Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, 250 Wuxing Street, Taipei 110, Taiwan.
International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, 250 Wuxing Street, Taipei 110, Taiwan.
ACS Biomater Sci Eng. 2023 Feb 13;9(2):719-731. doi: 10.1021/acsbiomaterials.2c00899. Epub 2023 Jan 3.
Cell therapy has significant therapeutic potential but is often limited by poor donor cell retention and viability at the host implantation site. Biomaterials can improve cell retention by providing cells with increased cell-cell and cell-matrix contacts and materials that allow three-dimensional cell culture to better recapitulate native cell morphology and function. In this study, we engineered a scaffold that allows for cell encapsulation and sustained three-dimensional cell culture. Since cell therapy is largely driven by paracrine secretions, the material was fabricated by electrospinning to have a large internal surface area, micrometer-thin walls, and nanoscale surface pores to allow for nutrient exchange without early cell permeation. The material is degradable, which allows for less invasive removal of the implant. Here, a biodegradable poly(lactic--glycolic acid) (PLGA) microtube array membrane was fabricated. testing showed that the material supported the culture of human dermal fibroblasts for at least 21 days, with paracrine secretion of pro-angiogenic FGF2. xenotransplantation of human cells in an immunocompetent mouse showed that donor cells could be maintained for more than one month and the material showed no obvious toxicity. Analysis of gene expression and tissue histology surrounding the implant showed that the material produced muted inflammatory and immune responses compared to a permanent implant and increased markers of angiogenesis.
细胞治疗具有显著的治疗潜力，但通常受到供体细胞在宿主植入部位的保留和活力差的限制。生物材料可以通过增加细胞-细胞和细胞-基质接触来提高细胞保留率，并且允许三维细胞培养更好地再现天然细胞形态和功能的材料。在这项研究中，我们设计了一种允许细胞包封和持续三维细胞培养的支架。由于细胞治疗在很大程度上受旁分泌分泌物的驱动，因此该材料通过静电纺丝制造，具有大的内表面积、微米级薄的壁和纳米级表面孔，允许营养物质交换而不会早期穿透细胞。该材料可降解，可减少植入物的侵入性去除。在这里，制造了一种可生物降解的聚（乳酸-羟基乙酸）（PLGA）微管阵列膜。 测试表明，该材料至少支持人真皮成纤维细胞培养 21 天，具有促血管生成 FGF2 的旁分泌分泌。 在免疫活性小鼠中进行的人细胞异种移植表明，供体细胞可以维持一个月以上，并且材料没有明显的毒性。对植入物周围的基因表达和组织组织学的分析表明，与永久性植入物相比，该材料产生的炎症和免疫反应减弱，并且增加了血管生成标志物。
