Synthesis and in vivo integration of improved concentrated collagen hydrogels

Normal collagen hydrogels, currently used as the dermal layer of skin substitute Apligraf®, are obtained by encapsulating dermal fibroblasts in a collagen hydrogel at low concentration (0.66 mg/ml). However they suffer from extensive contraction by cells and weak resistance against degradation, which limits their use as permanent graft. We have previously shown that concentrated collagen hydrogels at 3 mg/ml exhibit an improved performance in this respect but nevertheless degrade in vivo to ca. 50% of their initial area after 1 month. We have now investigated a new procedure to synthesize more concentrated collagen hydrogels at 5 mg/ml in order to improve hydrogel resistance and integration capability. The constructs were implanted in subcutaneous pockets in a rat model and analysed after 15 and 30 days. They were still visible after 1 month without any reduction of their area. Histological analysis revealed rapid colonization of the implants by host cells. Neovascularization was observed and reached the core of the implant at day 15. Moreover, cell colonization was not associated with a severe host response. The absence of apoptotic cells evidenced cell viability and the neosynthesis of collagen III a remodelling process. These novel non-crosslinked and cost-effective materials show superior stability and in vivo integration compared to less concentrated collagen hydrogels and appear promising for the treatment of skin lesions.