Tissue engineering strategies from regional functional units to integrated functional reconstruction for intervertebral disc regeneration

Intervertebral disc degeneration (IVDD) is essentially a process of progressive destabilization of the continuous functional system of the intervertebral disc (IVD), which is formed by the nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP). As distinct but interdependent regional functional units, the NP, AF, and CEP jointly maintain disc hydration, mechanical coordination, nutrient supply, and microenvironmental homeostasis. Local tissue degeneration not only disrupts regional function within the IVD but also promotes damage propagation across the disc through structural imbalance and microenvironmental deterioration. With a deeper understanding of regional heterogeneity and functional coupling within the IVD, tissue engineering strategies have evolved from simple tissue replacement toward regenerative approaches that integrate biological features, mechanical requirements, and microenvironmental regulation. According to the distinct tissue morphology, mechanical function, and pathological changes of the NP, AF, and CEP, various therapeutic strategies have been developed for different regions. These strategies provide a crucial foundation for local tissue repair and serve as functional modules that can be further integrated for whole-disc reconstruction. Building on these advances, recent research has increasingly shifted toward multi-region combined repair. Because restoration of disc function depends not on the independent regeneration of a single region, but on coordinated coupling among different regional functional units, integrated strategies place greater emphasis on interfacial continuity, coordinated load transfer, and long-term metabolic support. This review systematically summarizes tissue engineering strategies from regional functional units to integrated functional reconstruction for IVD regeneration, aiming to guide the development of more durable, stable, and function-oriented regenerative therapies for IVDD. The translational potential of this article This review provides a clinically oriented framework for translating intervertebral disc (IVD) tissue engineering from region-specific repair toward integrated functional reconstruction. By linking the distinct biological and mechanical requirements of the nucleus pulposus, annulus fibrosus, and cartilaginous endplate with multi-region and whole-IVD strategies, it identifies design principles relevant to patient-specific regenerative therapy. Particular emphasis is placed on therapeutic cell selection, biomaterial functionality, interfacial integration, nutrient transport, mechanical durability, and microenvironmental regulation. The review also highlights key barriers to clinical translation, including human-scale construct fabrication, limited nutrient supply, long-term mechanical failure, manufacturing reproducibility, regulatory complexity, immunogenicity, cost, and safety. By integrating recent preclinical, large-animal, and emerging clinical evidence, this work may help guide the development and evaluation of more durable, scalable, and clinically applicable regenerative strategies for IVDD, while supporting rational progression from experimental proof-of-concept studies toward clinically relevant therapeutic platforms.