Elango Jeevithan, Zamora-Ledezma Camilo, Alexis Frank, Wu Wenhui, Maté-Sánchez de Val José Eduardo
Department of Biomaterials Engineering, Faculty of Health Sciences, UCAM-Universidad Católica San Antonio de Murcia, Campus de los Jerónimos 135, Guadalupe, 30107 Murcia, Spain.
Center of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India.
Pharmaceutics. 2023 Jun 28;15(7):1843. doi: 10.3390/pharmaceutics15071843.
Several approaches have evolved to facilitate the exploration of hydrogel systems in biomedical research. In this sense, poly(vinyl alcohol) (PVA) has been widely used in hydrogel (HG) fabrication for several therapeutic applications. The biological properties of PVA hydrogels (PVA-HGs) are highly dependent on their interaction with protein receptors and extracellular matrix (mainly calcium) deposition, for which there is not enough evidence from existing research yet. Thus, for the first time, the functional properties, like protein and mineral interactions, related to the proliferation of mesenchymal stem cells (MSCs) by silver nanoparticle (AgNP)-loaded PVA hydrogels (AgNPs-PVA-HGs) were investigated in the present study. The UV absorption spectrum and TEM microscopic results showed a maximum absorbance of synthesized AgNPs at 409 nm, with an average particle size of 14.5 ± 2.5 nm, respectively. The functional properties, such as the calcium-binding and the protein adsorption of PVA-HG, were accelerated by incorporating AgNPs; however, the swelling properties of the HGs were reduced by AgNPs, which might be due to the masking of the free functional groups (hydroxyl groups of PVA) by AgNPs. SEM images showed the presence of AgNPs with a more porous structure in the HGs. The proliferative effect of MSCs increased over culture time from day 1 to day 7, and the cell proliferative effect was upregulated by HGs with more pronounced AgNPs-PVA-HG. In addition, both HGs did not produce any significant cytotoxicity in the MSCs. The histological (bright light and H&E staining) and fluorescence microscopic images showed the presence of a cytoskeleton and the fibrillar structure of the MSCs, and the cells adhered more firmly to all HGs. More fibrillar bipolar and dense fibrillar structures were seen in the day 1 and day 7 cultures, respectively. Interestingly, the MSCs cultured on AgNPs-PVA-HG produced extracellular matrix deposition on day 7. Accordingly, the present results proved the biocompatibility of AgNPs-PVA-HG as a suitable system for culturing mammalian stem cells for regenerative tissue applications.
在生物医学研究中，已经出现了几种方法来促进水凝胶系统的探索。从这个意义上说，聚乙烯醇（PVA）已广泛用于水凝胶（HG）制造，用于多种治疗应用。PVA水凝胶（PVA-HGs）的生物学特性高度依赖于它们与蛋白质受体的相互作用以及细胞外基质（主要是钙）的沉积，目前现有研究对此尚无足够证据。因此，本研究首次研究了负载银纳米颗粒（AgNP）的PVA水凝胶（AgNPs-PVA-HGs）与间充质干细胞（MSCs）增殖相关的功能特性，如蛋白质和矿物质相互作用。紫外吸收光谱和透射电镜微观结果显示，合成的AgNPs在409 nm处有最大吸光度，平均粒径分别为14.5±2.5 nm。通过掺入AgNPs，PVA-HG的钙结合和蛋白质吸附等功能特性得到加速；然而，AgNPs降低了水凝胶的溶胀特性，这可能是由于AgNPs掩盖了游离官能团（PVA的羟基）。扫描电镜图像显示水凝胶中存在具有更多多孔结构的AgNPs。从第1天到第7天，MSCs的增殖效应随培养时间增加，具有更明显AgNPs-PVA-HG的水凝胶上调了细胞增殖效应。此外，两种水凝胶在MSCs中均未产生任何显著的细胞毒性。组织学（明视野和苏木精-伊红染色）和荧光显微镜图像显示了MSCs的细胞骨架和纤维状结构，并且细胞更牢固地粘附于所有水凝胶。在第1天和第7天的培养物中分别观察到更多的纤维状双极结构和致密的纤维状结构。有趣的是，在AgNPs-PVA-HG上培养的MSCs在第7天产生了细胞外基质沉积。因此，本研究结果证明了AgNPs-PVA-HG作为用于再生组织应用的培养哺乳动物干细胞的合适系统的生物相容性。
