Ogaili Raed H, Alassal Ahmed, Za'aba Nurul Fariha, Zulkiflee Izzat, Mohd Isa Isma Liza
Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, 56000, Kuala Lumpur, Malaysia.
College of Veterinary Medicine, University of Karbala, Karbala, 65001, Iraq.
J Orthop Translat. 2025 Jul 4;53:286-308. doi: 10.1016/j.jot.2025.06.003. eCollection 2025 Jul.
Low back pain (LBP) is a global health problem, primarily caused by intervertebral disc (IVD) degeneration. Current treatments focus on symptom relief without addressing the underlying degenerative mechanisms. Regenerative strategies have emerged as promising therapies through the use of functional biomaterials and stem cells capable of modulating key signalling pathways to promote tissue regeneration. However, challenges such as efficient delivery systems, long-term survival of transplanted cells, and hostile disc microenvironment remain. This review focuses on recent advances in regenerative approaches using biomaterials, cells, and therapeutic agents of exosomes, and genes to restore IVD structure and function. We discuss the current understanding of IVD anatomy, physiology and degeneration pathophysiology followed by current treatments. We highlight the rationale for regenerative therapy in halting the degenerative hallmarks tailored to mild, moderate to severe IVD degeneration. Our review emphasizes on the functional biomaterials designed for advanced delivery system, therapeutic intervention and IVD tissue engineering. We discuss the cell-based therapy, highlighting various cell sources, therapeutic effects, clinical trials and its obstacles. We discuss the use of therapeutic agents such as the genes and exosome therapies in IVD regeneration. The clinical translational potential of regenerative therapy is vast and promising, driven by advances in cellular therapies, biomaterials, and cell-free approaches like exosomes, which offer new avenues for regenerating degenerative IVDs. While significant progress has been made in developing safe, effective, and scalable treatments, challenges remain in immune compatibility, manufacturing, and regulatory pathways. Emerging innovations in gene editing, 3D bioprinting, and personalized approaches are poised to accelerate the translation of these therapies into mainstream medicine, with interdisciplinary collaboration and global efforts playing a crucial role in overcoming current bottlenecks and realizing the full potential of regenerative medicine to transform patient care. This article offers a comprehensive framework to guide preclinical research and future clinical translation of effective regenerative therapies, aiming at reducing the global burden of LBP and improving long-term patient outcomes.
腰痛（LBP）是一个全球性的健康问题，主要由椎间盘（IVD）退变引起。目前的治疗主要集中在缓解症状，而没有解决潜在的退变机制。再生策略已成为有前景的治疗方法，通过使用能够调节关键信号通路以促进组织再生的功能性生物材料和干细胞。然而，诸如高效递送系统、移植细胞的长期存活以及椎间盘恶劣的微环境等挑战仍然存在。本综述重点关注使用生物材料、细胞、外泌体治疗剂和基因来恢复IVD结构和功能的再生方法的最新进展。我们讨论了目前对IVD解剖学、生理学和退变病理生理学的理解，随后介绍了当前的治疗方法。我们强调了再生治疗在阻止针对轻度、中度至重度IVD退变的退变特征方面的基本原理。我们的综述重点介绍了为先进递送系统、治疗干预和IVD组织工程设计的功能性生物材料。我们讨论了基于细胞的治疗方法，重点介绍了各种细胞来源、治疗效果、临床试验及其障碍。我们讨论了在IVD再生中使用基因和外泌体治疗等治疗剂。再生治疗的临床转化潜力巨大且前景广阔，由细胞治疗、生物材料以及外泌体等无细胞方法的进展推动，这些方法为退变IVD的再生提供了新途径。虽然在开发安全、有效且可扩展的治疗方法方面已取得重大进展，但在免疫相容性、制造和监管途径方面仍存在挑战。基因编辑、3D生物打印和个性化方法等新兴创新有望加速这些治疗方法转化为主流医学，跨学科合作和全球努力在克服当前瓶颈以及实现再生医学改善患者护理的全部潜力方面发挥着关键作用。本文提供了一个全面的框架，以指导有效的再生治疗的临床前研究和未来的临床转化，旨在减轻全球LBP负担并改善患者的长期预后。
