Breaking the degenerative triad: Microenvironment reprogramming biomaterials for intervertebral disc regeneration
7 affiliations
- 1Department of Chinese Medicine, Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University, Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research, Cangzhou, 061000, China
- 2Department of Orthopaedics, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu CM Clinical Innovation Center of Degenerative Bone and Joint Disease, Wuxi, 214000, China
- 3Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
- 4Department of Chinese Medicine, Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University, Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research, Cangzhou, 061000, China; Corresponding authors.
- 5Department of Rehabilitation, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230000, China; Corresponding author. Department of Rehabilitation, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230000, China.
- 6Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, 050051, China; Corresponding authors. Department of Orthopaedics, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, 050051, China.
- 7Department of Orthopaedics, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu CM Clinical Innovation Center of Degenerative Bone and Joint Disease, Wuxi, 214000, China; Corresponding author.
Abstract
Intervertebral disc degeneration (IVDD) represents a leading cause of chronic low back pain worldwide, imposing considerable public health and socioeconomic burdens. Current clinical interventions remain largely palliative, unable to reverse the progressive pathological cascade. This cascade is driven by a core self-amplifying triad of oxidative stress, chronic inflammation, and nutrient deprivation within the unique avascular, high-load disc niche, and ultimately progresses to end-stage terminal phenotypes such as biomechanical failure and neurovascular ingrowth. Over recent years, biomaterial-based regenerative strategies have evolved from passive structural fillers toward multifunctional platforms capable of active microenvironmental reprogramming. This review provides a systematic, critical synthesis of state-of-the-art advances in the field, organized within a hierarchical framework spanning immunometabolic modulation of the degenerative niche and targeted delivery of cellular and molecular therapeutics with further elaboration of precision-stratified design and whole-disc tissue engineering. We critically appraise evidence maturity across different strategy classes and dissect disc-specific translational barriers, noting that most candidate platforms remain at preclinical validation stages. Building on this analysis, we outline priority research directions and realistic near-term translational milestones to guide rational development of next-generation regenerative platforms toward durable functional disc repair.
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BibTeX
@article{zhao2026breaking,
title = {{Breaking the degenerative triad: Microenvironment reprogramming biomaterials for intervertebral disc regeneration}},
author = {Xuequan Zhao and Xixi Han and Zhuoyi Hu and Yu Chen and Xiwen Wang and Qinglei Liu and Xueliang Hu and Qiang Zhang and Jiaojiao Yue and Yanhao Ge and Yaying Ma and Yixuan Li and Zhongyong Zhang and Fei Li and Wei Chen and Yafeng Zhang},
journal = {Bioactive Materials},
year = {2026},
month = oct,
doi = {10.1016/j.bioactmat.2026.10.026},
url = {https://doi.org/10.1016/j.bioactmat.2026.10.026},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Breaking the degenerative triad: Microenvironment reprogramming biomaterials for intervertebral disc regeneration
AU - Xuequan Zhao
AU - Xixi Han
AU - Zhuoyi Hu
AU - Yu Chen
AU - Xiwen Wang
AU - Qinglei Liu
AU - Xueliang Hu
AU - Qiang Zhang
AU - Jiaojiao Yue
AU - Yanhao Ge
AU - Yaying Ma
AU - Yixuan Li
AU - Zhongyong Zhang
AU - Fei Li
AU - Wei Chen
AU - Yafeng Zhang
PY - 2026
DA - 2026/10/23
JO - Bioactive Materials
DO - 10.1016/j.bioactmat.2026.10.026
UR - https://doi.org/10.1016/j.bioactmat.2026.10.026
AB - Intervertebral disc degeneration (IVDD) represents a leading cause of chronic low back pain worldwide, imposing considerable public health and socioeconomic burdens. Current clinical interventions remain largely palliative, unable to reverse the progressive pathological cascade. This cascade is driven by a core self-amplifying triad of oxidative stress, chronic inflammation, and nutrient deprivation within the unique avascular, high-load disc niche, and ultimately progresses to end-stage terminal phenotypes such as biomechanical failure and neurovascular ingrowth. Over recent years, biomaterial-based regenerative strategies have evolved from passive structural fillers toward multifunctional platforms capable of active microenvironmental reprogramming. This review provides a systematic, critical synthesis of state-of-the-art advances in the field, organized within a hierarchical framework spanning immunometabolic modulation of the degenerative niche and targeted delivery of cellular and molecular therapeutics with further elaboration of precision-stratified design and whole-disc tissue engineering. We critically appraise evidence maturity across different strategy classes and dissect disc-specific translational barriers, noting that most candidate platforms remain at preclinical validation stages. Building on this analysis, we outline priority research directions and realistic near-term translational milestones to guide rational development of next-generation regenerative platforms toward durable functional disc repair.
SN - 2452-199X
ER -