Gila-Vilchez Cristina, Mañas-Torres Mari Carmen, García-García Óscar Darío, Escribano-Huesca Alfredo, Rodríguez-Arco Laura, Carriel Víctor, Rodriguez Ismael, Alaminos Miguel, Lopez-Lopez Modesto Torcuato, Álvarez de Cienfuegos Luis
Departamento de Física Aplicada, Universidad de Granada (UGR), C. U. Fuentenueva, Avenida Severo Ochoa s/n, E-18071 Granada, Spain.
Instituto de Investigación Biosanitaria ibs.GRANADA, Avenida de Madrid, 15, 18016, Granada, Spain.
ACS Appl Polym Mater. 2023 Feb 21;5(3):2154-2165. doi: 10.1021/acsapm.2c02164. eCollection 2023 Mar 10.
Fibrin hydrogels made by self-assembly of fibrinogen obtained from human plasma have shown excellent biocompatible and biodegradable properties and are widely used in regenerative medicine. The fibrinogen self-assembly process can be triggered under physiological conditions by the action of thrombin, allowing the injection of pregel mixtures that have been used as cell carriers, wound-healing systems, and bio-adhesives. However, access to fibrinogen from human plasma is expensive and fibrin gels have limited mechanical properties, which make them unsuitable for certain applications. One solution to these problems is to obtain composite gels made of fibrin and other polymeric compounds that improve their mechanical properties and usage. Herein, we prepared composite hydrogels made by the self-assembly of fibrinogen together with Fmoc-FF (Fmoc-diphenylalanine) and Fmoc-RGD (Fmoc-arginine-glycine-aspartic acid). We have shown that the mixture of these three peptides co-assembles and gives rise to a unique type of supramolecular fiber, whose morphology and mechanical properties can be modulated. We have carried out a complete characterization of these materials from chemical, physical, and biological points of view. Composite gels have improved mechanical properties compared to pure fibrin gels, as well as showing excellent biocompatibility ex vivo. In vivo experiments have shown that these gels do not cause any type of inflammatory response or tissue damage and are completely resorbed in short time, which would enable their use as vehicles for cell, drug, or growth factor release.
由人血浆中提取的纤维蛋白原自组装制成的纤维蛋白水凝胶具有优异的生物相容性和可生物降解性,在再生医学中得到广泛应用。纤维蛋白原的自组装过程可在生理条件下由凝血酶触发,从而能够注射用作细胞载体、伤口愈合系统和生物粘合剂的预凝胶混合物。然而,从人血浆中获取纤维蛋白原成本高昂,且纤维蛋白凝胶的机械性能有限,这使得它们不适用于某些应用。解决这些问题的一种方法是获得由纤维蛋白和其他聚合物化合物制成的复合凝胶,以改善其机械性能和用途。在此,我们制备了由纤维蛋白原与Fmoc-FF(Fmoc-二苯基丙氨酸)和Fmoc-RGD(Fmoc-精氨酸-甘氨酸-天冬氨酸)自组装而成的复合水凝胶。我们已经表明,这三种肽的混合物会共同组装并产生一种独特类型的超分子纤维,其形态和机械性能可以被调节。我们已经从化学、物理和生物学角度对这些材料进行了全面表征。与纯纤维蛋白凝胶相比,复合凝胶具有更好的机械性能,并且在体外也表现出优异的生物相容性。体内实验表明,这些凝胶不会引起任何类型的炎症反应或组织损伤,并且在短时间内会完全被吸收,这使得它们能够用作细胞、药物或生长因子释放的载体。