title: Controlled release of transforming growth factor-beta receptor kinase inhibitor from thermosensitive Chitosan-based hydrogel: application for prevention of capsular contracture.
abstract: 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 follows: 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.
authors.affiliation: Department of Plastic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Diao
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Fu
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Nie
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Hao
authors.forename: Da-Ping
authors.initials: DP
authors.lastname: Yang
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D000818:Animals; D019928:Breast Implantation / Q000009:adverse effects*; D048271:Chitosan / Q000737:chemistry*; D005994:Glycerophosphates / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007150:Immunohistochemistry; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D011817:Rabbits; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005994:Glycerophosphates; D047428:Protein Kinase Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan; C031463:beta-glycerophosphoric acid