Department of Biomedical Engineering, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
J Biomed Mater Res A. 2011 Sep 15;98(4):544-53. doi: 10.1002/jbm.a.33147. Epub 2011 Jun 16.
Keratins are naturally derived proteins that can be fabricated into several biomaterial forms including hydrogels. These materials are a potential polymeric system for several tissue engineering and regenerative medicine applications due to their ability to support cell attachment, proliferation, and migration. However, little is known regarding their ability to support sustained release of therapeutic agents. This report describes the use of keratin hydrogels for sustained release of the antibiotic ciprofloxacin, which may prove useful to traumatic injury applications that would benefit from materials promoting tissue regeneration while also preventing acute infection. Hydrogels were formed from keratins obtained by oxidative extraction and known as keratose. We found that keratose hydrogels released ~60% of loaded ciprofloxacin over the first 10 days and that continued release was detectable over the course of 3 weeks. Released ciprofloxacin was bioactive, inhibiting growth of Staphylococcus aureus for 23 days in vitro and for 2 weeks in a mouse subcutaneous model. The rate of ciprofloxacin release was highly correlated with degradation of the keratin hydrogel and not consistent with simple diffusion. Further experiments indicated that ciprofloxacin binds to keratose through electrostatic interactions. These studies demonstrate the specific use of keratose hydrogels for the release of antibiotic and the potential for the more general use of this material in tissue engineering and regenerative medicine applications.
角蛋白是天然衍生的蛋白质，可以制成多种生物材料形式，包括水凝胶。由于其能够支持细胞附着、增殖和迁移，这些材料是几种组织工程和再生医学应用的潜在聚合物系统。然而，对于它们支持治疗剂持续释放的能力知之甚少。本报告描述了使用角蛋白水凝胶来持续释放抗生素环丙沙星，这对于可能受益于促进组织再生同时防止急性感染的材料的创伤性损伤应用可能是有用的。水凝胶是由氧化提取得到的角蛋白形成的，称为角蛋白。我们发现，角蛋白水凝胶在最初的 10 天内释放了约 60%的负载环丙沙星，并且在 3 周的过程中可以检测到持续释放。释放的环丙沙星具有生物活性，在体外抑制金黄色葡萄球菌生长 23 天，在小鼠皮下模型中抑制生长 2 周。环丙沙星的释放速率与角蛋白水凝胶的降解高度相关，而与简单扩散不一致。进一步的实验表明，环丙沙星通过静电相互作用与角蛋白结合。这些研究表明了角蛋白水凝胶在抗生素释放方面的特定用途，以及该材料在组织工程和再生医学应用中更广泛应用的潜力。
