Controlled release of transforming growth factor-beta receptor kinase inhibitor from thermosensitive Chitosan-based hydrogel: Application for prevention of capsular contracture

Background Capsular contracture has become the most common complication associated with breast implant.Transforming growth factor-beta (TGF-β) is well known for a prominent role in fibrotic diseases.Due to the critical role of TGF-β in pathogenesis of capsular formation,we utilized thermosensitive C/GP hydrogel to controlled release of TGF-β receptor kinase inhibitor (SD208) and investigated their effects on capsular contracture.Methods In vitro degradation and drug release of C/GP hydrogel were performed.Twenty-four rabbits underwent subpanniculus implantation with 30 ml smooth silicone implants and were randomly divided into four groups as fellows:Group 1 received saline solution;Group 2 received SD208;Group 3 received SD208-C/GP;Group 4 received C/GP.At 8 weeks,the samples of capsular tissues were analyzed by hematoxylin and eosin and immunohistological staining.The mRNA expression of collagen Ⅲ and TGF-β1 was detected by RT-PCR assay.Results C/GP hydrogel could be applied as an ideal drug delivery vehicle which supported the controlled release of SD208.SD208-C/GP treatment showed a significant reduction in capsule thickness with fewer vessels.The histological findings confirmed that the lower amounts of inflammatory cells and fibroblasts infiltrate in SD208-C/GP group.In contrast,typical capsules with more vessel predominance were developed in control group.We did not observe the same inhibitory effect of SD208 or C/GP treatment on capsular contracture.Moreover,SD208-C/GP therapy yielded an evident down-regulation of collagen Ⅲ and TGF-β1 mRNA expression.Conclusions This study demonstrated that controlled release of TGF-β receptor kinase inhibitor from thermosensitive C/GP hydrogel could significantly prevent capsule formation after mammary implants.