Effect of alginate matrix engineered to mimic the pancreatic microenvironment on encapsulated islet function,Biotechnology and Bioengineering

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Effect of alginate matrix engineered to mimic the pancreatic microenvironment on encapsulated islet function
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2020-12-03 , DOI: 10.1002/bit.27641
Kevin Enck _{1,

2} , Riccardo Tamburrini _{2,

3} , Chaimov Deborah _{2,

3} , Carlo Gazia _{2,

3} , Alec Jost ₄ , Fatma Khalil ₂ , Abdelrahman Alwan ₂ , Giuseppe Orlando _{2,

3} , Emmanuel C Opara _{1,

2}

Affiliation

Islet transplantation is emerging as a therapeutic option for type 1 diabetes, albeit, only a small number of patients meeting very stringent criteria are eligible for the treatment because of the side effects of the necessary immunosuppressive therapy and the relatively short time frame of normoglycemia that most patients achieve. The challenge of the immune‐suppressive regimen can be overcome through microencapsulation of the islets in a perm‐selective coating of alginate microbeads with poly‐l‐lysine or poly‐ l‐ornithine. In addition to other issues including the nutrient supply challenge of encapsulated islets a critical requirement for these cells has emerged as the need to engineer the microenvironment of the encapsulation matrix to mimic that of the native pancreatic scaffold that houses islet cells. That microenvironment includes biological and mechanical cues that support the viability and function of the cells. In this study, the alginate hydrogel was modified to mimic the pancreatic microenvironment by incorporation of extracellular matrix (ECM). Mechanical and biological changes in the encapsulating alginate matrix were made through stiffness modulation and incorporation of decellularized ECM, respectively. Islets were then encapsulated in this new biomimetic hydrogel and their insulin production was measured after 7 days in vitro. We found that manipulation of the alginate hydrogel matrix to simulate both physical and biological cues for the encapsulated islets enhances the mechanical strength of the encapsulated islet constructs as well as their function. Our data suggest that these modifications have the potential to improve the success rate of encapsulated islet transplantation.

中文翻译：

模拟胰腺微环境的藻酸盐基质对封装胰岛功能的影响

胰岛移植正在成为 1 型糖尿病的一种治疗选择，尽管由于必要的免疫抑制治疗的副作用和相对较短的正常血糖时间框架，大多数患者只有少数符合非常严格标准的患者有资格接受治疗。患者达到。免疫抑制方案的挑战可以通过用聚赖氨酸或聚赖氨酸在藻酸盐微珠的选择性渗透涂层中微胶囊化来克服。-鸟氨酸。除了包括封装胰岛的营养供应挑战在内的其他问题外，对这些细胞的一项关键要求已经出现，因为需要设计封装基质的微环境以模拟容纳胰岛细胞的天然胰腺支架的微环境。该微环境包括支持细胞活力和功能的生物和机械线索。在这项研究中，通过掺入细胞外基质 (ECM) 对藻酸盐水凝胶进行修饰以模拟胰腺微环境。封装海藻酸盐基质的机械和生物变化分别通过刚度调制和脱细胞 ECM 的结合进行。然后将胰岛封装在这种新的仿生水凝胶中，并在体外 7 天后测量它们的胰岛素产量。我们发现，操纵藻酸盐水凝胶基质来模拟封装胰岛的物理和生物线索可增强封装胰岛结构的机械强度及其功能。我们的数据表明，这些修改有可能提高封装胰岛移植的成功率。

更新日期：2020-12-03

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