Department of Plastic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Chin Med J (Engl). 2011 Jan;124(2):284-90.
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.
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.
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.
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.
包膜挛缩已成为与乳房植入物相关的最常见并发症。转化生长因子-β（TGF-β）在纤维性疾病中具有重要作用。由于 TGF-β 在包膜形成发病机制中的关键作用，我们利用温敏 C/GP 水凝胶来控制释放 TGF-β 受体激酶抑制剂（SD208），并研究其对包膜挛缩的影响。
体外降解和 C/GP 水凝胶的药物释放。24 只兔子接受皮下植入物，植入 30ml 光滑硅胶植入物，并随机分为四组：第 1 组接受生理盐水；第 2 组接受 SD208；第 3 组接受 SD208-C/GP；第 4 组接受 C/GP。8 周后，对包膜组织样本进行苏木精和伊红及免疫组织化学染色分析。通过 RT-PCR 检测胶原蛋白 III 和 TGF-β1 的 mRNA 表达。
C/GP 水凝胶可用作理想的药物输送载体，支持 SD208 的控释。SD208-C/GP 治疗组显示包膜厚度显著降低，血管较少。组织学发现证实 SD208-C/GP 组中炎症细胞和纤维母细胞浸润较少。相比之下，在对照组中形成了具有更多血管优势的典型包膜。我们没有观察到 SD208 或 C/GP 治疗对包膜挛缩的相同抑制作用。此外，SD208-C/GP 治疗导致胶原蛋白 III 和 TGF-β1 mRNA 表达明显下调。
本研究表明，温敏 C/GP 水凝胶中 TGF-β 受体激酶抑制剂的控释可显著预防乳房植入物后包膜形成。
