Gene transfer of insulin-like growth factor (IGF-1) improves wound healing in diabetic full-thickness porcine wounds

The goals of this study are to develop a high purity patented silk fibroin (SF) film and test its suitability to be used as a slow-release delivery for insulin-like growth factor-1 (IGF-1). The release rate of the SF film delivering IGF-1 followed zero-order kinetics as determined via the Ritger and Peppas equation. The release rate constant was identified as 0.11, 0.23, and 0.09% h−1 at 37 °C for SF films loaded with 0.65, 6.5, and 65 pmol IGF-1, respectively. More importantly, the IGF-1 activity was preserved for more than 30 days when complexed with the SF film. We show that the IGF-1-loaded SF films significantly accelerated wound healing in vitro (BALB/3T3) and in vivo (diabetic mice), compared with wounds treated with free IGF-1 and an IGF-1-loaded hydrocolloid dressing. This was evidenced by a six-fold increase in the granulation tissue area in the IGF-1-loaded SF film treatment group compared to that of the PBS control group. Western blotting analysis also demonstrated that IGF-1 receptor (IGF1R) phosphorylation in diabetic wounds increased more significantly in the IGF-1-loaded SF films group than in other experimental groups. Our results suggest that IGF-1 sustained release from SF films promotes wound healing through continuously activating the IGF1R pathway, leading to the enhancement of both wound re-epithelialization and granulation tissue formation in diabetic mice. Collectively, these data indicate that SF films have considerable potential to be used as a wound dressing material for long-term IGF-1 delivery for diabetic wound therapy.

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Local induction of an insulin-like growth factor binding protein-3 degrading protease activity in the course of wound healing

Wound Repair and Regeneration ◽

10.1046/j.1524-475x.1996.40214.x ◽

1996 ◽

Vol 4 (2) ◽

pp. 252-258 ◽

Cited By ~ 2

Author(s):

Karl Fournier ◽

Catherine Tavera ◽

Paul Brazeau ◽

Thierry Abribat

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Protease Activity ◽

Binding Protein ◽

Insulin Like Growth Factor ◽

Factor Binding

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Effect of Therapy with Recombinant Human Growth Hormone on Insulin-Like Growth Factor System Components and Serum Levels of Biochemical Markers of Bone Formation in Children After Severe Burn Injury1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.1.4518 ◽

1998 ◽

Vol 83 (1) ◽

pp. 21-24 ◽

Cited By ~ 1

Author(s):

Gordon L. Klein ◽

Steven E. Wolf ◽

Craig B. Langman ◽

Clifford J. Rosen ◽

Subburaman Mohan ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Bone Formation ◽

Binding Protein ◽

Serum Levels ◽

Controlled Study ◽

Type I ◽

Insulin Like Growth Factor ◽

Type I Procollagen ◽

Igfbp 3

Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone formation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg·day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 ± 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level. IGFBP-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.

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