Stojic Marija, Ródenas-Rochina Joaquín, López-Donaire María Luisa, González de Torre Israel, González Pérez Miguel, Rodríguez-Cabello José Carlos, Vojtová Lucy, Jorcano José Luis, Velasco Diego
CEITEC-Central European Institute of Technology, Brno University of Technology, Purkyňova 123, 61200 Brno, Czech Republic.
Department of Bioengineering & Aerospace Engineering, University Carlos III of Madrid (UC3M), Avenida Universidad 30, 28911 Leganés, Spain.
Polymers (Basel). 2021 Jun 28;13(13):2114. doi: 10.3390/polym13132114.
Dermo-epidermal equivalents based on plasma-derived fibrin hydrogels have been extensively studied for skin engineering. However, they showed rapid degradation and contraction over time and low mechanical properties which limit their reproducibility and lifespan. In order to achieve better mechanical properties, elasticity and biological properties, we incorporated a elastin-like recombinamer (ELR) network, based on two types of ELR, one modified with azide (SKS-N) and other with cyclooctyne (SKS-Cyclo) chemical groups at molar ratio 1:1 at three different SKS (serine-lysine-serine sequence) concentrations (1, 3, and 5 wt.%), into plasma-derived fibrin hydrogels. Our results showed a decrease in gelation time and contraction, both in the absence and presence of the encapsulated human primary fibroblasts (hFBs), higher mechanical properties and increase in elasticity when SKSs content is equal or higher than 3%. However, hFBs proliferation showed an improvement when the lowest SKS content (1 wt.%) was used but started decreasing when increasing SKS concentration at day 14 with respect to the plasma control. Proliferation of human primary keratinocytes (hKCs) seeded on top of the hybrid-plasma hydrogels containing 1 and 3% of SKS showed no differences to plasma control and an increase in hKCs proliferation was observed for hybrid-plasma hydrogels containing 5 wt.% of SKS. These promising results showed the need to achieve a balance between the reduced contraction, the better mechanical properties and biological properties and indicate the potential of using this type of hydrogel as a testing platform for pharmaceutical products and cosmetics, and future work will elucidate their potential.
基于血浆衍生纤维蛋白水凝胶的真皮-表皮等效物已在皮肤工程领域得到广泛研究。然而,随着时间的推移,它们表现出快速降解和收缩,以及较低的机械性能,这限制了它们的可重复性和使用寿命。为了获得更好的机械性能、弹性和生物学特性,我们将一种基于两种弹性蛋白样重组蛋白(ELR)的网络,以1:1的摩尔比、三种不同的SKS(丝氨酸-赖氨酸-丝氨酸序列)浓度(1%、3%和5%重量),一种用叠氮化物修饰(SKS-N),另一种用环辛炔(SKS-Cyclo)化学基团修饰,掺入血浆衍生的纤维蛋白水凝胶中。我们的结果表明,无论是否存在包封的人原代成纤维细胞(hFBs),凝胶化时间和收缩都有所减少,当SKSs含量等于或高于3%时,机械性能更高且弹性增加。然而,当使用最低的SKS含量(1%重量)时,hFBs增殖有所改善,但在第14天相对于血浆对照增加SKS浓度时开始下降。接种在含有1%和3% SKS的混合血浆水凝胶顶部的人原代角质形成细胞(hKCs)的增殖与血浆对照没有差异,而对于含有5%重量SKS的混合血浆水凝胶,观察到hKCs增殖增加。这些有前景的结果表明,需要在减少收缩、更好的机械性能和生物学特性之间取得平衡,并表明使用这种类型的水凝胶作为药品和化妆品测试平台的潜力,未来的工作将阐明它们的潜力。