Progress of microfluidic hydrogel-based scaffolds and organ-on-chips for the cartilage tissue engineering

Cartilage degeneration is among the fundamental reasons behind disability and pain across the globe. Numerous approaches have been employed to treat cartilage diseases. Nevertheless, none have shown acceptable outcomes in the long run. In this regard, the convergence of tissue engineering and microfabrication principles can allow developing more advanced microfluidic technologies, thus offering attractive alternatives to current treatments and traditional constructs that have been used in tissue engineering applications. Herein, the current developments involving microfluidic hydrogel-based scaffolds, promising structures for cartilage regeneration, ranging from hydrogels with microfluidic channels to hydrogels prepared by the microfluidic devices, that enable therapeutic delivery of cells, drugs, and growth factors, as well as cartilage-related organ-on-chips are reviewed. Thereafter, cartilage anatomy and types of damage, and present treatment options are briefly overviewed. The various types of hydrogels are introduced, and the advantages of microfluidic hydrogel-based scaffolds and hydrogel-based microfluidic platforms over traditional hydrogels are thoroughly discussed. Furthermore, available technologies for fabricating microfluidic hydrogel-based scaffolds and microfluidic chips are presented. The preclinical and clinical applications of microfluidic hydrogel-based scaffolds in cartilage regeneration and the development of cartilage-related microfluidic chips over time are further explained. The current developments, recent key challenges, and attractive prospects that should be considered so as to develop transitional microfluidic systems in cartilage repair are also highlighted and discussed in depth. FGH gratefully acknowledges the support of the Alexander von Humboldt foundation. JMO and RLR thank the funds attributed under the project Health-UNORTE ref. NORTE-01-0145-FEDER000039.