Mechanically conditioned multilayered angle-ply collagen scaffolds promote annulus fibrosus regeneration

Annulus fibrosus (AF) injury, as a result of intervertebral disk degeneration (IVDD) or herniation, is very difficult to heal due to its avascular characteristics. Tissue engineering strategies have become increasingly promising to treat IVDD. However, in light of the fact that AF displays an anisotropic microstructure that results in gradient mechanical properties, fabrication of tissue engineered AF remains challenging. In this study, we fabricated micropatterned collagen scaffolds with angle-ply structure mimicking the microstructural features of AF. Following that, we cultured bone marrow mesenchymal stromal cells (BMSCs) in the scaffolds and applied cyclic stretching to them to mechanically stimulate the cells. We found that aligned cells under mechanical loading showed elevated expression of matrix anabolism-related genes and proteins. Further studies indicated that Caveolin-1 (CAV1) might mediate the nuclear translocation of Yes-associated protein (YAP) in response to external mechanical cues of microgroove-patterned membranes and mechanical loading. Micropatterned collagen membranes, with cells aligning at +/- 30 degrees along the longitudinal dimension, were rolled up together to form an angle-ply and multilayered tissue. After being implanted into the caudal vertebra in a rat model for 4 weeks, biomimetic tissues showed improved restoration of the disk. In general, our biomimetic collagen membranes exhibit great potential in terms of AF regeneration, with AF-like heterogeneous microstructures that satisfy the biomechanical property of the native disk.

Automated summary

In this study, micropatterned collagen scaffolds were fabricated to mimic the microstructural features of annulus fibrosus (AF) and mechanically stimulate bone marrow mesenchymal stromal cells (BMSCs). The aligned cells showed enhanced expression of matrix anabolism-related genes and proteins under mechanical loading. Furthermore, Caveolin-1 (CAV1) was found to mediate the nuclear translocation of Yes-associated protein (YAP) in response to external mechanical cues. The biomimetic collagen membranes formed angle-ply and multilayered tissues that showed improved restoration of the disc in a rat model.