Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model

Abstract

In recent years, studies have explored novel approaches for cell transplantation to enable annulus fibrosus (AF) regeneration of the intervertebral disc in particular for lumbar disc herniation. Nevertheless, successful engraftment of cells is structurally challenging, and no definitive method has yet been established. This study investigated the potential of cell sheet technology to facilitate cell engraftment for AF repair. AF injury was induced by a 1 × 1 mm defect in rat tails after which AF cell sheets were transplanted. Its regenerative effects were compared to a nondegenerated and degeneration only conditions. Degenerative changes of the entire intervertebral disc were examined by disc height measurements, histology, and immunohistochemistry for 4‐, 8‐, and 12‐weeks post‐transplantation. Cell engraftment was confirmed by tracing PKH26 fluorescent dyed AF cells. In the transplant group, disc degeneration was significantly suppressed after 4, 8, and 12 weeks when compared with the degenerative group, as indicated by histological scoring and DHI observations. At 2 and 4 weeks after transplant, PKH26 positive cells could be detected in defect region and surrounding AF. The results suggest cell engraftment into AF tissue could be established by the cell sheet technology without additional scaffolding or adhesives. In short, AF cell sheets appear to be an effective and accessible tool for AF repair and to support intervertebral disc regeneration.

Mechanical and biological characterization of a composite annulus fibrosus repair strategy in an endplate delamination model

“…Many studies have recorded disc height loss after AF injury, and disc height is considered a benchmark for both degeneration and success of the repair strategy clinically 55 . The results in this study are in agreement with multiple studies that have shown successful repair of the injuries to the central AF in vivo 18,23,27‐29 . Both in terms of significant height loss in injured IVDs and disc height restoration and improvement due to repair.…”

“…55 The results in this study are in agreement with multiple studies that have shown successful repair of the injuries to the central AF in vivo. 18,23,[27][28][29] Both in terms of significant height loss in injured IVDs and disc height restoration and improvement due to repair. These studies were done on small animal models, where the size of the defect is smaller and biomechanical requirements on the repair construct are much lower than in large animals.…”

“…The second class of strategies applies tissue-engineering principles to replace the injured AF with cell-laden scaffolds [25][26][27][28] or cell sheets. 29 To repair the ruptured disc, a system that is biologically and biomechanically compatible must be chosen. Considering the inherent properties of the AF, mechanical design criteria that will allow for restoration of the original mechanical properties can be defined.…”

“…The fillers have also been enhanced with a retention scaffold on the IVD surface 22‐24 to further reinforce the injury site. The second class of strategies applies tissue‐engineering principles to replace the injured AF with cell‐laden scaffolds 25‐28 or cell sheets 29 . While the cell strategies show promising biomechanical results in small animals, as well as cell survival and proliferation, the main aim of accelerating regeneration of the injury by the addition of live cells has had limited evidence of efficacy.…”

Bioadhesives for musculoskeletal tissue regeneration

“…Besides the physical support, bioadhesives have been evolved to deliver bioactive cues and/or cells in addition to provide tissue adhesion [13,14,[17][18][19]. Bioadhesives applied on injured site can serve as effective localized delivery vehicles as secured in situ [13,14,[17][18][19] or providing physical and/or biochemical environment promoting tissue repair [20,21]. Recent improvements in the design and synthesis of bioadhesives have made steps closer to successful applications for musculoskeletal tissues in high mechanical demand.…”