在过去的几年里,来自脱细胞细胞外基质(dECM)的水凝胶用于再生医学目的的用途显着增加。固有的生物活性和免疫调节特性表明这些材料是用于治疗应用的有希望的候选物。然而,到目前为止,限制,如动物到动物的变异性仍然阻碍临床翻译。此外,组织来源的选择,脱细胞和增溶方案导致dECM衍生的水凝胶的差异。在这种情况下,详细的化学表征,应进行水凝胶的物理和生物学特性,关注这些特性如何受到动物间变异的影响。在这里,我们报告了来自牛心包(dBP)的脱细胞细胞外基质的水凝胶的详细表征。蛋白质含量,流变性能,可注射性,表面微观结构,体外稳定性和细胞相容性进行了评估,特别注意动物与动物之间的差异。凝胶化过程显示为热响应性,获得的dBP水凝胶是可注射的,多孔,在水性介质中稳定达2周,在酶环境中快速降解和细胞相容性,能够维持人间充质基质细胞的细胞活力。蛋白质组学分析的结果证明,dBP水凝胶的成分高度丰富,除了胶原蛋白等结构蛋白外,还保留生物活性蛋白聚糖和糖蛋白。关于化学成分,显示了动物间的变异性,但是生物学特性没有受到影响,在不同批次中保持一致。总之,这些结果表明dBP水凝胶是再生医学应用的优异候选物。
In the past years, the use of hydrogels derived from decellularized extracellular matrix (dECM) for regenerative medicine purposes has significantly increased. The intrinsic bioactive and immunomodulatory properties indicate these materials as promising candidates for therapeutical applications. However, to date, limitations such as animal-to-animal variability still hinder the clinical translation. Moreover, the choice of tissue source, decellularization and solubilization protocols leads to differences in dECM-derived hydrogels. In this context, detailed characterization of chemical, physical and biological properties of the hydrogels should be performed, with attention to how these properties can be affected by animal-to-animal variability. Herein, we report a detailed characterization of a hydrogel derived from the decellularized extracellular matrix of bovine pericardium (dBP). Protein content, rheological properties, injectability, surface microstructure, in vitro stability and cytocompatibility were evaluated, with particular attention to animal-to-animal variability. The gelation process showed to be thermoresponsive and the obtained dBP hydrogels are injectable, porous, stable up to 2 weeks in aqueous media, rapidly degrading in enzymatic environment and cytocompatible, able to maintain cell viability in human mesenchymal stromal cells. Results from proteomic analysis proved that dBP hydrogels are highly rich in composition, preserving bioactive proteoglycans and glycoproteins in addition to structural proteins such as collagen. With respect to the chemical composition, animal-to-animal variability was shown, but the biological properties were not affected, which remained consistent in different batches. Taken together these results show that dBP hydrogels are excellent candidates for regenerative medicine applications.