DeFail Alicia J, Chu Constance R, Izzo Nicholas, Marra Kacey G
Department of Bioengineering, University of Pittsburgh, 200 Lothrop Street, BST 1555W, Pittsburgh, PA 15261, USA.
Biomaterials. 2006 Mar;27(8):1579-85. doi: 10.1016/j.biomaterials.2005.08.013. Epub 2005 Sep 6.
Transforming growth factor-beta1 (TGF-beta1) is of great relevance to cartilage development and regeneration. A delivery system for controlled release of growth factors such as TGF-beta1 may be therapeutic for cartilage repair. We have encapsulated TGF-beta1 into poly(DL-lactide-co-glycolide) (PLGA) microspheres, and subsequently incorporated the microspheres into biodegradable hydrogels. The hydrogels are poly(ethylene glycol) based, and the degradation rate of the hydrogels is controlled by the non-toxic cross-linking reagent, genipin. Release kinetics of TGF-beta1 were assessed using ELISA and the bioactivity of the released TGF-beta1 was evaluated using a mink lung cell growth inhibition assay. The controlled release of TGF-beta1 encapsulated within microspheres embedded in scaffolds is better controlled when compared to delivery from microspheres alone. ELISA results indicated that TGF-beta1 was released over 21 days from the delivery system, and the burst release was decreased when the microspheres were embedded in the hydrogels. The concentration of TGF-beta1 released from the gels can be controlled by both the mass of microspheres embedded in the gel, and by the concentration of genipin. Additionally, the scaffold permits containment and conformation of the spheres to the defect shape. Based on these in vitro observations, we predict that we can develop a microsphere-loaded hydrogel for controlled release of TGF-beta1 to a cartilage wound site.
转化生长因子-β1（TGF-β1）与软骨发育和再生密切相关。一种用于控制释放诸如TGF-β1等生长因子的递送系统可能对软骨修复具有治疗作用。我们已将TGF-β1封装到聚（DL-丙交酯-共-乙交酯）（PLGA）微球中，随后将这些微球掺入可生物降解的水凝胶中。这些水凝胶以聚乙二醇为基础，其降解速率由无毒交联剂京尼平控制。使用酶联免疫吸附测定（ELISA）评估TGF-β1的释放动力学，并使用貂肺细胞生长抑制试验评估释放的TGF-β1的生物活性。与单独从微球递送相比，封装在嵌入支架中的微球内的TGF-β1的控释效果更好。ELISA结果表明，TGF-β1从递送系统中释放超过21天，并且当微球嵌入水凝胶中时突释减少。从凝胶中释放的TGF-β1的浓度可以通过嵌入凝胶中的微球质量和京尼平浓度来控制。此外，支架允许微球容纳并适应缺损形状。基于这些体外观察结果，我们预测我们可以开发一种负载微球的水凝胶，用于将TGF-β1控释到软骨伤口部位。
