Novel fibrin-fibronectin matrix accelerates mice skin wound healing

Plasma fibrinogen(F1)and fibronectin(pFN)polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing.About 90%of plasma F1 has a homodimeric pair ofγchains(γγF1),and 10%has a heterodimeric pair ofγand more acidicγ′chains(γγ′F1).We have synthesized a novel fibrin matrix exclusively from a 1:1(molar ratio)complex ofγγ′F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII(rFXIIIa).In this matrix,the fibrin nanofibers were decorated with pFN nanoclusters(termedγγ′F1:pFN fibrin).In contrast,fibrin made from 1:1 mixture ofγγF1 and pFN formed a sporadic distribution of“pFN droplets”(termedγγF1+pFN fibrin).Theγγ′F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells(HUVECs)relative to theγγF1+FN fibrin.Three dimensional(3D)culturing showed that theγγ′F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts.HUVECs in the 3Dγγ′F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in theγγF1+pFN fibrin.Relative toγγF1+pFN fibrin,mouse dermal wounds that were sealed byγγ′F1:pFN fibrin exhibited accelerated and enhanced healing.This study suggests that a 3D pFN presentation on a fibrin matrix promotes wound healing.