Advanced Strategies for Articular Cartilage Defect Repair

Abstract

Articular cartilage is a unique tissue owing to its ability to withstand repetitive compressive stress throughout an individual's lifetime. However, its major limitation is the inability to heal even the most minor injuries. There still remains an inherent lack of strategies that stimulate hyaline-like articular cartilage growth with appropriate functional properties. Recent scientific advances in tissue engineering have made significant steps towards development of constructs for articular cartilage repair. In particular, research has shown the potential of biomaterial physico-chemical properties significantly influencing the proliferation, differentiation and matrix deposition by progenitor cells. Accordingly, this highlights the potential of using such properties to direct the lineage towards which such cells follow. Moreover, the use of soluble growth factors to enhance the bioactivity and regenerative capacity of biomaterials has recently been adopted by researchers in the field of tissue engineering. In addition, gene therapy is a growing area that has found noteworthy use in tissue engineering partly due to the potential to overcome some drawbacks associated with current growth factor delivery systems. In this context, such advanced strategies in biomaterial science, cell-based and growth factor-based therapies that have been employed in the restoration and repair of damaged articular cartilage will be the focus of this review article.

Keywords: articular cartilage; biomaterials; chondrogenesis; scaffolds; tissue engineering.

Figure 1

The structural organization of articular cartilage from the superficial zone to the deep zone and the calcified cartilage. The illustration on the left shows collagen fibers and chondrocytes of articular cartilage demonstrating the difference in their orientation and shape within the different zones. The histological image (haemotoxylin and eosin (H&E) staining) on the right is taken from the femoral condyle of a rabbit knee joint and demonstrates the distribution of chondrocytes within the different zones (scale bar represents 100 µm).

Figure 2

An illustration of the tissue engineering triad comprised of cells, scaffolds and biological signal molecules. (Scaffold scanning electron microscope (SEM) image reprinted with permission from [38]. Copyright 2012 Elsevier).

Figure 3

Scanning electron microscope images of collagen-glycosaminoglycan scaffolds with two distinct mean pore sizes; 94 µm (A); 130 µm (B). The scale bar represents 100 µm.

Figure 4

An illustration of three scaffold characteristics that have a fundamental role in the response of cells. One important property is the microstructure of scaffolds that may influence cell infiltration (central scaffold SEM image reprinted with permission from [38], copyright (2012) Elsevier). Magnified SEM image shows the microstructure of a collagen-based scaffold. The chemical composition is another important property that can alter cell-scaffold adhesion. The chemical structure represents a hyaluronic acid disaccharide unit, n~5000 (Reprinted with permission from [138], copyright 1972 Nature Publishing Group). The mechanical property of the scaffold also plays an important role in cell response by influencing cell proliferation, differentiation and migration (the graph shows a typical stress-strain curve of a ductile material).

Figure 5

Scanning electron microscope image of a collagen scaffold incorporated with alginate micro-particles. The micro-particles can be seen adhered to the struts of the scaffolds. The scale bar represents a 5 µm length.