A5: Cell & Molecular Mechanobiology I

ANNULUS FIBROSUS REGENERATION: A LAYER-BY-LAYER ASSEMBLY AND MULTI-MODE MECHANOMODULATION BASED STRATEGY

Bin Li1, Pinghui Zhou, Caihong Zhu, Qianping Guo, Feng Ling, Jibao He

1Soochow University, China

Degenerative disc disease (DDD) is the leading cause of low back pain, a serious global health problem which contributes to healthcare costs significantly. While it is promising to repair degenerated intervertebral discs (IVDs) using tissue engineering techniques, such an approach largely relies on the effective construction of annulus fibrosus (AF), a major load-bearing component of IVD. However, because of the tremendous cellular, biochemical, microstructural, and biomechanical heterogeneity of AF tissue, it remains challenging to fabricate AF replacements that are biologically and functionally comparable to native AF tissue. Recently, we started to employ a tissue engineering strategy based upon layer-by-layer assembly and multi-mode mechanomodulation in order to mimic the layered structure and to address the heterogeneity feature of AF tissue as well. In brief, we isolated multipotent AFderived stem cells (AFSCs) for AF tissue engineering. We then synthesized a series of biodegradable polyurethanes and hydrogels with similar elastic modulus as AF tissue. We found that the biochemical and biomechanical profiles of AFSCs were markedly affected by the elastic modulus of scaffolds, implying the feasibility to induce differentiation of AFSCs into cells at different regions of native AF tissue. We also obtained AFSC sheets, i.e., cell monolayers together with the underlying matrix, using novel cell sheet culture techniques. Further, we applied dynamic mechanical stimulation to AFSCs and found that their anabolic and catabolic metabolisms were significantly dependent on the magnitude, frequency and duration of mechanical stimulation. Following these, we will assembly engineered AF tissue, through a layerby-layer approach, using AFSC sheets primed with substrates of various elasticity and conditioned with appropriate mechanical stimulation. Findings from these studies may provide new insights toward developing engineered AFs whose biological features and mechanical functions approximate those of native AF tissue

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