Douglass Megan, Hopkins Sean, Chug Manjyot Kaur, Kim Gina, Garren Mark Richard, Ashcraft Morgan, Nguyen Dieu Thao, Tayag Nicole, Handa Hitesh, Brisbois Elizabeth J
School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens, Georgia 30602, United States.
Office of Research, University Research Animal Resources, University of Georgia, Athens, Georgia 30602, United States.
ACS Appl Mater Interfaces. 2021 Nov 10;13(44):52425-52434. doi: 10.1021/acsami.1c18190. Epub 2021 Nov 1.
Foreign body response and infection are two universal complications that occur with indwelling medical devices. In response, researchers have developed different antimicrobial and antifouling surface strategies to minimize bacterial colonization and fibrous encapsulation. In this study, the nitric oxide (NO) donor -nitroso--acetylpenicillamine (SNAP) and silicone oil were impregnated into silicone rubber cannulas (SR-SNAP-Si) using a solvent swelling method to improve the antimicrobial properties and decrease the foreign body response. The fabricated SR-SNAP-Si cannulas demonstrated a stable, prolonged NO release, exhibited minimal SNAP leaching, and maintained sliding angles < 15° for 21 days. SR-SNAP-Si cannulas displayed enhanced antimicrobial efficacy against in a 7-day biofilm bioreactor study, reducing the viability of adhered bacteria by 99.2 ± 0.2% compared to unmodified cannulas while remaining noncytotoxic toward human fibroblast cells. Finally, SR-SNAP-Si cannulas were evaluated for the first time in a 14- and 21-day subcutaneous mouse model, showing significantly enhanced biocompatibility compared to control cannulas by reducing the thickness of fibrous encapsulation by 60.9 ± 6.1 and a 60.8 ± 10.5% reduction in cell density around the implant site after 3 weeks. Thus, this work demonstrates that antifouling, NO-releasing surfaces can improve the lifetime and safety of indwelling medical devices.
异物反应和感染是留置医疗设备普遍会出现的两种并发症。作为应对措施，研究人员开发了不同的抗菌和防污表面策略，以尽量减少细菌定植和纤维包裹。在本研究中，使用溶剂溶胀法将一氧化氮（NO）供体——亚硝基乙酰青霉胺（SNAP）和硅油浸渍到硅橡胶套管（SR-SNAP-Si）中，以提高抗菌性能并减少异物反应。制备的SR-SNAP-Si套管显示出稳定、持久的NO释放，SNAP浸出极少，并且在21天内保持滑动角<15°。在一项为期7天的生物膜生物反应器研究中，SR-SNAP-Si套管对[具体细菌名称未给出]显示出增强的抗菌效果，与未改性的套管相比，附着细菌的活力降低了99.2±0.2%，同时对人成纤维细胞仍无细胞毒性。最后，在14天和21天的皮下小鼠模型中首次对SR-SNAP-Si套管进行了评估，结果显示与对照套管相比，生物相容性显著提高，3周后纤维包裹厚度减少了60.9±6.1%，植入部位周围的细胞密度降低了60.8±10.5%。因此，这项工作表明，防污、释放NO的表面可以提高留置医疗设备的使用寿命和安全性。
