Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal.
Tissue Eng Part C Methods. 2022 Jul;28(7):325-334. doi: 10.1089/ten.TEC.2022.0029. Epub 2022 May 10.
Cell-based therapies require a large number of cells, as well as appropriate methods to deliver the cells to damaged tissue. Microcarriers provide an optimal platform for large-scale cell culture while also improving cell retention during cell delivery. However, this technology still presents significant challenges due to low-throughput fabrication methods and an inability of the microcarriers to recreate the properties of human tissue. This work proposes, for the first time, the use of methacryloyl platelet lysates (PLMA), a photocrosslinkable material derived from human platelet lysates, to produce porous microcarriers. Initially, high quantities of PLMA/alginate core-shell microcapsules are produced using coaxial electrospray. Subsequently, the microcapsules are collected, irradiated with ultraviolet light, washed, and freeze dried yielding PLMA microsponges. These microsponges are able to support the adhesion and proliferation of human adipose-derived stem cells, while also displaying potential in the assembly of autologous microtissues. Cell-laden microsponges were shown to self-organize into aggregates, suggesting possible applications in bottom-up tissue engineering applications. Impact Statement Microcarriers have increasingly been used as delivery platforms in cell therapy. Herein, the encapsulation of human-derived proteins in alginate microcapsules is proposed as a method to produce microcarriers from photopolymerizable materials. The capsules function as a template structure, which is then processed into spherical microparticles, which can be used in cell culture, cell delivery, and bottom-up assembly. As a proof of concept, this method was combined with lyophilization to process methacryloyl platelet lysates into injectable microsponges for cell delivery.
细胞疗法需要大量的细胞，以及将细胞递送到受损组织的适当方法。微载体为大规模细胞培养提供了一个理想的平台，同时在细胞递送过程中提高了细胞的保留率。然而，由于低通量的制造方法以及微载体无法重现人体组织的特性，这项技术仍然存在重大挑战。本研究首次提出使用甲基丙烯酰化血小板裂解物（PLMA），一种源自人血小板裂解物的光交联材料，来制备多孔微载体。最初，使用同轴静电喷雾法生产大量的 PLMA/藻酸盐核壳微胶囊。随后，收集微胶囊，用紫外线照射，洗涤，冷冻干燥得到 PLMA 微海绵。这些微海绵能够支持人脂肪来源干细胞的黏附和增殖，并且在自体微组织的组装中也显示出潜力。负载细胞的微海绵能够自组装成聚集体，表明在自下而上的组织工程应用中可能有应用。 研究意义 微载体已越来越多地被用作细胞治疗中的递送平台。本文提出将人源蛋白包封在藻酸盐微胶囊中，作为用光聚合材料制备微载体的方法。胶囊作为模板结构，然后加工成球形微粒，可用于细胞培养、细胞递送和自下而上的组装。作为概念验证，该方法与冻干法相结合，将甲基丙烯酰化血小板裂解物加工成用于细胞递送的可注射微海绵。
