Controlled delivery of bFGF to recipient bed enhances the vascularization and viability of an ischemic skin flap

Abstract

Therapeutic angiogenesis is a promising approach to treat ischemic skin flaps. We delivered basic fibroblast growth factor (bFGF) to the recipient bed of a rat dorsal skin flap by a drug delivery system with acidic gelatin hydrogel microspheres (AGHMs), and assessed augmentation of neovascularization and flap viability. An axial skin flap was elevated on the back of male Sprague-Dawley rats, and bFGF solution or bFGF-impregnated AGHMs were injected into the recipient bed. The dose of bFGF in the bFGF solution was set to 15 (Sol-15 group), 50 (Sol-50 group), or 150 mug (Sol-150 group). Correspondingly, 2 mg AGHMs were impregnated with 15 (AGHM-15 group), 50 (AGHM-50 group), or 150 mug (AGHM-150 group) bFGF. Other groups of animals received phosphate-buffered saline (Sol-Cont group) or phosphate-buffered saline-impregnated AGHMs (AGHM-Cont group) as controls. Seven days later, analyses of the area of necrosis, microangiographic findings, and histological findings in the flap were carried out. The area of necrosis in the AGHM-150 group was significantly smaller than that in the other groups. Microangiographic and histological analyses showed that neovascularization of the ischemic skin flap significantly increased in the AGHM-150 group as compared with the Sol-150 group and the AGHM-Cont group. These findings suggest that continuous delivery of bFGF to the recipient bed by bFGF-impregnated AGHMs enhances the viability of an ischemic skin flap.

Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

“…The need for experimental models of ischemic wounds is therefore compelling. Skin flaps represent a proven classical approach to induce ischemia (5,6,(21)(22)(23). In this study, the flap dimensions were optimized such that the tissue was ischemic but not necrotic.…”

Characterization of a preclinical model of chronic ischemic wound

“…Using the re-epithelialized area as the numerator and the original width as the denominator and multiplying by 100 gives the percentage of the wound re-epithelialized (E/W) ϫ 100 ϭ percent re-epithelialization. Data are means Ϯ SD (n ϭ 3); *P Ͻ 0.05. classical approach to induce ischemia (14,27,28,37,60). In this study, the flap dimensions were optimized such that the tissue was ischemic but not necrotic.…”

Role of sensory and motor intensity of electrical stimulation on fibroblastic growth factor-2 expression, inflammation, vascularization, and mechanical strength of full-thickness wounds

“…In our previous study, we reported that sensory ES can induce greater release of VEGF on day 7 after incisional wounding [16]. It seems that FGF-2 plays some role in VEGF signaling and upregulation of VEGF expression [7,39]. Thus, according to results of the present study and those of our previous study, sensory ES, via an increase in expression of FGF-2 during the early phase of healing, may induce upregulation of VEGF during the proliferation phase of the healing process.…”