Tissue-Engineered Decellularized Allografts for Anterior Cruciate Ligament Reconstruction

Abstract

Anterior cruciate ligament (ACL) reconstruction with allografts is limited by high immunogenicity, poor cellularization, and delayed tendon–bone healing. Decellularized tendons (DAs) have been used as bioscaffolds to reconstruct ligaments with variable success. In the study, four kinds of decellularized allogeneic hamstring tendons were prepared and their microstructure and cytocompatibility were examined in vitro. The results showed that decellularized allografts neutralized by 5% calcium bicarbonate had typical reticular and porous microstructures with optical cytocompatibility. Tissue-engineering decellularized allografts (TEDAs) were prepared with the selected decellularized allografts and tendon stem/progenitor cells and used for ACL reconstruction in a rabbit model. Histological staining showed that the TEDAs promoted cellular infiltration and new vessel formation significantly and improved tendon–bone healing moderately compared to decellularized allografts. Better macroscopic scores and biomechanical results were observed in TEDA groups, but there were no significant differences between DA and TEDA groups at months 1, 2, and 3 postoperatively. Immunohistochemical data showed that the tissue-engineering decellularized allografts enhanced the expression of collagen I at each timepoint and collagen III at months 1 and 2. ELISA analysis showed that the tissue-engineering decellularized allografts reduced the secretion of IgE and IL-1β within 1 month and promoted the secretion of IL-2, IL-4, IL-10, and IL-17 after 1 month. The results showed that tissue-engineering decellularized allografts strengthened intra-articular graft remodeling significantly and provided moderate improvements in tendon–bone healing by creating more suitable immune responses than decellularized allografts. The study revealed that tissue-engineering decellularized allografts as a promising option for ACL reconstruction could achieve more favorable outcomes.

The optimization of pepsin processing time to balance the mechanical and biological properties of xenogeneic bone

“…The calcium nodulus production of cells on different xenogeneic bone scaffolds was semiquantified through a well‐developed method 15 . Briefly, after culturing for 14 days, the xenogeneic bones of different groups were washed with PBS and fixed with PFA (4%, 30 min).…”

Tissue engineering approaches for the repair and regeneration of the anterior cruciate ligament: towards 3D bioprinted ACL-on-chip

“…In a recent study on the decellularisation of allografts, release of IgE and IL-1 at the wound site was considerably lower at the early stage, indicating a decreased immunological response. However, tissue regeneration is likely to require proper inflammatory responses, which may be limited by high levels of proinflammatory cytokine (Li et al, 2020).…”

Tissue Engineering for Mimics and Modulations of Immune Functions

“…[ 92 ] Another candidate for anterior cruciate ligament reconstruction was developed by decellularizing the allogenic hamstring tendon and implanting it together with autologous tendon stem/progenitor cells. [ 97 ] Jeinsen et al. developed an intensified decellularization method for equine carotid arteries by threading onto Teflon tubes before transferring to 0.5% SDS and 0.5% sodium deoxycholate solution for an extended period (72 h) to avoid collapse and promote decellularization, followed by washing in an increased volume of solution.…”