Development of poly(vinylpyrrolidinone) newtorks for treatment of skin graft contracture.

Skin graft contracture is a problem facing many bums patients treated with skin
grafts. Currently grafts under suspicion of contraction are treated with pressure
garments to prevent contractures progressing. Patients may have to wear these for
many months however once contractures have formed surgical intervention is
commonly required.
The aim of this project was to develop a hydrogel drug delivery system to prevent or
reduce skin graft contracture. Two potential anti-contraction agents, identified based
on prior work from our laboratory were initially examined for their effectiveness in
preventing contracture formation using two 3D models of contraction - collagen I
gels and a reconstructed human skin model. 13-aminopropionitrile (13APN), a noncompetitive
lysyl oxidase inhibitor significantly reduced contraction in the
reconstructed skin model but not the collagen gel model while 4-methyl
umbelliferone (4-MU) reduced contraction in both models.
For hydrogel drug delivery poly(N-vinylpyrrolidinone) (PNVP) hydrogels were
developed with material properties suitable for use as a non-cytotoxic wound
dressing. Two crosslinked PNVP's were investigated, one crosslinked with ethylene
glycol dimethacrylate (EGDMA) and the other crosslinked with diethyleneglycol bis
allylcarbonate (DEGBAC). The different crosslinkers led to hydrogels with different
mechanical and slightly different biological properties. Although neither hydrogel
proved to be suitable for culturing cells on, indirect contact with both showed them
to be biocompatible and in some cases stimulatory to fibroblasts. These hydrogels
were evaluated for their uptake and release of 13APN and 4-MU. Hydrogels were
then used to deliver 13APN and 4-MU to reduce skin cell contraction in both collagen
gels and the reconstructed skin model with some promising preliminary results
showing hydrogels releasing 4-MU to reduce contraction in the 3D collagen gel
model.