Introduction: Polypeptide growth factors have stimulated an enormous surge in wound healing research. 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 as well as by wound breaking strength analysis.
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 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 wounds versus the diabetic samples.
Conclusion: The growth factor drug delivery system demonstrated significant modulation and improvement of wound healing in the diabetic model. 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.