Trans-endplate delivery of arginine-based poly (ester amide) for structure-preserving therapy of intervertebral disc degeneration
7 affiliations
- 1Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- 2Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518057, China
- 3Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
- 4Department of Orthopedics, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital) & Dongguan Key Laboratory of Basic, Clinical and Digital Research on Common Orthopedic Diseases, Dongguan, 523000, China
- 5Department of Spine Surgery, The Affiliated Hospital of Qingdao University, 59# Haier Rd. Qingdao, Shandong, 266000, China
- 6Department of Orthopaedic Surgery Qilu Hospital Cheeloo College of Medicine Shandong University, Jinan, Shandong, 250012, China
- 7Bioscience and Biomedical Engineering Thrust, Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, 511400, China
Abstract
Intervertebral disc degeneration (IDD) remains a major cause of chronic low back pain, yet effective disease-modifying therapies are lacking. Current advanced interventions, including cell-based therapies and matrix supplementation, often disrupt disc structural integrity and fail to achieve sustained regeneration. Here, we rationally designed and synthesized a series of arginine-based poly(ester amide)s (Arg-PEAs) as endplate-penetrating biomaterials for non-direct disc therapy. Unlike conventional intradiscal injection, Arg-PEAs were administered into the adjacent vertebral bodies, enabling trans-endplate delivery into the nucleus pulposus (NP). Among them, the lead polymer 8A6S demonstrated excellent biocompatibility and efficient accumulation within the NP, as confirmed by ex vivo and in vivo imaging. Mechanistically, 8A6S suppressed IL-17 signaling by attenuating TRAF6-mediated NF-κB activation, thereby reducing inflammatory catabolism (MMP13, ADAMTS5) and restoring anabolic extracellular matrix markers (ACAN, COL2A1, SOX9). This re-establishment of matrix homeostasis promoted NP regeneration in both rat and caprine models of IDD. Collectively, this study establishes Arg-PEAs as a new class of bioactive polymers capable of trans-endplate delivery and inflammation-modulating regeneration, providing a minimally invasive and structurally preserving strategy for IDD treatment.
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BibTeX
@article{ling2026transendplate,
title = {{Trans-endplate delivery of arginine-based poly (ester amide) for structure-preserving therapy of intervertebral disc degeneration}},
author = {Zemin Ling and Qilun Guo and Tong Tong and Yanrun Li and Xinru You and Baoyi Jiang and NingNing Chen and Dawei Yuan and Jun Shen and Fu Zhang and Huachuan Wu and Jianwen Li and Songbo Li and Hongfei Xiang and Lei Cheng and Chu Tao and Jun Wu and Fuxin Wei},
journal = {Bioactive materials},
year = {2026},
month = oct,
doi = {10.1016/j.bioactmat.2026.09.039},
url = {https://europepmc.org/article/PMC/PMC13717038},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Trans-endplate delivery of arginine-based poly (ester amide) for structure-preserving therapy of intervertebral disc degeneration
AU - Zemin Ling
AU - Qilun Guo
AU - Tong Tong
AU - Yanrun Li
AU - Xinru You
AU - Baoyi Jiang
AU - NingNing Chen
AU - Dawei Yuan
AU - Jun Shen
AU - Fu Zhang
AU - Huachuan Wu
AU - Jianwen Li
AU - Songbo Li
AU - Hongfei Xiang
AU - Lei Cheng
AU - Chu Tao
AU - Jun Wu
AU - Fuxin Wei
PY - 2026
DA - 2026/10/22
JO - Bioactive materials
DO - 10.1016/j.bioactmat.2026.09.039
UR - https://europepmc.org/article/PMC/PMC13717038
AB - Intervertebral disc degeneration (IDD) remains a major cause of chronic low back pain, yet effective disease-modifying therapies are lacking. Current advanced interventions, including cell-based therapies and matrix supplementation, often disrupt disc structural integrity and fail to achieve sustained regeneration. Here, we rationally designed and synthesized a series of arginine-based poly(ester amide)s (Arg-PEAs) as endplate-penetrating biomaterials for non-direct disc therapy. Unlike conventional intradiscal injection, Arg-PEAs were administered into the adjacent vertebral bodies, enabling trans-endplate delivery into the nucleus pulposus (NP). Among them, the lead polymer 8A6S demonstrated excellent biocompatibility and efficient accumulation within the NP, as confirmed by ex vivo and in vivo imaging. Mechanistically, 8A6S suppressed IL-17 signaling by attenuating TRAF6-mediated NF-κB activation, thereby reducing inflammatory catabolism (MMP13, ADAMTS5) and restoring anabolic extracellular matrix markers (ACAN, COL2A1, SOX9). This re-establishment of matrix homeostasis promoted NP regeneration in both rat and caprine models of IDD. Collectively, this study establishes Arg-PEAs as a new class of bioactive polymers capable of trans-endplate delivery and inflammation-modulating regeneration, providing a minimally invasive and structurally preserving strategy for IDD treatment.
SN - 2452-199X
ER -