Zwitterionic PEG-PC Hydrogels Modulate the Foreign Body Response in a Modulus-Dependent Manner.

Zwitterionic PEG-PC Hydrogels Modulate the Foreign Body Response in a Modulus-Dependent Manner.
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DOI:
10.1021/acs.biomac.8b00444
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发表时间:
2018-07-09
期刊:
影响因子:
6.2
通讯作者:
Peyton SR
Peyton SR
中科院分区:
化学2区
文献类型:
--
作者:
Jansen LE;Amer LD;Chen EY;Nguyen TV;Saleh LS;Emrick T;Liu WF;Bryant SJ;Peyton SR

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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)水凝胶由于其低成本、易用性以及通过分子量和交联密度调节其顺应性的能力而越来越受欢迎。PEG水凝胶可以在体内引发慢性炎症,但最近的证据表明,极端亲水性的两性离子材料和颗粒可以逃避免疫系统。为了将PEG基水凝胶的优点与两性离子的亲水性联合收割机结合起来,我们合成了以PEG和两性离子磷酰胆碱(PC)为共聚单体的水凝胶。最近的证据表明,刚性水凝胶引起增加的免疫细胞粘附到水凝胶,我们试图通过增加水凝胶的亲水性来减少。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起我们观察到的最高FBR。降低水凝胶模量(165 kPa至3 kPa)或PC含量(20重量%至0重量%)减轻了这种影响。在与高FBR相关的植入物表面发现了高密度的巨噬细胞,并且吸附到这些凝胶的蛋白质的质谱分析涉及细胞外基质、免疫应答和细胞粘附蛋白类别作为巨噬细胞募集到这些水凝胶的驱动因素。总体而言,我们表明,模量调节巨噬细胞粘附到两性离子-PEG水凝胶,并证明,水凝胶的化学修饰应与其物理性质并行研究,以优化植入物设计。
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 crosslinking 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 co-monomers 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 co-monomer elicited the highest FBR we observed. Lowering the hydrogel modulus (165 kPa to 3 kPa), or PC content (20 wt% 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 to these hydrogels. 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.
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