Login / Signup

Snake venom-defined fibrin architecture dictates fibroblast survival and differentiation.

Zhao WangJan LaukoAmanda W KijasElliot Paul GilbertPetri TurunenRamanathan YegappanDongxiu ZouJitendra P MataAlan E Rowan
Published in: Nature communications (2023)
Fibrin is the provisional matrix formed after injury, setting the trajectory for the subsequent stages of wound healing. It is commonly used as a wound sealant and a natural hydrogel for three-dimensional (3D) biophysical studies. However, the traditional thrombin-driven fibrin systems are poorly controlled. Therefore, the precise roles of fibrin's biophysical properties on fibroblast functions, which underlie healing outcomes, are unknown. Here, we establish a snake venom-controlled fibrin system with precisely and independently tuned architectural and mechanical properties. Employing this defined system, we show that fibrin architecture influences fibroblast survival, spreading phenotype, and differentiation. A fine fibrin architecture is a key prerequisite for fibroblast differentiation, while a coarse architecture induces cell loss and disengages fibroblast's sensitivity towards TGF-β1. Our results demonstrate that snake venom-controlled fibrin can precisely control fibroblast differentiation. Applying these biophysical principles to fibrin sealants has translational significance in regenerative medicine and tissue engineering.
Keyphrases
  • wound healing
  • platelet rich plasma
  • tissue engineering
  • drug delivery
  • type diabetes
  • cell therapy
  • molecular dynamics
  • insulin resistance
  • weight loss