Integrated Mechanobiological Framework for Intervertebral Disc Regeneration: Synergizing Traction-Induced Decompression, Converse Piezoelectricity, and Iontophoretic Substrate Delivery

Background Intervertebral disc (IVD) degeneration is a leading cause of chronic low back pain and disability worldwide. Current conservative interventions—including transcutaneous electrical nerve stimulation (TENS) and mechanical traction—are regarded primarily as symptomatic treatments, with no established mechanism for genuine disc regeneration. Hypothesis This paper proposes a novel mechanistic hypothesis comprising two synergistic components delivered as a single unified protocol. First, spinal traction induces vertebral distraction, reducing intradiscal pressure to sub-atmospheric levels and creating a relative vacuum within the nucleus pulposus; this decompression is hypothesised to relieve compressive inhibition of resident disc progenitor cells—including Tie2+ nucleus pulposus progenitors, notochordal remnant cells, and NP-MSCs—and to enhance endplate diffusion of nutrients and biosynthetic substrates. Second, alternating electrical fields generated by interferential current (IFC) penetrate to disc depth and induce converse piezoelectric effect in the collagen-rich annulus fibrosus, producing nanoscale mechanical oscillations that activate mechanosensitive Piezo1 and Piezo2 ion channels on these resident progenitor cells. The iontophoretic mobility of glucosamine (cationic) and hyaluronic acid (HA; anionic) is exploited during IFC/TENS application to reduce electrode–skin impedance and to deliver chondrogenic substrates transdermally to periannular tissue: HA lowers skin impedance through its hygroscopic and ionic conductivity properties, improving field penetration, while glucosamine provides a direct biosynthetic precursor for glycosaminoglycan synthesis. Traction, IFC, iontophoresis, systemic hydration, and HA gel electrode coupling are co-administered concurrently as inseparable components of a single integrated protocol. Significance Each individual link in this mechanistic chain—traction-induced decompression, collagen piezoelectricity, Piezo channel mechanosensing, iontophoretic drug mobility, impedance-lowering biopolymers, electrical promotion of chondrogenesis, and traction-mediated diffusion enhancement—has independent experimental support. The integrated hypothesis has not been explicitly tested. If validated, this framework would reposition existing, widely available, low-cost physical therapies as genuine biological regenerative interventions, with profound implications for the non-surgical management of disc degeneration. Declaration of Generative AI and AI-Assisted Technologies in the Manuscript Preparation Process During the preparation of this work, the author utilized generative AI infrastructure, specifically Claude (Anthropic, San Francisco, CA) and Gemini (Google, Mountain View, CA), in order to assist with literature synthesis, mathematical formalization, and manuscript structural layouts. After utilizing these tools, the author meticulously reviewed, verified, and edited the contents to meet international academic standards, and takes full responsibility for the final content of the published article.