School of Chemical Engineering, University of Birmingham, Birmingham, UK.
J Biomed Mater Res A. 2022 Jul;110(7):1401-1415. doi: 10.1002/jbm.a.37381. Epub 2022 Mar 8.
Corneal transplantation is the current gold standard treatment to restore visual acuity to patients with severe corneal diseases and injuries. Due to severe donor tissue shortage, efforts to develop a corneal equivalent have been made but the challenge remains unmet. Another issue of concern in ocular surgery is the difficult instillation and fast drainage of antibiotic ocular eye drops as bacterial infections can jeopardize implant success by delaying or impairing tissue healing. In this study, we developed antimicrobial silk-based hydrogels that have the potential to be photoactivated in situ, fully adapting to the corneal injury shape. Gentamicin-loaded methacrylated-silk (SilkMA) hydrogels were prepared within minutes using low UV intensity (3 mW/cm ). SilkMA gels provided a Young's modulus between 21 and 79 kPa together with a light transmittance spectrum and water content (83%-90%) similar to the human cornea. Polymer concentration (15%-25%) was found to offer a tool for tailoring the physical properties of the hydrogels. We confirmed that the methacrylation did not affect the material's in vitro degradation and biocompatibility by observing fibroblast adhesion and proliferation. Importantly, agar diffusion tests showed that the synthesized hydrogels were able to inhibit Staphylococcus aureus and Pseudomonas aeruginosa growth for 72 h. These characteristics along with their injectability and viscoelasticity demonstrate the potential of SilkMA hydrogels to be applied in several soft tissue engineering fields. As such, for the first time we demonstrate the potential of photocurable antimicrobial SilkMA hydrogels as a novel biomaterial to facilitate corneal regeneration.
角膜移植是目前恢复严重角膜疾病和损伤患者视力的金标准治疗方法。由于严重的供体组织短缺,人们一直在努力开发角膜等效物,但这一挑战仍未得到满足。眼外科的另一个问题是抗生素眼药水的滴注困难和快速排出,因为细菌感染会通过延迟或损害组织愈合而危及植入物的成功。在这项研究中,我们开发了具有潜在原位光激活能力的抗菌丝基水凝胶,可以完全适应角膜损伤形状。使用低紫外强度(3 mW/cm )在数分钟内制备了载庆大霉素的丝素甲基丙烯酰(SilkMA)水凝胶。SilkMA 凝胶的杨氏模量在 21 至 79 kPa 之间,透光率和含水量(83%-90%)与人类角膜相似。聚合物浓度(15%-25%)可用于调整水凝胶的物理性质。通过观察成纤维细胞的黏附和增殖,我们证实甲基丙烯酰化不会影响材料的体外降解和生物相容性。重要的是,琼脂扩散试验表明,合成的水凝胶能够抑制金黄色葡萄球菌和铜绿假单胞菌生长 72 小时。这些特性以及其可注射性和粘弹性表明 SilkMA 水凝胶在几个软组织工程领域具有应用潜力。因此,我们首次证明了光固化抗菌 SilkMA 水凝胶作为促进角膜再生的新型生物材料的潜力。