Krishnan Siddharth R, Langer Robert, Anderson Daniel G
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA USA.
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA USA.
MRS Commun. 2025;15(1):21-33. doi: 10.1557/s43579-024-00678-6. Epub 2024 Dec 2.
Transplanted cells can act as living drug factories capable of secreting therapeutic proteins , with applications in the treatment of Type 1 diabetes (T1D), blood borne disease, vision disorders, and degenerative neural disease, potentially representing functional cures for chronic conditions. However, attack from the host immune system represents a major challenge, requiring chronic immunosuppression to enable long-lived cell transplantation . Encapsulating cells in engineered biomaterials capable of excluding components of the host immune system while allowing for the transport of therapeutic proteins, oxygen, nutrients, metabolites, and waste products represents a potential solution. However, the foreign-body response can lead to isolation from native vasculature and hypoxia leading to cell death. In this prospective article, we highlight materials-based solutions to three important challenges in the field: (i) improving biocompatibility and reducing fibrosis; (ii) enhancing transport of secreted protein drugs and key nutrients and oxygen engineered, semipermeable membranes; and (iii) improving oxygenation. These efforts draw on several disciplines in materials' research, including polymer science, surfaces, membranes, biomaterials' microfabrication, and flexible electronics. If successful, these efforts could lead to new therapies for chronic disease and are a rich space for both fundamental materials' discovery and applied translational science.
移植细胞可充当能够分泌治疗性蛋白质的活体药物工厂，在治疗1型糖尿病（T1D）、血液传播疾病、视力障碍和退行性神经疾病方面有应用，有可能为慢性病带来功能性治愈方法。然而，来自宿主免疫系统的攻击是一个重大挑战，需要长期免疫抑制才能实现长期的细胞移植。将细胞封装在能够排除宿主免疫系统成分同时允许治疗性蛋白质、氧气、营养物质、代谢产物和废物运输的工程生物材料中是一种潜在的解决方案。然而，异物反应会导致与天然脉管系统隔离并缺氧，从而导致细胞死亡。在这篇前瞻性文章中，我们重点介绍了基于材料的解决方案，以应对该领域的三个重要挑战：（i）提高生物相容性并减少纤维化；（ii）增强分泌蛋白药物以及关键营养物质和氧气通过工程化半透膜的运输；（iii）改善氧合作用。这些努力借鉴了材料研究中的多个学科，包括聚合物科学、表面科学、膜科学、生物材料微加工和柔性电子学。如果成功，这些努力可能会带来慢性病的新疗法，并且对于基础材料发现和应用转化科学来说都是一个丰富的领域。
