发了最高的FBR。降低水凝胶模量(165 至 3 kPa)或 PC 含量(20 至 0 wt%)可以减轻这种影响。在植入物表面发现了与高 FBR 相关的高密度巨噬细胞,对吸附到这些凝胶上的蛋白质进行质谱分析表明,细胞外基质、免疫反应和细胞粘附蛋白类别是巨噬细胞募集的驱动因素。总体而言,我们表明模量调节巨噬细胞对两性离子-PEG水凝胶的粘附,并证明对水凝胶的化学修饰应与其物理特性同时研究,以优化植入物设计。
更新日期:2018-04-26
中文翻译:
两性离子 PEG-PC 水凝胶以模量依赖性方式调节异物反应
减少植入生物材料的异物反应(FBR)将提高其在组织工程中的性能。聚乙二醇 (PEG) 水凝胶因其成本低、易于使用以及能够通过分子量和交联密度调节其顺应性而在该应用中越来越受欢迎。PEG水凝胶可以在体内引发慢性炎症,但最近的证据表明,极其亲水的两性离子材料和颗粒可以逃避免疫系统。为了将基于 PEG 的水凝胶的优点与两性离子的亲水性结合起来,我们用共聚单体 PEG 和两性离子磷酸胆碱(PC)合成了水凝胶。最近的证据表明,坚硬的水凝胶会引起免疫细胞对水凝胶的粘附增加,我们试图通过增加水凝胶的亲水性来减少这种粘附。令人惊讶的是,具有最高量的两性离子共聚单体的水凝胶引发了最高的FBR。降低水凝胶模量(165 至 3 kPa)或 PC 含量(20 至 0 wt%)可以减轻这种影响。在植入物表面发现了与高 FBR 相关的高密度巨噬细胞,对吸附到这些凝胶上的蛋白质进行质谱分析表明,细胞外基质、免疫反应和细胞粘附蛋白类别是巨噬细胞募集的驱动因素。总体而言,我们表明模量调节巨噬细胞对两性离子-PEG水凝胶的粘附,并证明对水凝胶的化学修饰应与其物理特性同时研究,以优化植入物设计。