Topical application of
platelet-derived growth factor-BB (
PDGF-BB) is considered to accelerate tissue repair of impaired chronic
wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied
PDGF-BB, we used a controlled full thickness splinted excisional
wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined
silicone-splinted
wound model, with reduced
wound contraction, controlled
splint and
bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness
wounds were made in db/db mice.
Wounds were topically treated once daily with either 3 µg
PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days.
Body weights,
wound contraction,
wound closure, reepithelialization,
collagen content, and
wound bed
inflammation were evaluated clinically and histopathologically. The bioactivity of
PDGF-BB was confirmed by in vitro proliferation assay.
PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted
wound model. Considering that the predominant mechanism of wound healing in humans is by re-epithelialization, the most appropriate model for evaluating
therapeutics is one that uses
splints to prevent excessive
wound contraction. Here, we report that
PDGF-BB does not promote
wound closure by re-epithelialization in a murine splinted
wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the
wound model used.