去细胞化
小岛
移植
细胞外基质
脚手架
β细胞
细胞生物学
分泌物
聚合物囊泡
胶囊
材料科学
胰岛素
生物医学工程
医学
内科学
生物
植物
复合材料
共聚物
两亲性
聚合物
作者
Hailin Ma,Linong Ji,Huan Fang,Ya Su,Yueqi Lu,Yan Shu,Peng Liu,Bing Li,Yuen Yee Cheng,Yi Nie,Yiming Zhong,Kedong Song
出处
期刊:Biofabrication
[IOP Publishing]
日期:2024-09-10
标识
DOI:10.1088/1758-5090/ad7907
摘要
Abstract The transplantation of islet beta cells offers an alternative to heterotopic islet transplantation for treating type 1 diabetes mellitus (T1DM). However, the use of systemic immunosuppressive drugs in islet transplantation poses significant risks to the body. To address this issue, we constructed an encapsulated hybrid scaffold loaded with islet beta cells. This article focuses on the preparation of the encapsulated structure using 3D printing, which incorporates porcine pancreas decellularized extracellular matrix (dECM) to the core scaffold. The improved decellularization method successfully preserved a substantial proportion of protein (such as Collagen I and Laminins) architecture and glycosaminoglycans in the dECM hydrogel, while effectively removing most of the DNA. The inclusion of dECM enhanced the physical and chemical properties of the scaffold, resulting in a porosity of 83.62±1.09% and a tensile stress of 1.85±0.16 MPa. In teams of biological activity, dECM demonstrated enhanced proliferation, differentiation, and expression of transcription factors such as Ki67, PDX1, and NKX6.1, leading to improved insulin secretion function in MIN-6 pancreatic beta cells. In the glucose-stimulated insulin secretion (GSIS) experiment on day 21, the maximum insulin secretion from the encapsulated structure reached 1.96±0.08 mIU/mL, representing a 44% increase compared to the control group. Furthermore, conventional capsule scaffolds leaverage the compatibility of natural biomaterials with macrophages to mitigate immune rejection. Here, incorporating curcumin into the capsule scaffold significantly reduced the secretion of pro-inflammatory cytokine (IL-1β, IL-6, TNF-α, IFN-γ) secretion by RAW264.7 macrophages and T cells in T1DM mice. This approach protected pancreatic islet cells against immune cell infiltration mediated by inflammatory factors and prevented insulitis. Overall, the encapsulated scaffold developed in this study shows promise as a natural platform for clinical treatment of T1DM.
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