Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Faculty of Pharmacy and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Departamento de Microbiología y Parasitología, Facultad de Biología, CIBUS, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Int J Pharm. 2022 Jan 25;612:121362. doi: 10.1016/j.ijpharm.2021.121362. Epub 2021 Dec 9.
The access of biodegradable scaffolds to the clinical arena is constrained by the absence of a suitable sterilization technique for the processing of advanced polymeric materials. Sterilization with supercritical CO (scCO) may circumvent some technological limitations (e.g., low temperature, no chemical residues on the material), although scCO can plasticize the polymer depending on the processing conditions used. In this latter case, the integration of the manufacturing and sterilization processes is of particular interest to obtain sterile and customized scaffolds in a single step. In this work, scCO was exploited as a concomitantly foaming and sterilizing agent for the first time, developing a one-step process for the production of vancomycin-loaded poly(ε-caprolactone) (PCL) bone scaffolds. The effect of the CO contact time on the sterility levels of the procedure was investigated, and the sterilization efficiency was evaluated against dry spores (Bacillus stearothermophilus, Bacillus pumilus and Bacillus atrophaeus). Vancomycin-loaded PCL scaffolds had relevant sustained release profiles for the prophylaxis of infections at the grafted area, even those caused by methicillin-resistant Staphylococcus aureus (MRSA). The biological performance of the scaffolds was evaluated in vitro regarding human mesenchymal stem cells (hMSCs) attachment and growth. Finally, the biocompatibility and angiogenic response of the manufactured sterile scaffolds was assessed in ovo through chick chorioallantoic membrane (CAM) assays.
可生物降解支架进入临床领域受到限制，因为缺乏适用于先进聚合物材料加工的消毒技术。超临界 CO（scCO）消毒可以规避一些技术限制（例如，低温，材料上无化学残留物），尽管 scCO 可能会根据使用的加工条件使聚合物增塑。在后一种情况下，将制造和消毒过程集成在一起，以在单个步骤中获得无菌和定制的支架尤为重要。在这项工作中，scCO 首次被用作同时发泡和消毒剂，首次开发了一步法生产载万古霉素的聚（ε-己内酯）（PCL）骨支架。研究了 CO 接触时间对该方法无菌水平的影响，并针对干孢子（嗜热脂肪芽孢杆菌，短小芽孢杆菌和萎缩芽孢杆菌）评估了消毒效率。载万古霉素的 PCL 支架具有相关的缓释特性，可预防移植物部位的感染，甚至是耐甲氧西林金黄色葡萄球菌（MRSA）引起的感染。体外评估了支架对人骨髓间充质干细胞（hMSC）附着和生长的生物学性能。最后，通过鸡胚绒毛尿囊膜（CAM）试验评估了制造的无菌支架的生物相容性和血管生成反应。
