Giannoni Paolo, Hunziker Ernst B
ITI Research Institute for Dental and Skeletal Biology, University of Bern, Murtenstrasse 35, P.O. Box 54, CH-3010 Bern, Switzerland.
Biotechnol Bioeng. 2003 Jul 5;83(1):121-3. doi: 10.1002/bit.10639.
In any therapeutic model involving a tissue-engineering approach to the repair of partial-thickness articular cartilage defects, a chondrogenic differentiation factor is required to ensure tissue-specific healing. Transforming growth factor-beta1 (TGF-beta1) is known to act in this capacity, but at such high concentrations as to render its direct injection into the joint cavity inadvisable. This situation calls for a delivery system that can be applied directly to the defect site and that will release the drug gradually over a period of some weeks. Liposome encapsulation represents one such system, and has been recently implemented with some success in an animal model for cartilage repair. However, the kinetics of TGF-beta1 release have not been determined, it was the purpose of the present study to characterize these. The liberation of [(125)I]-labeled TGF-beta1 from fibrin matrices containing this agent in either a free or liposome-encapsulated form was monitored by liquid scintillation counting for 25 days in vitro. During the initial 5 days, fibrin clots containing liposome-encapsulated TGF-beta1 released this cytokine at a slower rate (2% to 4% per day) than did those containing the free molecules (10% to 20% per day); thereafter, the release rates were similar. At the end of the incubation period, only 40% of the liposome-encapsulated TGF-beta1 had been released from the fibrin clots, as compared with 68% from those containing the free molecules. Liposome encapsulation thus represents a suitable means of establishing a slow-delivery system in tissue-engineering approaches to articular cartilage repair.
在任何涉及采用组织工程方法修复部分厚度关节软骨缺损的治疗模型中，都需要一种软骨分化因子来确保组织特异性愈合。已知转化生长因子-β1（TGF-β1）具有此功能，但由于其浓度过高，不宜直接注射到关节腔中。这种情况需要一种可直接应用于缺损部位且能在数周内逐渐释放药物的递送系统。脂质体包封就是这样一种系统，最近在软骨修复的动物模型中已取得了一定成功。然而，TGF-β1的释放动力学尚未确定，本研究的目的就是对其进行表征。通过液体闪烁计数法在体外监测[(125)I]标记的TGF-β1从含有游离或脂质体包封形式该因子的纤维蛋白基质中的释放情况，为期25天。在最初的5天里，含有脂质体包封TGF-β1的纤维蛋白凝块释放这种细胞因子的速度（每天2%至4%）比含有游离分子的凝块（每天10%至20%）慢；此后，释放速率相似。在孵育期结束时，只有40%的脂质体包封TGF-β1从纤维蛋白凝块中释放出来，而含有游离分子的凝块则为68%。因此，脂质体包封是在组织工程方法修复关节软骨中建立缓慢递送系统的一种合适手段。
