Modular Tissue Assembly Strategies for Biofabrication of Engineered Cartilage

This review describes the prospects of applying modular assembly techniques and strategies for fabrication of advanced tissue engineered cartilage constructs. Articular cartilage is a tissue that has important functions in preserving and enabling locomotion. However, its limited intrinsic repair capacity and lack of current long-term clinical solutions makes it a candidate for repair or regeneration via tissue engineering strategies. Key advances in biofabrication and 3D bioprinting techniques allowing the specific placement of cells and tissues enable novel strategies to be adopted with increased chances of success. In particular, modular assembly, where separate biological components such as microtissue units, cellular building blocks or spheroids are combined with structural scaffold components to create a functional whole, offers potential as a new strategy for engineering of articular cartilage. Various modular assembly or bottom-up fabrication strategies have been investigated or applied for engineering of a range of tissues and cell types, however, modular approaches to cartilage engineering have been limited thus far. The integrative nature of many current approaches to engineering of articular cartilage means optimization of separate components (such as the scaffold and cells) is challenging, resulting in strategies which are less amenable to clinical scale-up or modification. In addition, current tissue engineering strategies may not replicate the function and complex structure of native tissue. This review outlines recent developments in fabrication of cellular or tissue modules as well as scaffold design where it impacts modular biofabrication, and discusses existing modular approaches applicable to articular cartilage regeneration and repair. Modular tissue assembly approaches allow complex hybrid constructs to be fabricated with direct control over both structural and cellular organization of pre-formed tissue units. The combination of modular assembly with automated biofabrication technologies may offer solutions to the development of optimal tissue-engineered cartilage constructs.