Computational screening of alginate biomaterials for intervertebral disc repair via agent-based simulation.

BACKGROUND AND OBJECTIVES: Low back pain, driven largely by intervertebral disc (IVD) degeneration within the central nucleus pulposus (NP) region, affects over 600 million people globally. Although hydrogels are promising biomaterials for NP repair, optimizing their interdependent design parameters through traditional experimentation is resource intensive. This study developed an IVD-hydrogel agent-based model (IVDH-ABM) for computational screening of alginate biomaterial formulations. METHODS: The IVDH-ABM was implemented in C++ with OpenMP and CUDA. This lattice-based model simulated 27,000 NP cell agents at 10 µm spatial resolution, with local physical and chemical cues of proliferation, apoptosis, migration, and extracellular matrix secretion over 21 simulated days. Unknown parameters were calibrated with the Nelder-Mead algorithm against empirical data from four alginate hydrogel conditions. Predictions were validated against withheld experimental data for aggrecan accumulation and NP cell viability and against independent literature data for cell fold change, collagen, and cytokine secretion, with agreement quantified by root mean squared error, normalized RMSE, and coverage probability. RESULTS: The IVDH-ABM predicted NP cell proliferation of 8.3- to 9.2-fold by day 16, aggrecan stabilizing at 2700 to 2800 µg/mL in the low molecular weight conditions, and collagen-to-aggrecan ratios within the physiological range of 0.18 to 0.42. Cytokine dynamics tracked the reported literature ranges (normalized RMSE 0.25 to 0.40 for IL-1β and TGF-β). Late cell fold change was over-predicted relative to experimental values. Multi-objective screening identified an optimal formulation of 200 kDa alginate at 1.95% (w/v) crosslinked with 0.02 M calcium. Its predicted elasticity of 3.66 kPa was within the mechanical range of mature, non-degenerate NP tissue. CONCLUSIONS: The IVDH-ABM provides a computational framework for the in-silico screening of hydrogel biomaterials. This New Approach Methodology aligns with the growing emphasis on alternative non-animal methods for regenerative medicine research.