Design Principles and Mechanics: A Review of Emerging Paradigms in Intervertebral Disc Regeneration and Replacement

ABSTRACT Low back pain is a leading cause of disability worldwide, imposing a substantial socioeconomic burden, particularly among aging and obese populations. Intervertebral disc degeneration is a major contributor, yet current solutions, like fusion and total disc replacement, fail to fully restore physiological function. Fusion restricts mobility and accelerates adjacent segment degeneration, while current prostheses and replacement devices often lack mechanical fidelity to the native disc. This review highlights the pressing need for next‐generation IVD replacements that replicate both the mechanical behavior and biological functionality of native tissue. We outline the spatially varying mechanical properties of the nucleus pulposus and annulus fibrosus, and examine how current solutions, such as minimally invasive procedures, and artificial constructs, both cellular and acellular, attempt to match these benchmarks. A design framework is presented that links mechanical functional targets with strategies, including region‐specific architecture, multi‐material scaffolds, fiber alignment, and biological functional targets with bioactivity enhancement through cell therapy, gene delivery, exosome therapy, and immunomodulation. Future efforts must prioritize spatial tunability of mechanical properties, mimic those of the native intervertebral disc, and promote biological activity to enhance integration, through upregulation of regenerative signals and suppression of inflammatory pathways.