Laboratory of Electrostatic Methods of Bioencapsulation, Department of Biomaterials and Biotechnological Systems, Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Trojdena 4, 02-109 Warsaw, Poland.
Biomater Sci. 2020 Mar 17;8(6):1536-1574. doi: 10.1039/c9bm01337g.
Polymer microcarriers are being extensively explored as cell delivery vehicles in cell-based therapies and hybrid tissue and organ engineering. Spherical microcarriers are of particular interest due to easy fabrication and injectability. They include microbeads, composed of a porous matrix, and microcapsules, where matrix core is additionally covered with a semipermeable membrane. Microcarriers provide cell containment at implantation site and protect the cells from host immunoresponse, degradation and shear stress. Immobilized cells may be genetically altered to release a specific therapeutic product directly at the target site, eliminating side effects of systemic therapies. Cell microcarriers need to fulfil a number of extremely high standards regarding their biocompatibility, cytocompatibility, immunoisolating capacity, transport, mechanical and chemical properties. To obtain cell microcarriers of specified parameters, a wide variety of polymers, both natural and synthetic, and immobilization methods can be applied. Yet so far, only a few approaches based on cell-laden microcarriers have reached clinical trials. The main issue that still impedes progress of these systems towards clinical application is limited cell survival in vivo. Herein, we review polymer biomaterials and methods used for fabrication of cell microcarriers for in vivo biomedical applications. We describe their key limitations and modifications aiming at improvement of microcarrier in vivo performance. We also present the main applications of polymer cell microcarriers in regenerative medicine, pancreatic islet and hepatocyte transplantation and in the treatment of cancer. Lastly, we outline the main challenges in cell microimmobilization for biomedical purposes, the strategies to overcome these issues and potential future improvements in this area.
聚合物微载体作为细胞输送载体在基于细胞的治疗和混合组织与器官工程中得到了广泛的探索。由于易于制造和可注射性，球形微载体尤其受到关注。它们包括由多孔基质组成的微珠和其中基质核心被半透膜进一步覆盖的微胶囊。微载体在植入部位提供细胞容纳，并保护细胞免受宿主免疫反应、降解和剪切力的影响。固定化细胞可以进行基因改造，以便直接在靶部位释放特定的治疗产品，从而消除全身治疗的副作用。细胞微载体需要满足一系列关于其生物相容性、细胞相容性、免疫隔离能力、运输、机械和化学性质的极高标准。为了获得具有特定参数的细胞微载体，可以应用各种天然和合成聚合物以及固定化方法。然而，迄今为止，只有少数基于载细胞微载体的方法已经进入临床试验。仍然阻碍这些系统向临床应用发展的主要问题是体内细胞存活率有限。在此，我们综述了用于体内生物医学应用的细胞微载体的聚合物生物材料和制造方法。我们描述了它们的关键局限性和改进措施，旨在提高微载体的体内性能。我们还介绍了聚合物细胞微载体在再生医学、胰岛和肝细胞移植以及癌症治疗中的主要应用。最后，我们概述了细胞微固定化用于生物医学目的的主要挑战、克服这些问题的策略以及该领域的潜在未来改进。
