Improved Wound Closure Rates and Mechanical Properties Resembling Native Skin in Murine Diabetic Wounds Treated with a Tropoelastin and Collagen Wound Healing Device

Abstract

Chronic wounds in patients suffering from type II diabetes mellitus (DMII) where wounds remain open with a complicated pathophysiology, healing, and recovery process is a public health concern. Normal wound healing plays a critical role in wound closure, restoration of mechanical properties, and the biochemical characteristics of the remodeled tissue. Biological scaffolds provide a tissue substitute to help facilitate wound healing by mimicking the extracellular matrix (ECM) of the dermis. In the current study an electrospun biomimetic scaffold, wound healing device (WHD), containing tropoelastin (TE) and collagen was synthesized to mimic the biochemical and mechanical characteristics of healthy human skin. The WHD was compared to a commercially available porcine small intestinal submucosa (SIS) matrix that has been used in both partial and full-thickness wounds, Oasis ® Wound Matrix. Using a diabetic murine model C57BKS.Cg-m+/+Leprdb/J mice (db/db) wound closure rates, histochemistry (CD31 and CD163), qPCR (GAPDH, TNF-α, NOS2, ARG1 and IL10), and mechanical testing of treated wound sites were evaluated. The WHD in a splinted, full thickness, diabetic murine wound healing model demonstrated skin organ regeneration, an enhanced rate of wound closure, decreased tissue inflammation, and a stronger and more durable remodeled tissue that more closely mimics native unwounded skin compared to the control device.

Enhancing diabetic wound healing: advances in electrospun scaffolds from pathogenesis to therapeutic applications

“…In vitro and in vivo experiments demonstrated that PVA/EPP1 fiber scaffolds accelerated wound repair in diabetic mice. Kellar et al (2020) investigated the synthesis of electrospun biomimetic scaffolds containing Tropoelastin (TE) and collagen. In vivo experiments using a diabetic mouse model revealed that the scaffold group exhibited increased neoplastic skin tissue, faster wound healing, reduced inflammatory response, and closer resemblance to unwounded skin compared to the control group.…”

Sterilized human skin graft with a dose of 25 kGy provides a privileged immune and collagen microenvironment in the adhesion of Nude mice wounds

“…At this stage, fibroblasts mainly secrete type III collagen, forming granulation tissue. Furthermore, fibroblasts can differentiate into myofibroblasts, which have the contractile capacity to reach the wound edges, besides neoangiogenesis results in the vascularization of the dermis and the proliferation of keratinocytes favors the re-epithelialization and closure of the epidermis [ 5 – 7 ]. The remodeling phase is characterized by extracellular matrix remodeling, replacing scar tissue with a physiological matrix, constituted mainly of Col I [ 6 , 8 , 9 ].…”