Fibrin for Encapsulation of Human Mesenchymal Stem Cells for Chondrogenic Differentiation

Abstract

Age-related wear and tear of cartilage (osteoarthritis) and traumatic cartilage damage are a leading cause of disability in developed nations. Articular (hyaline) cartilage covers the ends of the bones of synovial joints and is a complex, multilayered structure varying in composition with location in a joint, and in relation to load and shear forces at that specific site. When damaged, articular cartilage tissue does not have the ability to repair itself, but rather is usually replaced by fibrocartilage which does not have suitable compressive properties, leading to breakdown, pain and can ultimately require replacement by prosthetic joint. Thus, cartilage repair remains a clinical challenge and few current treatments yield satisfactory clinical results over the long term. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function, and provides a scientific basis for integrating the proper cell populations, suitable cellular signals and appropriate scaffolds for optimum tissue development and organ replacement strategies. Fibrin has been used as both a delivery vehicle and as a scaffolding matrix for tissue engineering. The emergence of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine is due to their capability to repopulate and differentiate into several tissue lineages, including both cartilage and bone. Human MSCs have been used in combination with a wide range of fibrin scaffolds including both autologous and allogeneic human fibrin glue either as a platelet-rich or normal formulation, in addition to commercially available bovine fibrin hydrogel precursors. This approach permits high density of cells to be implanted, wherein chemical manipulation of the fibrin scaffold modulates its stability, strength and complement of growth factors, while maintaining the promise of an autologous repair solution. This review focuses on recent advances in the application of the fibrinogen/fibrin system for tissue engineering of articular cartilage.