糖尿病是一种困扰全球4.63亿人的疾病。这些患者中约有4000万患有1型糖尿病(T1DM),全球发病率每年增加5%。T1DM是人体免疫系统攻击胰腺的地方,特别是胰腺β细胞,用抗体来阻止胰岛素的产生。虽然目前的治疗方法,如外源性胰岛素注射已经成功,高昂的胰岛素成本和细致的给药需要替代的长期解决方案来治疗糖尿病引起的血糖失调.封装胰岛移植(EIT)是糖尿病的组织工程解决方案。供体胰岛被封装在半透性水凝胶中,允许氧气扩散,葡萄糖,和胰岛素,但防止白细胞浸润和抗体进入移植细胞。虽然在小动物模型中很成功,由于必需的长期全身性免疫抑制剂和一致的免疫排斥,EIT仍远未商业化。大多数已发表的研究集中在定制胶囊材料的特征以促进临床生存能力。然而,大多数研究仅限于生化变化。目前对基质刚度对白细胞功能的影响的机械生物学研究,尤其是巨噬细胞-主要的异物反应协调器,在定制对组织工程疗法如EIT的有利反应方面显示出希望。在这次审查中,我们探索提高EIT临床可行性的策略。免疫系统的简要概述,异物反应,和当前的生化方法将在整个探索中阐明。此外,将提出使用基质刚度作为胶囊设计参数以增加EIT功效和临床可行性的论点。
Diabetes is a disease that plagues over 463 million people globally. Approximately 40 million of these patients have type 1 diabetes mellitus (T1DM), and the global incidence is increasing by up to 5% per year. T1DM is where the body\'s immune system attacks the pancreas, specifically the pancreatic beta cells, with antibodies to prevent insulin production. Although current treatments such as exogenous insulin injections have been successful, exorbitant insulin costs and meticulous administration present the need for alternative long-term solutions to glucose dysregulation caused by diabetes. Encapsulated islet transplantation (EIT) is a tissue-engineered solution to diabetes. Donor islets are encapsulated in a semipermeable hydrogel, allowing the diffusion of oxygen, glucose, and insulin but preventing leukocyte infiltration and antibody access to the transplanted cells. Although successful in small animal models, EIT is still far from commercial use owing to necessary long-term systemic immunosuppressants and consistent immune rejection. Most published research has focused on tailoring the characteristics of the capsule material to promote clinical viability. However, most studies have been limited in scope to biochemical changes. Current mechanobiology studies on the effect of substrate stiffness on the function of leukocytes, especially macrophages-primary foreign body response (FBR) orchestrators, show promise in tailoring a favorable response to tissue-engineered therapies such as EIT. In this review, we explore strategies to improve the clinical viability of EIT. A brief overview of the immune system, the FBR, and current biochemical approaches will be elucidated throughout this exploration. Furthermore, an argument for using substrate stiffness as a capsule design parameter to increase EIT efficacy and clinical viability will be posed.