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Abstract

The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse model. The effect of several formulation variables, dose, and application frequency was examined. It was found that wound healing in diabetic animals treated with aFGF or placebo was slower than in their nondiabetic littermates. The availability of aFGF from the viscous vehicle employed in this study (1% hydroxyethyl cellulose) was demonstrated in vitro using diffusion cells. The viscous formulation of aFGF was equally effective in wound healing as a nonviscous formulation in phosphate-buffered saline. A formulation containing heparin (necessary for full biological and conformational stability of aFGF) at a mass ratio of 3:1 to aFGF was more efficacious than formulations with lower heparin: aFGF ratios. Wounds treated with three doses of 3.0 micrograms/cm2 aFGF healed faster than those treated with a single dose of 3.0 micrograms/cm2 aFGF. Three applications of 3.0 or 0.6 microgram/cm2 a FGF were equally effective in accelerating wound healing.

Royal jelly enhances migration of human dermal fibroblasts and alters the levels of cholesterol and sphinganine in anin vitrowound healing model

“…3A). In contrast to our results, previous reports found that in cultured skin substitutes grown in vitro the levels of cholesterol and free fatty acids were increased during the healing process with grafting [10,26]. An increase in the levels of lipids in HDFn, in particular sphingolipids such as ceramides and glucosylceramides, has been noted to occur in the wound healing process [27,28].…”

“…An increase in the levels of lipids in HDFn, in particular sphingolipids such as ceramides and glucosylceramides, has been noted to occur in the wound healing process [27,28]. Also, increases in the levels of glucosylceramides and ceramides were highly distinct [26,29]. However, despite a dose-dependent increase in sphinganine, no alterations in sphingosine levels were noted with any concentration of RJ in our investigation (Fig.…”

“…Concomitantly, wound formation also increases the generation of PPAR β ligands, which include several sphingolipids [31,33,36,38,39]. The resulting increase in the level of PPAR β transcription activity ultimately accelerates the viability, adhesion, and migration of HDFn during the wound healing process [19,26,36,37,40]. …”

Pharmacokinetic Properties of 2nd-Generation Fibroblast Growth Factor-1 Mutants for Therapeutic Application

“…However, heparin is more expensive than FGF-1 to produce, is derived from pigs (with the potential for infectious agents), is highly heterogeneous, has its own (anti-coagulant) pharmacological properties, can initiate a serious allergic reaction, and can cause thrombocytopenia [26], [27]. Furthermore, while the treatment of coronary ischemia by FGF-1 has shown effectiveness with a single (injected) dose, healing of wounds is best achieved with multiple (topical) dosing – necessitating frequent removal of bandages for access to the wound area [8]–[10], [28]. This latter issue is complicated by the presence of heparin, which, due to its pharmacological properties, causes wounds to produce excessive exudate, diluting topically-applied therapeutics.…”

Fibroblast growth factors, old kids on the new block

“…FGF1 induces cell proliferation in the wounded area and promotes the cells to produce cytokines and other growth factors that induce migration of macrophages and monocytes towards the wounded area to remove damaged or dead cells (119, 120). FGF1 also induces epithelial cells and vessel endothelial cells to migrate toward the healing tissues.…”