Biodegradable polyester-urethane bilayered systems for wound healing. An in vitro / in vivo correlation for dressings based on hydrophilic and amphiphilic systems

摘要

Biologic-synthetic dressings based on bilayered systems formed by a synthetic polymer as the external layer and a bioactive and biologically derived material as the internal layer are excellent approaches for the treatment of compromised wounds in the human body.. This work deals with the behaviour of a biodegradable bi-layered wound dressing based polyester-urethanes (PEUR) containing polyethyleneglycol (PEG) or Pluronic F127 coupled to poly(ε-caprolactone) as external layer and a gelatine (G) hydrogel as internal bioactive layer. The G layer was cultivated with dental pulp stem cells (DSPC) before the implantation in a dermal defect of rats. Three types of PEURs were obtained containing PEG of Mn 1000 or 10000, or Pluronic F127, which were labelled PEUR-1, PEUR-10 and PEUR-F127 respectively. PEUR membranes were obtained by the solvent casting method. G hydrogels were prepared from G aqueous solutions (3 wt-%) in the presence of genipin (GP) (5 wt-%) at room temperature for 48 h. The systems were characterized by 1H-NMR, ATR-FTIR, SEC, SEM, DSC, TGA, DMTA and microindentation assays. Swelling and stability behaviour was studied in vitro. Cellular behaviour was evaluated with human fibroblasts and HUVEC through MTT and Alamar Blue assays. Finally in vivo experiments were performed on wounds experimentally created on the back of Wistar rats by the application of the bilayered dressings without cells or with the gelatine layer cultivated previously with DPSC. Chemical composition and crosslinking/stabilization of the G layer were determined by spectroscopic techniques (NMR, FTIR) giving an accurate information of the structure of the bilayered systems as well as the stabilization of the G internal layer. After crosslinking DPSC were seeded into the gel of gelatine. Swelling of PEURs was between 6 and 10% whereas that of G hydrogel was 274%. All samples were not cytotoxic in a standard MTT test. In vivo results after 4 weeks of implantation showed that both PEUR/G hydroge! systems implanted with and without DPSC promotes wound healing. PEUR/G system implanted in the dermis of rats The bilayered PEUR/G systems are effective tissue-engineered constructs that promote the healing of full-thickness skin lesions. With the support of further clinical trials, this procedure could be an alternative to wound healing for patients with partial- and full-thickness burns offering a treatment at a moderate cost and good beneficial in the compromised healing processes.