Chen Jiaxi, Zhou Huiqun, Xie Daping, Niu Yiming
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Macau SAR, China.
Chin Med. 2021 Dec 4;16(1):131. doi: 10.1186/s13020-021-00526-y.
Implantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implants. The foreign-body reaction can be modulated by control of the material properties of the implants.
First, we synthesized methacrylated Bletilla striata Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and modulus were measured to characterize the properties of BSP cryogels. Live/dead staining of cells and CCK-8 were performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for the tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials.
Our data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels showed well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (Tnfa and Il1b) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure.
Collectively, our findings revealed Bletilla striata polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body reaction and promote the performance of medical devices.
生物材料的植入可能会引发宿主组织的异物反应，这决定了植入物整合的结果以及其生物学性能。异物反应可通过控制植入物的材料特性来调节。
首先，我们合成了甲基丙烯酸化白及多糖（BSP-MA），并通过对溶剂-前驱体系统进行冻融处理，利用该材料构建了一系列开放多孔的冷冻凝胶。其次，测量孔径和模量以表征BSP冷冻凝胶的特性。进行细胞活/死染色和CCK-8实验以测试支架的细胞相容性。此外，还进行了实时定量PCR实验。最后，将BSP支架皮下植入以验证宿主组织与材料之间的异物反应。
我们的数据表明，只需调整浓度就能制备出具有不同孔径和模量的冷冻凝胶。此外，冷冻凝胶在体外实验中显示出良好的细胞相容性，并且随着孔径的增加，促炎相关基因（Tnfa和Il1b）的表达水平上调。体内实验进一步证明，随着孔径的增加，更多的免疫细胞浸润到材料内部区域。通过调整材料微观结构可以调节异物反应和免疫调节细胞的分布。
总的来说，我们的研究结果表明，具有不同孔径的白及多糖冷冻凝胶支架可以在空间上控制异物反应。冷冻凝胶的微观结构可以不同程度地引导炎症细胞的分布，影响血管和纤维囊的形成，最终影响材料与组织的整合。这项工作展示了一种调节异物反应和提高医疗器械性能的实用策略。
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