Curcumin-loaded dynamic crosslinked injectable hydrogel for annulus fibrosus repair and disc degeneration prevention

OBJECTIVE: Annulus fibrosus (AF) defects following discectomy often induce biomechanical instability and inflammatory microenvironment deterioration, key drivers of recurrent herniation and accelerated degeneration. Given the limited self-repair capacity of the AF, this study aimed to develop a novel composite hydrogel integrating immediate mechanical support, tissue adhesion, and sustained anti-inflammatory release to promote functional AF repair. METHODS: A composite hydrogel was prepared by incorporating curcumin-loaded liposomes (LIP@CUR) into a Schiff-base-crosslinked network formed between 4-arm polyethylene glycol (4aPEG-OPA) and gelatin. The hydrogel was comprehensively characterized in terms of microstructure, rheological behavior, mechanical properties, degradation profile, and in vitro drug release. Biocompatibility was evaluated using cytotoxicity and hemolysis assays. For in vivo assessment, male Japanese White rabbits (2.5 ± 0.2 kg) were obtained from Wangdu Tonghui Breeding Co., Ltd. (Hebei, China; License No. SCXK (Ji) 2021-006), and an AF defect model was established. Therapeutic efficacy was evaluated by maintaining disc height and by quantifying inflammatory responses (IL-6, TNF-α) and assessing extracellular matrix components (COL I/II) using radiography and histological analyses. RESULTS: LIP@CUR exhibited uniform particle size (159.68 ± 1.98 nm) with ~ 70% encapsulation efficiency. The composite hydrogel demonstrated rapid in situ gelation (~ 60 s) and a compressive modulus (114.06 ± 13.94 kPa) matching native AF tissue, alongside robust tissue adhesion strength (~ 50 kPa). In vitro assessments confirmed low swelling, controllable degradation, and sustained curcumin release without cytotoxicity. In vivo, the hydrogel group effectively maintained intervertebral disc height and improved MRI signal intensity. Histological and semi-quantitative analyses confirmed a significant downregulation of inflammatory cytokines (TNF-α and IL-6, p < 0.001), alongside enhanced collagen deposition, facilitating structural regeneration of the AF defect. CONCLUSION: This study successfully developed a functionalized composite hydrogel featuring dual-controlled release, mechanical compatibility, and anti-inflammatory activity. By synergistically providing physical closure and modulating the immune microenvironment, this material offers a promising clinical strategy for preventing postoperative disc recurrence and enhancing AF repair.