Release kinetics of transforming growth factor-beta1 from fibrin clots.
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.
Giannoni
Paolo
P
ITI Research Institute for Dental and Skeletal Biology, University of Bern, Murtenstrasse 35, P.O. Box 54, CH-3010 Bern, Switzerland.
Hunziker
Ernst B
EB
D000327:Adsorption; D001777:Blood Coagulation / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology; D004058:Diffusion; D004343:Drug Implants / Q000737:chemistry*; D005109:Extracellular Matrix / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry*; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D046911:Macromolecular Substances; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000502:physiology; D053773:Transforming Growth Factor beta1
D004343:Drug Implants; D008081:Liposomes; D046911:Macromolecular Substances; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005337:Fibrin