Three-Dimensional (3D) Fibronectin Nano-Array Presented on Fibrin Matrix Accelerates Mice Skin Wound Healing

Jara, C. P.; Wang, O.; Prado, T. P. d.; Ismail, A.; Fabian, F. M.; Li, H.; Velloso, L. A.; Carlson, M. A.; Burgess, W.; Lei, Y.; Velander, W. H.; Araujo, E. P.

doi:10.1101/2020.05.04.077891

bioRxiv · 10.1101/2020.05.04.077891

Three-Dimensional (3D) Fibronectin Nano-Array Presented on Fibrin Matrix Accelerates Mice Skin Wound Healing

Jara, C. P.·Wang, O.·Prado, T. P. d.·Ismail, A.·Fabian, F. M.·Li, H.·Velloso, L. A.·Carlson, M. A.·Burgess, W.·Lei, Y.·Velander, W. H.·Araujo, E. P.

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Abstract

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 of {gamma} chains ({gamma}{gamma}F1) and 10% has a heterodimeric pair of {gamma} and more acidic {gamma} chains ({gamma}{gamma}F1). We have synthesized a novel fibrin matrix exclusively from a 1:1 (molar ratio) complex of {gamma}{gamma}F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII (rFXIIIa). In this matrix, the fibrin nanofibers were wrapped with periodic 200-300 nm wide pFN nanobands (termed {gamma}{gamma}F1:pFN fibrin). In contrast, fibrin made from 1:1 mixture of {gamma}{gamma}F1 and pFN formed a sporadic distribution of "pFN droplets" (termed {gamma}{gamma}F1 +pFN fibrin). The {gamma}{gamma}F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells (HUVECs) relative to the {gamma}{gamma}F1+FN fibrin. Three dimensional (3D) culturing showed that the {gamma}{gamma}F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts. HUVECs in the 3D {gamma}{gamma}F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in the {gamma}{gamma}F1 +pFN fibrin. Relative to {gamma}{gamma}F1 +pFN fibrin, mouse dermal wounds that were sealed by {gamma}{gamma}F1:pFN fibrin exhibited accelerated and enhanced healing. This study suggests that a 3D pFN nano-array presented on a fibrin matrix can promote wound healing.

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Jara, C. P., Wang, O., Prado, T. P. d., Ismail, A., Fabian, F. M., Li, H., Velloso, L. A., Carlson, M. A., Burgess, W., Lei, Y., Velander, W. H., Araujo, E. P.. 2020-05-05. Three-Dimensional (3D) Fibronectin Nano-Array Presented on Fibrin Matrix Accelerates Mice Skin Wound Healing. https://doi.org/10.1101/2020.05.04.077891

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