Abdallah Maya, Nagarajan Sakthivel, Martin Marta, Tamer Marleine, Faour Wissam H, Bassil Maria, Cuisinier Frederic J G, Gergely Csilla, Varga Bela, Pall Orsolya, Miele Philippe, Balme Sebastien, El Tahchi Mario, Bechelany Mikhael
Institut Européen des Membranes, IEM UMR 5635, Univ Montpellier, ENSCM, CNRS, Montpellier 34095, France.
Laboratoire Charles Coulomb, Université de Montpellier, CNRS, Montpellier 34095, France.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7531-7539. doi: 10.1021/acsabm.0c00734. Epub 2020 Oct 29.
Biological activities of cells such as survival and differentiation processes are mainly maintained by a specific extracellular matrix (ECM). Hydrogels have recently been employed successfully in tissue engineering applications. In particular, scaffolds made of gelatin methacrylate-based hydrogels (GelMA) showed great potential due to their biocompatibility, biofunctionality, and low mechanical strength. The development of a hydrogel having tunable and appropriate mechanical properties as well as chemical and biological cues was the aim of this work. A synthetic and biological hybrid hydrogel was developed to mimic the biological and mechanical properties of native ECM. A combination of gelatin methacrylate and acrylamide (GelMA-AAm)-based hydrogels was studied, and it showed tunable mechanical properties upon changing the polymer concentrations. Different GelMA-AAm samples were prepared and studied by varying the concentrations of GelMA and AAm (AAm + GelMA, AAm + GelMA, and AAm + GelMA). The swelling behavior, biodegradability, physicochemical and mechanical properties of GelMA-AAm were also characterized. The results showed a variation of swelling capability and a tunable elasticity ranging from 4.03 to 24.98 kPa depending on polymer concentrations. Moreover, the podocyte cell morphology, cytoskeleton reorganization and differentiation were evaluated as a function of GelMA-AAm mechanical properties. We concluded that the AAm + GelMA hydrogel sample having an elasticity of 4.03 kPa can mimic the native kidney glomerular basement membrane (GBM) elasticity and allow podocyte cell attachment without the functionalization of the gel surface with adhesion proteins compared to synthetic hydrogels (PAAm). This work will further enhance the knowledge of the behavior of podocyte cells to understand their biological properties in both healthy and diseased states.
细胞的生物活性，如存活和分化过程，主要由特定的细胞外基质（ECM）维持。水凝胶最近已成功应用于组织工程领域。特别是，基于甲基丙烯酸明胶的水凝胶（GelMA）制成的支架由于其生物相容性、生物功能性和低机械强度而显示出巨大潜力。开发一种具有可调且合适机械性能以及化学和生物学线索的水凝胶是这项工作的目标。一种合成与生物混合的水凝胶被开发出来，以模拟天然ECM的生物学和机械性能。对基于甲基丙烯酸明胶和丙烯酰胺（GelMA-AAm）的水凝胶组合进行了研究，结果表明改变聚合物浓度时其机械性能可调。通过改变GelMA和AAm的浓度（AAm + GelMA、AAm + GelMA和AAm + GelMA）制备并研究了不同的GelMA-AAm样品。还对GelMA-AAm的溶胀行为、生物降解性、物理化学和机械性能进行了表征。结果表明，溶胀能力有所变化，弹性可在4.03至24.98 kPa之间调节，具体取决于聚合物浓度。此外，还评估了足细胞的细胞形态、细胞骨架重组和分化与GelMA-AAm机械性能的关系。我们得出结论，与合成水凝胶（PAAm）相比，弹性为4.03 kPa的AAm + GelMA水凝胶样品可以模拟天然肾肾小球基底膜（GBM）的弹性，并且在凝胶表面未用黏附蛋白功能化的情况下允许足细胞附着。这项工作将进一步增进对足细胞行为的了解，以认识其在健康和患病状态下的生物学特性。
