Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, NC, USA.
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, NC, USA; Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Acta Biomater. 2019 Sep 1;95:328-336. doi: 10.1016/j.actbio.2019.04.001. Epub 2019 Apr 3.
We have developed a biomimetic renal vascular scaffold based on a vascular corrosion casting technique. This study evaluated the feasibility of using this novel biomimetic scaffold for kidney regeneration in a rat kidney cortical defect model. Vascular corrosion casts were prepared from normal rat kidneys by perfusion with 10% polycaprolactone (PCL) solution, followed by tissue digestion. The corrosion PCL cast was coated with collagen, and PCL was removed from within the collagen coating, leaving only a hollow collagen-based biomimetic vascular scaffold. The fabricated scaffolds were pre-vascularized with MS1 endothelial cell coating, incorporated into 3D renal constructs, and subsequently implanted either with or without human renal cells in the renal cortex of nude rats. The implanted collagen-based vascular scaffold was easily identified and integrated into native kidney tissue. The biomimetic vascular scaffold coated with endothelial cells (MS1) showed significantly enhanced vascularization, as compared to the uncoated scaffold and hydrogel only groups (P < 0.001). Along with the improved vascularization effects, the MS1-coated scaffolds showed a significant renal cell infiltration from the neighboring host tissue, as compared to the other groups (P < 0.05). Moreover, addition of human renal cells to the MS1-coated scaffold resulted in further enhancement of vascularization and tubular structure regeneration within the implanted constructs. The biomimetic collagen vascular scaffolds coated with endothelial cells are able to enhance vascularization and facilitate the formation of renal tubules after 14 days when combined with human renal cells. This study shows the feasibility of bioengineering vascularized functional renal tissues for kidney regeneration. STATEMENT OF SIGNIFICANCE: Vascularization is one of the major hurdles affecting the survival and integration of implanted three-dimensional tissue constructs in vivo. A novel, biomimetic, collagen-based vascular scaffold that is structurally identical to native kidney tissue was developed and tested. This biomimetic vascularized scaffold system facilitates the development of new vessels and renal cell viability in vivo when implanted in a partial renal defect. The use of this scaffold system could address the challenges associated with vascularization, and may be an ideal treatment strategy for partial augmentation of renal function in patients with chronic kidney disease.
我们基于血管腐蚀铸造技术开发了一种仿生肾血管支架。本研究评估了在大鼠肾皮质缺损模型中使用这种新型仿生支架进行肾脏再生的可行性。通过灌注 10%的聚己内酯（PCL）溶液，然后进行组织消化，从正常大鼠肾脏中制备血管腐蚀铸型。腐蚀的 PCL 铸型用胶原蛋白包被，然后从胶原蛋白包被内去除 PCL，只留下一个空心的基于胶原蛋白的仿生血管支架。制造的支架先用 MS1 内皮细胞涂层进行预血管化，然后整合到 3D 肾构建体中，随后在裸鼠肾皮质中植入或不植入人肾细胞。植入的基于胶原蛋白的血管支架很容易被识别并整合到天然肾组织中。与未涂层支架和水凝胶组相比，涂覆内皮细胞（MS1）的仿生血管支架显示出明显增强的血管化（P<0.001）。除了改善血管化效果外，与其他组相比，MS1 涂层支架显示出明显的肾细胞从相邻宿主组织浸润（P<0.05）。此外，向 MS1 涂层支架中添加人肾细胞可进一步增强植入构建体中的血管化和管状结构再生。涂覆内皮细胞的仿生胶原蛋白血管支架在与人类肾细胞结合后 14 天内能够增强血管化并促进肾小管结构的再生。这项研究表明，生物工程化血管化功能性肾组织用于肾脏再生是可行的。
血管化是影响植入的三维组织构建体在体内存活和整合的主要障碍之一。开发并测试了一种新型的、仿生的、基于胶原蛋白的血管支架，其结构与天然肾组织相同。当植入部分肾缺损时，这种仿生血管化支架系统有助于体内新血管的形成和肾细胞的存活。这种支架系统的使用可以解决血管化相关的挑战，并且可能是治疗慢性肾脏病患者部分肾功能增强的理想治疗策略。
