Release kinetics of transforming growth factor-beta1 from fibrin clots

Biotechnol Bioeng. 2003 Jul 5;83(1):121-3. doi: 10.1002/bit.10639.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Blood Coagulation / physiology
  • Chondrogenesis / physiology
  • Diffusion
  • Drug Implants / chemistry*
  • Extracellular Matrix / chemistry*
  • Fibrin / chemistry*
  • Kinetics
  • Liposomes / chemistry*
  • Macromolecular Substances
  • Tissue Engineering / methods*
  • Transforming Growth Factor beta / chemistry*
  • Transforming Growth Factor beta / physiology
  • Transforming Growth Factor beta1

Substances

  • Drug Implants
  • Liposomes
  • Macromolecular Substances
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Fibrin