STATEMENT OF SIGNIFICANCE: In this study, we developed a silk scaffold with increased stiffness and SDF-1 controlled release capacity for ligament repair. This advanced scaffold transplantation combined with intra-articular injection of LSPCs (which was isolated from rabbit ligament for the first time in this study) promoted the regeneration of both the tendinous and bone tunnel portion of ACL. This therapeutic strategy also ameliorated cartilage degeneration and reduced the severity of arthrofibrosis. Hence, combining LSPCs injection with SDF-1-releasing silk scaffold is demonstrated as a therapeutic strategy for ACL regeneration and OA treatment in the clinic.
METHODS: The decellularization was achieved using a developed closed sonication treatment system for 10 hrs, and continued with a washing process for 5 days. For the control, a simple immersion treatment was set as a benchmark to compare the decellularization efficiency. Histological and biochemical assays were conducted to investigate the cell removal and retention of the vital extracellular matrix. Surface ultrastructure of the prepared scaffolds was evaluated using scanning electron microscope at 5,000× magnification viewed from cross and longitudinal sections. In addition, the biomechanical properties were investigated through ball indentation testing to study the stiffness, residual forces and compression characteristics. Statistical significance between the samples was determined with p-value =0.05.
RESULTS: Histological and biochemical assays confirmed the elimination of antigenic cellular components with the retention of the vital extracellular matrix within the sonicated scaffolds. However, there was a significant removal of sulfated glycosaminoglycans. The surface histoarchitecture portrayed the preserved collagen fibril orientation and arrangement. However, there were minor disruptions on the structure, with few empty micropores formed which represented cell lacunae. The biomechanical properties of bioscaffolds showed the retention of viscoelastic behavior of the scaffolds which mimic native tissues. After immersion treatment, those scaffolds had poor results compared to the sonicated scaffolds due to the inefficiency of the treatment.
CONCLUSION: In conclusion, this study reported that the closed sonication treatment system had high capabilities to prepare ideal bioscaffolds with excellent removal of cellular components, and retained extracellular matrix and biomechanical properties.
METHODS: In this review, we first discussed the anatomy, physiology and pathophysiology of tendon and ligament injuries and its current treatment. Secondly, we explored the current role of tendon and ligament tissue engineering, describing its recent advances. After that, we also described stem cell and cell secreted product approaches in tendon and ligament injuries. Lastly, we examined the role of the bioreactor and mechanical loading in in vitro maturation of engineered tendon and ligament.
RESULTS: Tissue engineering offers various alternative ways of treatment from biological tissue constructs to stem cell therapy and cell secreted products. Bioreactor with mechanical stimulation is instrumental in preparing mature engineered tendon and ligament substitutes in vitro.
CONCLUSIONS: Tissue engineering showed great promise in replacing the damaged tendon and ligament. However, more study is needed to develop ideal engineered tendon and ligament.