Contraction of fibrin-derived matrices and its implications for in vitro human skin bioengineering Articles uri icon

authors

  • MONTERO SIMON, ANDRES
  • ACOSTA, SONIA
  • HERNANDEZ, REBECA
  • ELVIRA, CARLOS
  • JORCANO NOVAL, JOSE LUIS
  • VELASCO BAYON, DIEGO

publication date

  • April 2021

start page

  • 500

end page

  • 514

issue

  • 4

volume

  • 109

International Standard Serial Number (ISSN)

  • 1549-3296

Electronic International Standard Serial Number (EISSN)

  • 1552-4965

abstract

  • 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.

keywords

  • bilayered in vitro skin substitutes; contraction of fibrin hydrogels; fibrin hydrogel; plasma-derived fibrin hydrogel; skin tissue engineering