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Updated: Jul 19, 2026
A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming
J M Davidson1, K N Broadley1, D Quaglino
1Research Service, Department of Veterans Affairs Medical Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Abstract:
Wound healing is impaired in the diabetic state because of, at least in part, low expression of growth factors. Individual growth factors can partially activate healing, yet the actual wound environment presents a dynamic continuum of multiple cellular signals. Complex interactions among growth factors and target cells can have synergistic effects, and several examples of combinatorial, in vivo activity are evident in the literature. In this study, the implantation of a combination of basic fibroblast growth factor and transforming growth factor-beta in rats induced fivefold to sevenfold increases in granulation tissue formation in comparison with implantation of each growth factor alone. Diabetes was induced in adult, male Sprague-Dawley rats with streptozotocin. Incisional wounds and sponge granulation tissue were produced in separate groups and then treated with an injection of 2 microg transforming growth factor-beta1 combined with 10 microg basic fibroblast growth factor on day 3. DNA, collagen, and protein were analyzed in granulation tissue on days 7 and 9, and biomechanical properties of incisions were tested on days 7, 14, and 21. The combination of transforming growth factor-beta1 and basic fibroblast growth factor had marked, positive effects on biochemical parameters of wound healing and reversed the tensile strength deficit of diabetic wounds. Nonradioactive in situ hybridization showed increased expression of messenger RNA for type I and III procollagen and transforming growth factor-beta1 in normal and diabetic wounds, whereas ultrastructural examination showed a marked reorganization of collagen fibrils. These findings reinforce the concept that appropriate mixtures of cytokines rather than individual cytokines may more adequately stimulate tissues in cases of impaired wound healing.
Insights
Diabetic wound healing is poor due to low growth factors. Combining basic fibroblast growth factor and transforming growth factor-beta significantly enhanced healing and reversed strength deficits in diabetic rats.
Area of Science:
- Biomedical science
- Wound healing research
- Diabetic complications
Background:
- Diabetic state impairs wound healing, partly due to reduced growth factor expression.
- Individual growth factors offer limited therapeutic benefit in complex wound environments.
- Synergistic effects of combined growth factors are crucial for effective wound repair.
Purpose of the Study:
- To investigate the efficacy of combined basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-β1) in enhancing diabetic wound healing.
- To evaluate the impact of this combination therapy on granulation tissue formation, collagen synthesis, and wound tensile strength in diabetic rats.
Main Methods:
- Adult male Sprague-Dawley rats were induced with diabetes using streptozotocin.
- Incisional and sponge granulation tissue models were used.
- Wounds were treated with a combination of TGF-β1 (2 μg) and bFGF (10 μg) on day 3.
- Biochemical analysis (DNA, collagen, protein) and biomechanical testing were performed.
Main Results:
- The combination of TGF-β1 and bFGF significantly increased granulation tissue formation (5-7 fold) compared to individual factors.
- Biochemical parameters of wound healing were markedly improved.
- The tensile strength deficit in diabetic wounds was reversed by the combined treatment.
- Increased expression of type I and III procollagen and TGF-β1 mRNA was observed.
Conclusions:
- Appropriate mixtures of cytokines, specifically TGF-β1 and bFGF, are more effective than individual cytokines for stimulating healing in impaired wound environments.
- Combined growth factor therapy holds promise for treating chronic diabetic wounds.
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