Moulisová Vladimíra, Poveda-Reyes Sara, Sanmartín-Masiá Esther, Quintanilla-Sierra Luis, Salmerón-Sánchez Manuel, Gallego Ferrer Gloria
Division of Biomedical Engineering, School of Engineering, University of Glasgow, Rankine Bld, Oakfield Avenue G12 8LT, Glasgow, U.K.
Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Camino de Vera s/n. 46022 Valencia, Spain.
ACS Omega. 2017 Nov 30;2(11):7609-7620. doi: 10.1021/acsomega.7b01303. Epub 2017 Nov 7.
Gelatin-hyaluronic acid (Gel-HA) hybrid hydrogels have been proposed as matrices for tissue engineering because of their ability to mimic the architecture of the extracellular matrix. Our aim was to explore whether tyramine conjugates of Gel and HA, producing injectable hydrogels, are able to induce a particular phenotype of encapsulated human mesenchymal stem cells without the need for growth factors. While pure Gel allowed good cell adhesion without remarkable differentiation and pure HA triggered chondrogenic differentiation without cell spreading, the hybrids, especially those rich in HA, promoted chondrogenic differentiation as well as cell proliferation and adhesion. Secretion of chondrogenic markers such as aggrecan, SOX-9, collagen type II, and glycosaminoglycans was observed, whereas osteogenic, myogenic, and adipogenic markers (RUNX2, sarcomeric myosin, and lipoproteinlipase, respectively) were not present after 2 weeks in the growth medium. The most promising matrix for chondrogenesis seems to be a mixture containing 70% HA and 30% Gel as it is the material with the best mechanical properties from all compositions tested here, and at the same time, it provides an environment suitable for balanced cell adhesion and chondrogenic differentiation. Thus, it represents a system that has a high potential to be used as the injectable material for cartilage regeneration therapies.
明胶-透明质酸（Gel-HA）杂化水凝胶因其能够模拟细胞外基质的结构而被提议作为组织工程的基质。我们的目的是探究Gel和HA的酪胺缀合物（可制备可注射水凝胶）是否能够在无需生长因子的情况下诱导被封装的人间充质干细胞产生特定表型。虽然纯Gel能使细胞良好黏附但无明显分化，纯HA能触发软骨生成分化但细胞不铺展，但杂化水凝胶，尤其是富含HA的杂化水凝胶，既能促进软骨生成分化，又能促进细胞增殖和黏附。观察到了软骨生成标志物如聚集蛋白聚糖、SOX-9、II型胶原蛋白和糖胺聚糖的分泌，而在生长培养基中培养2周后未检测到成骨、成肌和脂肪生成标志物（分别为RUNX2、肌节肌球蛋白和脂蛋白脂肪酶）。对于软骨生成而言，最有前景的基质似乎是含有70%HA和30%Gel的混合物，因为它是此处测试的所有组合物中机械性能最佳的材料，同时，它提供了一个适合细胞平衡黏附和软骨生成分化的环境。因此，它代表了一种极有潜力用作软骨再生治疗的可注射材料的体系。
