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具有高体内生物相容性和稳定性的海藻酸盐@TiO 杂化微胶囊用于细胞治疗。

Alginate@TiO hybrid microcapsules with high in vivo biocompatibility and stability for cell therapy.

机构信息

Laboratory of Inorganic Materials Chemistry (CMI), University of Namur, 61 Rue de Bruxelles, B-5000, Namur, Belgium; Namur Institute of Structured Matter (NISM), University of Namur, 61 Rue de Bruxelles, B-5000, Namur, Belgium.

Molecular Physiology Research Unit (URPhyM), Namur Research Institute for Life Sciences (NARILIS), University of Namur, 61 Rue de Bruxelles, B-5000, Namur, Belgium.

出版信息

Colloids Surf B Biointerfaces. 2021 Jul;203:111770. doi: 10.1016/j.colsurfb.2021.111770. Epub 2021 Apr 16.

DOI:10.1016/j.colsurfb.2021.111770
PMID:33894650
Abstract

Designing new materials to encapsulate living therapeutic cells for the treatment of the diseases caused by protein or hormone deficiencies is a great challenge. The desired materials need to be biocompatible towards both entrapped cells and host organisms, have long-term in vivo stability after implantation, allow the diffusion of nutrients and metabolites, and ensure perfect immune-isolation. The current work investigates the in vivo biocompatibility and stability of alginate@TiO hybrid microcapsules and the immune-isolation of entrapped HepG2 cells, to assess their potential for cell therapy. A comparison was made with alginate-silica hybrid microcapsules (ASA). These two hybrid microcapsules are implanted subcutaneously in female Wistar rats. The inflammatory responses of the rats are monitored by the histological examination of the implants and the surrounding tissues, to indicate their in vivo biocompatibility towards the hosts. The in vivo stability of the microcapsules is evaluated by the recovery rate of the intact microcapsules after implantation. The immune-isolation of the entrapped cells is assessed by their morphology, membrane integrity and intracellular enzymatic activity. The results show high viability of the entrapped cells and insignificant inflammation of the hosts, suggesting the excellent biocompatibility of alginate@TiO and ASA microcapsules towards both host organisms and entrapped cells. Compared to the ASA microcapsules, more intact alginate@TiO hybrid microcapsules are recovered 2-day and 2-month post-implantation and more cells remain alive, proving their better in vivo biocompability, stability, and immune-isolation. The present study demonstrates that the alginate@TiO hybrid microcapsule is a highly promising implantation material for cell therapy.

摘要

设计新的材料来封装用于治疗由蛋白质或激素缺乏引起的疾病的治疗细胞是一个巨大的挑战。期望的材料需要对包封的细胞和宿主生物体都具有生物相容性,在植入后具有长期的体内稳定性,允许营养物质和代谢物的扩散,并确保完美的免疫隔离。本工作研究了海藻酸盐@TiO2 杂化微胶囊的体内生物相容性和稳定性以及包封的 HepG2 细胞的免疫隔离,以评估它们用于细胞治疗的潜力。与海藻酸盐-二氧化硅杂化微胶囊(ASA)进行了比较。这两种杂化微胶囊被皮下植入雌性 Wistar 大鼠体内。通过对植入物和周围组织的组织学检查来监测大鼠的炎症反应,以指示其对宿主的体内生物相容性。通过植入后完整微胶囊的回收率来评估微胶囊的体内稳定性。通过包封细胞的形态、膜完整性和细胞内酶活性来评估其免疫隔离性能。结果表明,包封细胞具有高活力,宿主炎症不明显,表明海藻酸盐@TiO 和 ASA 微胶囊对宿主生物体和包封细胞均具有优异的生物相容性。与 ASA 微胶囊相比,在植入后 2 天和 2 个月时,更多的完整海藻酸盐@TiO2 杂化微胶囊被回收,更多的细胞仍然存活,证明其具有更好的体内生物相容性、稳定性和免疫隔离性。本研究表明,海藻酸盐@TiO2 杂化微胶囊是一种很有前途的细胞治疗植入材料。

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