Thermosensitive hydrogel as a Tgf-beta1 gene delivery vehicle enhances diabetic wound healing.

PURPOSE: To accelerate diabetic wound healing with TGF-beta1 gene delivery system using a thermosensitive hydrogel made of a triblock copolymer, PEG-PLGA-PEG.
METHODS: Two 7 x 7 mm full thickness excisional wounds were created in parallel at the back of each genetically diabetic mouse. The hydrogel containing plasmid TGF-beta1 was administered to the wound and formed an adhesive film in situ. Controls were either untreated or treated with the hydrogel without DNA. We used a commercial wound dressing, Humatrix, either with or without DNA, to compare the therapeutic effect with the thermosensitive hydrogel.
RESULTS: We found that thermosensitive hydrogel alone is slightly beneficial for reepithealization at early stage of healing (day 1-5), but significantly accelerated repithelializaion, increased cell proliferation, and organized collagen were observed in the wound bed treated with thermosensitive hydrogel containing plasmid TGF-beta1. The accelerated reepithelialization was accompanied with enhanced collagen synthesis and more organized extracellular matrix deposition. Humatrix alone or with plasmid TGF-beta1, had little effect.
CONCLUSIONS: Thermosensitive hydrogel made of PEG-PLGA-PEG triblock copolymer provides excellent wound dressing activity and delivers plasmid TGF-beta1 to promote wound healing in a diabetic mouse model.