Thermosensitive hydrogel as a Tgf-beta1 gene delivery vehicle enhances diabetic wound healing.
OBJECTIVE
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.
Lee
Pui-Yan
PY
Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, 633 Salk Hall, Pittsburgh, PA 15213, USA.
Li
Zhenhua
Z
Huang
Leaf
L
D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D006358:Hot Temperature; D006801:Humans; D020100:Hydrogels; D007328:Insulin / Q000097:blood; D019344:Lactic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D014677:Pharmaceutical Vehicles; D010957:Plasmids / Q000235:genetics; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics*
D000963:Antimetabolites; D020100:Hydrogels; D007328:Insulin; D014677:Pharmaceutical Vehicles; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004247:DNA; D001973:Bromodeoxyuridine