Integrated gradient tissue-engineered osteochondral scaffolds: Challenges, current efforts and future perspectives.

The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis. Tissue engineering has been proposed as a promising strategy to meet the demand of simultaneous regeneration of both cartilage and subchondral bone by constructing integrated gradient tissue-engineered osteochondral scaffold (IGTEOS). This review brought forward the main challenges of establishing a satisfactory IGTEOS from the perspectives of the complexity of physiology and microenvironment of osteochondral tissue, and the limitations of obtaining the desired and required scaffold. Then, we comprehensively discussed and summarized the current tissue-engineered efforts to resolve the above challenges, including architecture strategies, fabrication techniques and in vitro/in vivo evaluation methods of the IGTEOS. Especially, we highlighted the advantages and limitations of various fabrication techniques of IGTEOS, and common cases of IGTEOS application. Finally, based on the above challenges and current research progress, we analyzed in details the future perspectives of tissue-engineered osteochondral construct, so as to achieve the perfect reconstruction of the cartilaginous and osseous layers of osteochondral tissue simultaneously. This comprehensive and instructive review could provide deep insights into our current understanding of IGTEOS.