Department of Biomedical Engineering, College of Engineering, Peking University, Room 206, Fangzheng Building, 298 Chengfu Road, Haidian District, Beijing 100871, China.
Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, China.
Biomaterials. 2017 Sep;138:80-90. doi: 10.1016/j.biomaterials.2017.05.033. Epub 2017 May 22.
Ectopic transplantation of islets provides a beta cell-replacement approach that may allow the recovery of physiological regulation of the blood sugar level in patients with Type I diabetes (T1D). In development of new extrahepatic islet transplantation protocols in support of the islet engraftment, it is pivotal to develop scaffold materials with multifaceted functions to provide beneficial microenvironment, mediate host response in favor of vascularization/islet integration and maintain long-term islet function at the transplantation site. In this study, a new composite bilaminar decellularized scaffold (CDS) was fabricated with differential structural, degradation and mechanical properties by the combination of a fast-degrading porous collagen matrix and a mechanically supportive porcine pericardium. When investigated in the epididymal fat pad in syngeneic mouse models, it was shown that CDS could serve as superior scaffolds to promote islet adhesion and viability, and islet-CDS constructs also allowed rapid reversal of the hyperglycemic condition in the host. The engraftment and effects of islets were achieved at low islet numbers, accompanied by minimal adverse tissue reactions and optimal islet integration with the surrounding fat tissue. The bioactive surface, mechanical/chemical durability and biocompatibility of the CDS may all have played important roles in facilitating the engraftment of islets. Our study provided new insights into scaffold's function in the interplay of cells, materials and host tissue and the extracellular matrix-based scaffolds have potential for clinical translation in the beta cell-replacement therapy to treat T1D.
胰岛异位移植提供了一种β细胞替代方法，可能使 1 型糖尿病 (T1D) 患者的血糖水平恢复生理调节。在开发支持胰岛移植的新的肝外胰岛移植方案的过程中，开发具有多方面功能的支架材料以提供有益的微环境、调节有利于血管化/胰岛整合的宿主反应并维持移植部位的胰岛长期功能至关重要。在这项研究中，通过将快速降解的多孔胶原基质和机械支撑性猪心包结合在一起，制造了一种具有不同结构、降解和机械性能的新型双层脱细胞支架 (CDS)。当在同基因小鼠模型的附睾脂肪垫中进行研究时，结果表明 CDS 可以作为促进胰岛黏附和活力的优异支架，并且胰岛-CDS 构建体也允许宿主快速逆转高血糖状态。在低胰岛数量下实现了移植物的植入和作用，伴随着最小的不良组织反应和最佳的胰岛与周围脂肪组织的整合。CDS 的生物活性表面、机械/化学耐久性和生物相容性可能都在促进胰岛的植入中发挥了重要作用。我们的研究提供了关于支架在细胞、材料和宿主组织相互作用中的功能的新见解，基于细胞外基质的支架有可能在用于治疗 T1D 的β细胞替代治疗中进行临床转化。
