An Evaluation of an Implantable Growth Factor …



An Evaluation of an Implantable Growth Factor Impregnated Drug Delivery System in a Diabetic Wound Healing Model

Introduction: Polypeptide growth factors have stimulated an enormous surge in wound healing research. Investigators have shown cytokine augmentation of wound healing in a variety of models. Studies have revealed that this augmentation is more clinically significant for chronic, nonhealing wounds such as the diabetic state. To this end, impaired wound healing models with clinical applicability have been developed to determine the impact and modulation of growth factors on wound dynamics. The present work sought to investigate a growth factor drug delivery system containing TGF-B and FGF upon wound healing in a diabetic model.

Methods & Materials: Sixty Sprague-Dawley rats were included in the study. Intraperitoneal streptozocin

induction of 48 animals was performed with serum blood sugar measurements to confirm conversion to the diabetic state; 12 animals served as non-diabetic controls. Five study groups(n=12) were designed as follows: non-diabetic control, DDS(drug delivery system)/FGF, DDS/TGF-beta, DDS/FGF+TGF-beta, absent DDS. Subsequently, dorsal skin incisions were performed and the DDS/growth factors were implanted. On post wounding days 4,7, and 14 euthanization of 4 rats in each group was performed. Wounds were analyzed histologically for cellularity and collagen architecture. Wound breaking strength was analyzed using a Dynastat Tensiometer.

Results: The diabetic rat model demonstrated significantly impaired wound breaking strength when compared to non-diabetic controls, substantiating the model for growth factor analysis. Throughout all time points, there was a positive effect of TGF-beta growth factor in reversing impaired wound healing. There was an additive effect when both growth factors are used, however FGF alone was not statistically significant. By day 14, there was a significant difference between addition of both growth factors versus the diabetic control. Further, there was no difference between the group with both growth factors and the non-diabetic control demonstrating near full return to normal wound healing with supplementation of growth factors. Statistical analysis was performed via two way analysis of variance, student-newman-keuls method. Histologic specimens were remarkable for improved collagen architecture in growth factor treated wound versus the diabetic samples, particularly in the combined growth factor grouping.

Conclusion: The growth factor drug delivery system demonstrated significant modulation and improvement of wound healing in the diabetic model. The DDS enables us to locally administer growth factors in controlled doses via a predictable time release manner. In particular, the synergy of FGF/TGF-beta nearly fully restores wound characteristics to the non-compromised state. Hence, controlled drug delivery systems can be utilized to reverse the impact of diabetic wound sequalae.

References

1. Mellin TN et al: Acidic Fibroblast growth factor accelerates dermal wound healing. Growth Factors 7:1-14, 1992.

2. Bitar MS et al: Transforming Growth Factor-b and Insulin-like Growth Factor-I in Relation to Diabetes-Induced Impairment of Wound Healing. Journal of Surgical Research 61:113-119, 1996.

3. Goodson WH and Hunt TK. Studies of Wound Healing in Experimental Diabetes. J. Surg Res. 22: 221, 1977

4. Levenson SM et. al: The Healing of Rat Skin Wounds. Ann. Surg. 161: 293, 1965

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