Novel fibrin-fibronectin matrix accelerates mice skin wound healing

Carlos Poblete Jara; Ou Wang; Thais Paulino do Prado; Ayman Ismail; Frank Marco Fabian; Han Li; Licio A Velloso; Mark A Carlson; William Burgess; Yuguo Lei; William H Velander; Eliana P Araújo

doi:10.1016/j.bioactmat.2020.06.015

Novel fibrin-fibronectin matrix accelerates mice skin wound healing

Bioact Mater. 2020 Jul 1;5(4):949-962. doi: 10.1016/j.bioactmat.2020.06.015. eCollection 2020 Dec.

Authors

Carlos Poblete Jara^{1

2}, Ou Wang^{3

4}, Thais Paulino do Prado^{1

2}, Ayman Ismail³, Frank Marco Fabian³, Han Li^{3

5}, Licio A Velloso², Mark A Carlson^{6

7}, William Burgess³, Yuguo Lei^{3

4

7

8}, William H Velander³, Eliana P Araújo^{1

2}

Affiliations

¹ Nursing School, University of Campinas, Campinas, SP, Brazil.
² Laboratory of Cell Signaling, University of Campinas, Campinas, SP, Brazil.
³ Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE, USA.
⁴ Biomedical Engineering Program, University of Nebraska, Lincoln, NE, USA.
⁵ School of Biological Science, University of Nebraska, Lincoln, NE, USA.
⁶ Department of Surgery, University of Nebraska Medical Center and the VA Nebraska-Western Iowa Health Care System, USA.
⁷ Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, USA.
⁸ Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.

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 γ chains (γγF1), and 10% has a heterodimeric pair of γ and more acidic γ' chains (γγ'F1). We have synthesized a novel fibrin matrix exclusively from a 1:1 (molar ratio) complex of γγ'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 (termed γγ'F1:pFN fibrin). In contrast, fibrin made from 1:1 mixture of γγF1 and pFN formed a sporadic distribution of "pFN droplets" (termed γγF1+pFN fibrin). The γγ'F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells (HUVECs) relative to the γγF1+FN fibrin. Three dimensional (3D) culturing showed that the γγ'F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts. HUVECs in the 3D γγ'F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in the γγF1+pFN fibrin. Relative to γγF1+pFN fibrin, mouse dermal wounds that were sealed by γγ'F1:pFN fibrin exhibited accelerated and enhanced healing. This study suggests that a 3D pFN presentation on a fibrin matrix promotes wound healing.

Keywords: Fibrin; Fibronectin; Nanoclusters; Wound healing.