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Nanostructured Non-Newtonian Drug Delivery Barrier Prevents Postoperative Intrapericardial Adhesions
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-06-17 , DOI: 10.1021/acsami.0c20084 Xichi Wang 1, 2, 3, 4 , Zongtao Liu 4 , Diego A Sandoval-Salaiza 1, 2, 3, 5 , Samson Afewerki 1, 2, 6 , Mildred G Jimenez-Rodriguez 1, 2, 3, 5 , Lorena Sanchez-Melgar 1, 2, 3, 5 , Gabriela Güemes-Aguilar 1, 2, 3, 7 , David G Gonzalez-Sanchez 1, 2, 3, 7 , Oscar Noble 1, 2, 3, 7 , Cecilia Lerma 1, 2, 3, 5 , Roberto Parra-Saldivar 1, 2, 5 , Dario R Lemos 1, 3 , Guillermo A Llamas-Esperon 8 , Jiawei Shi 4 , Li Li 3 , Anderson O Lobo 9 , Andres A Fuentes-Baldemar 1, 2, 3 , Joseph V Bonventre 1, 2, 3 , Nianguo Dong 4 , Guillermo U Ruiz-Esparza 1, 2, 3
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-06-17 , DOI: 10.1021/acsami.0c20084 Xichi Wang 1, 2, 3, 4 , Zongtao Liu 4 , Diego A Sandoval-Salaiza 1, 2, 3, 5 , Samson Afewerki 1, 2, 6 , Mildred G Jimenez-Rodriguez 1, 2, 3, 5 , Lorena Sanchez-Melgar 1, 2, 3, 5 , Gabriela Güemes-Aguilar 1, 2, 3, 7 , David G Gonzalez-Sanchez 1, 2, 3, 7 , Oscar Noble 1, 2, 3, 7 , Cecilia Lerma 1, 2, 3, 5 , Roberto Parra-Saldivar 1, 2, 5 , Dario R Lemos 1, 3 , Guillermo A Llamas-Esperon 8 , Jiawei Shi 4 , Li Li 3 , Anderson O Lobo 9 , Andres A Fuentes-Baldemar 1, 2, 3 , Joseph V Bonventre 1, 2, 3 , Nianguo Dong 4 , Guillermo U Ruiz-Esparza 1, 2, 3
Affiliation
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With the increasing volume of cardiovascular surgeries and the rising adoption rate of new methodologies that serve as a bridge to cardiac transplantation and that require multiple surgical interventions, the formation of postoperative intrapericardial adhesions has become a challenging problem that limits future surgical procedures, causes serious complications, and increases medical costs. To prevent this pathology, we developed a nanotechnology-based self-healing drug delivery hydrogel barrier composed of silicate nanodisks and polyethylene glycol with the ability to coat the epicardial surface of the heart without friction and locally deliver dexamethasone, an anti-inflammatory drug. After the fabrication of the hydrogel, mechanical characterization and responses to shear, strain, and recovery were analyzed, confirming its shear-thinning and self-healing properties. This behavior allowed its facile injection (5.75 ± 0.15 to 22.01 ± 0.95 N) and subsequent mechanical recovery. The encapsulation of dexamethasone within the hydrogel system was confirmed by 1H NMR, and controlled release for 5 days was observed. In vitro, limited cellular adhesion to the hydrogel surface was achieved, and its anti-inflammatory properties were confirmed, as downregulation of ICAM-1 and VCAM-1 was observed in TNF-α activated endothelial cells. In vivo, 1 week after administration of the hydrogel to a rabbit model of intrapericardial injury, superior efficacy was observed when compared to a commercial adhesion barrier, as histological and immunohistochemical examination revealed reduced adhesion formation and minimal immune infiltration of CD3+ lymphocytes and CD68+ macrophages, as well as NF-κβ downregulation. We presented a novel nanostructured drug delivery hydrogel system with unique mechanical and biological properties that act synergistically to prevent cellular infiltration while providing local immunomodulation to protect the intrapericardial space after a surgical intervention.
中文翻译：
纳米结构的非牛顿给药屏障可防止术后心包内粘连
随着心血管手术量的增加以及作为心脏移植桥梁和需要多次手术干预的新方法的采用率不断上升，术后心包内粘连的形成已成为一个具有挑战性的问题，限制了未来的手术程序，导致严重的并发症，并增加医疗费用。为了防止这种病理，我们开发了一种基于纳米技术的自愈合药物输送水凝胶屏障，由硅酸盐纳米盘和聚乙二醇组成，能够在没有摩擦的情况下覆盖心脏的心外膜表面，并局部输送抗炎药物地塞米松。在制造水凝胶后，分析了机械特性以及对剪切、应变和恢复的响应，确认其剪切稀化和自愈特性。这种行为使其易于注入（5.75 ± 0.15 至 22.01 ± 0.95 N）和随后的机械恢复。地塞米松在水凝胶系统中的包封通过1 H NMR，观察到控释5天。在体外，由于在 TNF-α 激活的内皮细胞中观察到 ICAM-1 和 VCAM-1 的下调，因此实现了对水凝胶表面的有限细胞粘附，并证实了其抗炎特性。体内, 将水凝胶给予兔心包内损伤模型 1 周后，与商业粘连屏障相比，观察到了优越的疗效，因为组织学和免疫组织化学检查显示 CD3+ 淋巴细胞和 CD68+ 巨噬细胞的粘连形成减少和免疫浸润最小，以及作为 NF-κβ 下调。我们提出了一种新型纳米结构药物输送水凝胶系统，具有独特的机械和生物学特性，可协同作用以防止细胞浸润，同时提供局部免疫调节以保护外科手术后的心包空间。
更新日期：2021-06-30
中文翻译：
纳米结构的非牛顿给药屏障可防止术后心包内粘连
随着心血管手术量的增加以及作为心脏移植桥梁和需要多次手术干预的新方法的采用率不断上升，术后心包内粘连的形成已成为一个具有挑战性的问题，限制了未来的手术程序，导致严重的并发症，并增加医疗费用。为了防止这种病理，我们开发了一种基于纳米技术的自愈合药物输送水凝胶屏障，由硅酸盐纳米盘和聚乙二醇组成，能够在没有摩擦的情况下覆盖心脏的心外膜表面，并局部输送抗炎药物地塞米松。在制造水凝胶后，分析了机械特性以及对剪切、应变和恢复的响应，确认其剪切稀化和自愈特性。这种行为使其易于注入（5.75 ± 0.15 至 22.01 ± 0.95 N）和随后的机械恢复。地塞米松在水凝胶系统中的包封通过1 H NMR，观察到控释5天。在体外，由于在 TNF-α 激活的内皮细胞中观察到 ICAM-1 和 VCAM-1 的下调，因此实现了对水凝胶表面的有限细胞粘附，并证实了其抗炎特性。体内, 将水凝胶给予兔心包内损伤模型 1 周后，与商业粘连屏障相比，观察到了优越的疗效，因为组织学和免疫组织化学检查显示 CD3+ 淋巴细胞和 CD68+ 巨噬细胞的粘连形成减少和免疫浸润最小，以及作为 NF-κβ 下调。我们提出了一种新型纳米结构药物输送水凝胶系统，具有独特的机械和生物学特性，可协同作用以防止细胞浸润，同时提供局部免疫调节以保护外科手术后的心包空间。
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