School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, MA 02138, USA. Wyss Institute for Biologically Inspired Engineering at Harvard, 3 Blackfan Circle, Boston, MA 02115, USA.
Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Department of Pediatric Cardiac Surgery, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40126 Bologna, Italy.
Sci Transl Med. 2015 Sep 23;7(306):306ra149. doi: 10.1126/scitranslmed.aaa2406.
A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinical translation. We developed a multifunctional, catheter-based technology with no implantable rigid components that functions by unfolding an adhesive-loaded elastic patch and deploying a double-balloon design to stabilize and apply pressure to the patch against the tissue defect site. The device uses a fiber-optic system and reflective metallic coating to uniformly disperse ultraviolet light for adhesive activation. Using this device, we demonstrate closure on the distal side of a defect in porcine abdominal wall, stomach, and heart tissue ex vivo. The catheter was further evaluated as a potential tool for tissue closure in vivo in rat heart and abdomen and as a perventricular tool for closure of a challenging cardiac septal defect in a large animal (porcine) model. Patches attached to the heart and abdominal wall with the device showed similar inflammatory response as sutures, with 100% small animal survival, indicating safety. In the large animal model, a ventricular septal defect in a beating heart was reduced to <1.6 mm. This new therapeutic platform has utility in a range of clinical scenarios that warrant minimally invasive and atraumatic repair of hard-to-reach defects.
先天性或医源性组织缺陷通常需要通过开放性手术或可侵蚀组织的金属部件来闭合。可生物降解的疏水性光激活胶粘剂是缝线的一种有吸引力的替代物，但缺乏专门设计的微创输送工具，这限制了它们的临床转化。我们开发了一种多功能的、基于导管的技术，没有可植入的刚性部件，它通过展开带有胶粘剂的弹性贴片并部署双球囊设计来稳定和对组织缺陷部位施加压力来起作用。该设备使用光纤系统和反射性金属涂层来均匀分散紫外线以激活胶粘剂。使用该设备，我们在猪的腹壁、胃和心脏组织的缺陷远端演示了闭合。该导管还进一步评估了作为在体内大鼠心脏和腹部组织闭合的潜在工具，以及作为大型动物（猪）模型中具有挑战性的心脏间隔缺损的经皮闭合工具的潜力。用该设备将贴片附着在心脏和腹壁上，其炎症反应与缝线相似，小型动物的存活率为 100%，表明其安全性。在大型动物模型中，跳动心脏中的室间隔缺损减少至 <1.6 毫米。这种新的治疗平台在多种临床情况下具有实用性，需要微创和无创伤地修复难以到达的缺陷。
