Mechanically and biologically promoted cell-laden constructs generated using tissue-specific bioinks for tendon/ligament tissue engineering applications

Abstract

Tendon and ligament tissues provide stability and mobility crucial for musculoskeletal function, but are particularly prone to injury. Owing to poor innate healing capacity, the regeneration of mature and functional tendon/ligament (T/L) poses a formidable clinical challenge. Advanced bioengineering strategies to develop biomimetic tissue implants are highly desired for the treatment of T/L injuries. Here, we presented a cell-based tissue engineering strategy to generate cell-laden tissue constructs comprising stem cells and tissue-specific bioinks using 3D cell-printing technology. We implemented an in vitro preconditioning approach to guide semi-organized T/L-like formation before the in vivo application of cell-printed implants. During in vitro maturation, tissue-specific decellularized extracellular matrix-based cellular constructs facilitated long-term in vitro culture with high cell viability and promoted tenogenesis with enhanced cellular/structural anisotropy. Moreover, we demonstrated improved cell survival/retention upon in vivo implantation of pre-matured constructs in nude mice with de novo tendon formation and improved mechanical strength. Although in vivo mechanical properties of the cell-printed implants were lower than those of human T/L tissues, the results of this study may have significant implications for future cell-based therapies in tendon and ligament regeneration and translational medicine.