Bioengineered inflammation-sensitive supramolecular β–cyclodextrin–complex embedded in collagen/hyaluronic acid injectable hydrogel for nucleus pulposus regeneration in an intervertebral disc degeneration rat model

作者：Zhen Wang, Jichen Liu, Wei He, Haishan Xu, Yanhua Sun, Xuegang Liang, Shiqing Xu, Bin Hao, Jian Ma, Xijing He · 发表于：International Journal of Biological Macromolecules · 年份：2025 · DOI：10.1016/j.ijbiomac.2025.147585 · 被引用次数：4 · 研究领域：Spine and Intervertebral Disc Pathology、Cancer Treatment and Pharmacology、Plant-based Medicinal Research

Intervertebral disc degeneration (IVDD) is a primary contributor to chronic low back pain, affecting over 500 million people globally. In this study, we engineered an injectable collagen-hyaluronic acid (Col-HA) hydrogel incorporating a β-cyclodextrin-resveratrol (β-CD-RES) supramolecular complex, designed to exhibit inflammation-sensitive drug release and promote nucleus pulposus (NP) regeneration. The hydrogel exhibited rapid gelation (within ∼3 min at 37 °C), high compressive strength (35 kPa), and an extended water retention time of 7 h. Drug release analysis showed a sustained resveratrol release, with 60 % released from β-CD-RES and 40 % from β-CD-RES/Col-HA over 96 h. In vitro, the hydrogel supported enhanced NPC proliferation, maintained >90 % cell viability, and significantly reduced ROS levels and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), indicating effective inflammation-facilitated drug delivery. In vivo, rats treated with β-CD-RES/Col-HA showed a marked improvement in disc height index (DHI%), as well as higher expression of COL-II and aggrecan mRNA after 8 weeks. These findings demonstrate the hydrogel's dual role as a supportive scaffold and targeted therapeutic platform for minimally invasive intervertebral disc regeneration.