RGTA OTR 4120, a heparan sulfate proteoglycan mimetic, increases wound breaking strength and vasodilatory capability in healing rat full‐thickness excisional wounds

Abstract

ReGeneraTing Agents (RGTAs), a family of polymers engineered to protect and stabilize heparin-binding growth factors, have been shown to promote tissue repair and regeneration. In this study, the effects of one of these polymers, RGTA OTR4120, on healing of full-thickness excisional wounds in rats were investigated. Two 1.5 cm diameter circular full-thickness excisional wounds were created on the dorsum of a rat. After creation of the wounds, RGTA OTR4120 was applied. The progress of healing was assessed quantitatively by evaluating the wound closure rate, vasodilatory capability, and wound breaking strength. The results showed a triple increase of the local vascular response to heat provocation in the RGTA OTR4120-treated wounds as compared with vehicle-treated wounds. On days 14 and 79 after surgery, the wounds treated with RGTA OTR4120 gained skin strength 12% and 48% of the unwounded skin, respectively, and displayed a significantly increased gain in skin strength when compared with control animals. These results raise the possibility of efficacy of RGTA OTR4120 in accelerating surgically cutaneous wound healing by enhancing the wound breaking strength and improving the microcirculation.Wound healing is a dynamic and complex process of tissue repair, that involves a number of cellular and molecular events. These events include cell migration, proliferation, angiogenesis, and extracellular matrix (ECM) deposition and degradation.

Heparan Sulfate Proteoglycan Mimetics Promote Tissue Regeneration: An Overview

“…** p<0.01 and *** p < 0.001 indicate the significant differences between treated groups and control groups. (Tong, Zbinden et al 2008) 6.4.4 Ischemia-reperfusion wounds Tong et al (2011) also studied the effects of RGTA OTR4120 administration to ischemiareperfusion wounds (Tong, Tuk et al 2011). Similar findings as for the excisional wounds were observed in a cutaneous ischemia-reperfusion model obtained by magnet clamping of a skin fold in the neck area of the animal although with a delayed timing due to the clearance of the necrotic tissue (Tong, Tuk et al 2011).…”

“…RGTA OTR4120 administration to surgical wounds in rapid healing normal rats significantly improved wound regeneration. RGTA OTR4120 administration promotes epidermal proliferation, increased neodermal granulation tissue deposition, inflammation resolution, improved the vascular response to local heating (Figure 7a), improved collagen maturation and improved the wound breaking strength at all measurement times up to 3 months post wounding ( Figure 7b) (Tong, Zbinden et al 2008;Tong, Tuk et al 2009). Fig.…”

“…Excess RGTA OTR4120 may compete with sites on the matrix-bound RGTA for heparan binding growth factors. In following phases of wound regeneration a weekly administration also proofed to be effective (Tong, Zbinden et al 2008;Barbier-Chassefiere, Garcia-Filipe et al 2009). No specific studies are reported to further optimize the timing of RGTA OTR4120 application.…”

“…Dermal effects of RGTA OTR4120 administration are described in necrotic skin ulcers in mice (BarbierChassefiere, Garcia-Filipe et al 2009), incisional dermal wounds in rats (Barritault, GarciaFilipe et al 2010), second degree burns in rats (Garcia-Filipe, Barbier-Chassefiere et al 2007) (Zakine, Barbier et al 2011), a rat surgical excision model (Tong, Zbinden et al 2008;Tong, Tuk et al 2009;Tong, Tuk et al 2011) and in rat dermal ischemia ulcers (Tong, Tuk et al 2011). …”

“…Tong et al studied the effects of RGTA OTR4120 administration to rat full-thickness excisional wounds (Tong, Zbinden et al 2008;Tong, Tuk et al 2009). RGTA OTR4120 administration to surgical wounds in rapid healing normal rats significantly improved wound regeneration.…”