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Contraction of fibrin‐derived matrices and its implications for in vitro human skin bioengineering
Journal of Biomedical Materials Research Part A ( IF 4.9 ) Pub Date : 2020-06-07 , DOI: 10.1002/jbm.a.37033
Andrés Montero 1 , Sonia Acosta 1 , Rebeca Hernández 2 , Carlos Elvira 3 , José Luis Jorcano 1, 4 , Diego Velasco 1
Affiliation  

It is well‐known that fibroblasts play a fundamental role in the contraction of collagen and fibrin hydrogels when used in the production of in vitro bilayered skin substitutes. However, little is known about the contribution of other factors, such as the hydrogel matrix itself, on this contraction. In this work, we studied the contraction of plasma‐derived fibrin hydrogels at different temperatures (4, 23, and 37°C) in an isotonic buffer (phosphate‐buffered saline). These types of hydrogels presented a contraction of approximately 30% during the first 24 hr, following a similar kinetics irrespectively of the temperature. This kinetics continued in a slowed down manner to reach a plateau value of 40% contraction after 10–15 days. Contraction of commercial fibrinogen hydrogels was studied under similar conditions and the kinetics was completed after 8 hr, reaching values between 20 and 70% depending on the temperature. We attribute these substantial differences to a modulatory effect on the contraction due to plasma proteins which are initially embedded in, and progressively released from, the plasma‐based hydrogels. The elastic modulus of hydrogels measured at a constant frequency decreased with increasing temperature in 7‐day gels. Rheological measurements showed the absence of a strain‐hardening behavior in the plasma‐derived fibrin hydrogels. Finally, plasma‐derived fibrin hydrogels with and without human primary fibroblast and keratinocytes were prepared in transwell inserts and their height measured over time. Both cellular and acellular gels showed a height reduction of 30% during the first 24 hr likely due to the above‐mentioned intrinsic fibrin matrix contraction.

中文翻译:

纤维蛋白衍生基质的收缩及其对体外人体皮肤生物工程的影响

众所周知,当用于生产体外双层皮肤替代品时,成纤维细胞在胶原蛋白和纤维蛋白水凝胶的收缩中起重要作用。然而,关于其他因素(例如水凝胶基质本身)对这种收缩的贡献知之甚少。在这项工作中,我们研究了血浆来源的纤维蛋白水凝胶在等渗缓冲液(磷酸盐缓冲盐水)中在不同温度(4、23 和 37°C)下的收缩。这些类型的水凝胶在第一个 24 小时内呈现大约 30% 的收缩,无论温度如何,都遵循类似的动力学。这种动力学以减慢的方式继续,在 10-15 天后达到收缩 40% 的平台值。在类似条件下研究商业纤维蛋白原水凝胶的收缩,8 小时后完成动力学,根据温度达到 20% 到 70% 之间的值。我们将这些实质性差异归因于血浆蛋白对收缩的调节作用,血浆蛋白最初嵌入基于血浆的水凝胶中,并逐渐从血浆水凝胶中释放出来。在 7 天凝胶中,在恒定频率下测量的水凝胶的弹性模量随着温度的升高而降低。流变学测量表明,血浆来源的纤维蛋白水凝胶不存在应变硬化行为。最后,在 transwell 插入物中制备了含有和不含人类原代成纤维细胞和角质形成细胞的血浆衍生纤维蛋白水凝胶,并随着时间的推移测量它们的高度。
更新日期:2020-06-07
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