Cell Sheet Technology: An Emerging Approach for Tendon and Ligament Tissue Engineering

Tendon and ligament injuries account for a substantial proportion of disorders in the musculoskeletal system. While non-operative and operative treatment strategies have advanced, the restoration of native tendon and ligament structures after injury is still challenging due to its innate limited regenerative ability. Cell sheet technology is an innovative tool for tissue fabrication and cell transplantation in regenerative medicine. In this review, we first summarize different harvesting procedures and advantages of cell sheet technology, which preserves intact cell-to-cell connections and extracellular matrix. We then describe the recent progress of cell sheet technology from preclinical studies, focusing on the application of stem cell-derived sheets in treating tendon and ligament injuries, as well as highlighting its effects on mitigating inflammation and promoting tendon/graft-bone interface healing. Finally, we discuss several prerequisites for future clinical translation including the selection of appropriate cell source, optimization of preparation process, establishment of suitable animal model, and the fabrication of vascularized complex tissue. We believe this review could potentially provoke new ideas and drive the development of more functional biomimetic tissues using cell sheet technology to meet the needs of clinical patients.