Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury

Abstract

Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd.

Activated Schwann Cell-Like Cells on Aligned Fibrin-Poly(Lactic-Co-Glycolic Acid) Structures: A Novel Construct for Application in Peripheral Nerve Regeneration

“…Not only is it important for hemostasis but it also acts as a provisional growth matrix for tissue-specific cells [Wong et al, 2003]. Fibrin sealants are used in several surgical applications and have become a versatile scaffold in the field of tissue engineering, augmenting regeneration in a variety of tissues such as bone [Peled et al, 2007;Weinand et al, 2007;Kaipel et al, 2012], skin [Falanga et al, 2007;Mittermayr et al, 2013], and cartilage [Hildner et al, 2009;Hong et al, 2014]. Fibrin is an especially important factor in nerve regeneration: after an injury, nerve stumps leak fibrin plasma exudate into the affected area, forming fibrin cables that enable Schwann cells to migrate towards the distal stump and form bands of Büngner [Williams et al, 1983;Belkas et al, 2004].…”

Generation of a Fibrin Based Three-Layered Skin Substitute

“…The extracellular matrix, produced by dermal fibroblasts and ASCs, stimulates cellular growth and proliferation [ 11 ]. Further possible developments of this new multilayered model besides working with endothelial cells could be the additional use of proteins like PDGF to stimulate neovascularization [ 24 ] or incorporation of melanocytes for UV-protection [ 25 ].…”

Influence of fibrin matrices and their released factors on epidermal substitute phenotype and engraftment

“…Among those factors, IGF-1, GM-CSF, PDGF-AB, and HGF are known to stimulate keratinocyte proliferation (Shirakata, 2010). Another study also showed that some of these factors like PDGF-AB could favor the formation of a thicker epidermis once combined with a biodegradable matrix in a burn wound model (Mittermayr et al, 2016). Therefore, fibrin matrices containing growth factors are likely to enhance keratinocyte proliferation, which is important for reepithelialization and wound healing.…”