Injectable hydrogels for cartilage and bone tissue engineering

Abstract

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.

Figure 1

Schematic illustration of approaches to make injectable hydrogels for cartilage- and bone tissue-engineering applications.

Figure 2

Schematic illustration of depth-dependent architecture of cartilage tissue. From the superficial zone to the deep zone, the proteoglycan content gradually increases. In the superficial zone, the collagen fibers are aligned parallel to the surface. Collagen fibers in the middle zone are unaligned and tangential to the cartilage surface. In the deep zone, collagen fibers are arranged radially. Finally, the collagen fibers in the calcified zone tend to arborize with little organization and mineralization.

Figure 3

Schematic illustration of a distinct hierarchical structure of bone tissue. (a)At the macrostructural level, bone is composed of cortical bone and cancellous bone. (b) At the microstructural level, the cortical bone is made up of repeated units of osteon, which is characterized by 20–30 concentric layers of collagen fibers, called lamellae. The lamellae surround the central canal and contain various blood vessels and nerves. (c) At the nanostructural level, there are large numbers of collagen fibers, which are composed of periodic collagen fibrils and gaps between the collagen molecules. The calcium phosphate crystals and non-collagenous organic proteins are embedded in these gaps between collagen molecules.

Figure 4

Schematic illustration of injectable hydrogels prepared by the enzymatic cross-linking method with horseradish peroxidase (HRP) and H₂O₂.

Figure 5

Schematic illustration of injectable hydrogels prepared by Schiff base cross-linking between aqueous solutions of GC and poly(EO-co-Gly)-CHO.

Figure 6

Schematic illustration of injectable hydrogels prepared by the Michael addition cross-linking method.

Figure 7

Schematic illustration of injectable hydrogels prepared by click chemistry.

Figure 8

Schematic illustration of injectable hydrogels prepared by the photo-cross-linking method. Reprinted with permission from ref. 2009 Elsevier Publishing Group.