Development of bio-integrated devices to enhance transplant survival for subcutaneous encapsulated cell therapies

微囊化细胞疗法(ECT)是涉及外壳的有吸引力的治疗平台 能够在聚合物中分泌治疗性蛋白的移植细胞集合 画框。这些技术代表着消除患者对复杂疾病的依赖的潜力 给药方案，同时将循环药物水平保持在健康、无毒的范围内 治疗范围从自身免疫性疾病到癌症。移植的 细胞通过封装材料从宿主免疫系统中分离出来，并是半透的， 多孔聚合物膜(免疫隔离膜)通过尺寸排斥效应。尽管 吸引了人们极大的兴趣，ECT设备还没有发现广泛的临床翻译 移植失败，移植细胞微环境中氧分压低， 纤维化是主要原因。与细胞堆积密度相关的尺寸考虑因素 代表着进一步的翻译挑战。这一挑战在皮下尤为尖锐。 (SC)植入，因为该地区的低血管化和高纤维性包膜的比率 队形。尽管有这些障碍，SC植入物已经引起了相当大的关注，因为 微创手术的要求和易于设备监控和 取回。在这项提案中，我将使用微细制造和生物电子器件方面的方法 改善SC-ECT移植细胞微环境内氧分压的设计 设备。在目标1中，我将开发先进的多物理模型来预测和解决氧气问题 需要植入的SC设备。在目标2中，我将使用表面化学修饰来抑制 生氧生物电子CT中的纤维化和确保移植物的长期存活 植入物。在目标3中，我将使用灵活的设计原则进行系统级集成 生物电子学、生物传感器发展与谐振式感应无线电能传输 接近了。如果成功，所产生的平台技术将支持SC移植细胞 长期存活，具有跨细胞类型和疾病模型的潜在应用。这项工作是 高度跨学科，融合了材料科学、细胞疗法、药物输送和 电子/电气工程。如果成功，这项工作将创造一种平台技术 能够满足微创技术中一系列未得到满足的治疗需求 植入部位，以降低临床翻译风险。我的背景主要是体能方面的 科学：通过这一奖学金，我将与我的同事导师，教授们密切合作。丹尼尔 麻省理工学院的安德森和罗伯特·兰格开发的技能将使我能够在界面上工作 在工程学和生命科学之间，以临床翻译为重点。

Encapsulated cell therapies (ECT) are attractive therapeutic platforms that involve the housing of collections of transplanted cells capable of secreting therapeutic proteins within polymeric frames. These technologies represent the potential to eliminate patient dependence on complex drug-dosing regimens while maintaining circulating drug levels within healthy, nontoxic therapeutic ranges for diseases ranging from autoimmune disorders to cancer. Transplanted cells are isolated from host immune systems via encapsulation materials and semipermeable, porous polymeric membranes (immunisolation membranes) via size exclusion effects. Despite attracting significant interest, ECT devices have not found widespread clinical translation owing to transplant failure, with low oxygen tension within the transplanted cell microenvironment and fibrosis representing major causes. Size considerations related to cellular packing density represent a further translational challenge. This challenge is particularly acute in subcutaneous (SC) implants owing to the region’s low vascularization and high rates of fibrotic capsule formation. Despite these hurdles, SC implants have attracted considerable attention owing to the minimally invasive surgery requirements and potential for easy device monitoring and retrieval. In this proposal, I will use approaches in microfabrication and bioelectronic device design to improve oxygen tension within the transplanted cell microenvironment in SC-ECT devices. In Aim 1 I will develop advanced multiphysics models to predict and address oxygen need in implanted SC devices. In Aim 2, I will use surface chemical modifications to suppress fibrosis and ensure long-term transplant survival in oxygen-generating bioelectronic ECT implants. In Aim 3, I will pursue system level integration using design principles in flexible bioelectronics, biosensor development and resonant inductive wireless power transfer approaches. If successful, the resulting platform technology will support SC transplanted cell survival long term, with potential applications across cell types and disease models. The work is highly interdisciplinary, incorporating materials science, cell therapies, drug delivery and electronic/electrical engineering. If successful, the work will create a platform technology capable of addressing a wide range of unmet therapeutic needs in minimally invasive implantation sites to de-risk clinical translation. My background is primarily in the physical sciences: through this Fellowship, I will work closely with my co-mentors, Profs. Daniel Anderson and Robert Langer at MIT to develop skills that will allow me to work at the interface between engineering and the life sciences, with a focus on clinical translation.