An Injectable AAm-DMAEMA/Alg-Ca2⁺ Gel Designed for Damaged Intervertebral Discs Therapy.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain and imposes a significant burden on individuals and society. Bioactive materials are widely used for tissue repair. Here, we designed a calcium alginate (Alg-Ca2⁺) modified with N, N-dimethylaminoethyl methacrylate (DMAEMA) and acrylamide (AAm), named AAm-DMAEMA/Alg-Ca2⁺, and evaluated its effects on IVDD repair. METHODS: Morphology of AAm-DMAEMA/Alg-Ca2⁺ (referred to as AAm) was analyzed by SEM. IVDD was induced in rats via Co6/7 and Co7/8 disc puncture, followed by AAm treatment. Disc height, tissue integrity, and matrix composition were assessed by X-ray, MRI, HE, and Safranin O staining. Aggrecan, collagen I/II, MMP3/13, and Ki-67 were analyzed by immunohistochemistry and immunofluorescence. NP cells exposed to H2O2 were used to model inflammation in vitro; cell viability, proliferation, and inflammatory factor expression were measured by CCK-8, EdU, qPCR, and immunofluorescence (IF) assays. RESULTS: AAm treatment significantly enhanced the viability and proliferation of NP cells by almost 50% percent. AAm treatment notably alleviated disc height loss, restored tissue integrity, and increased the DHI value in rat model. MRI images showed that while the endplate signal was decreased in the model group, AAm treatment increased the signal at 4 and 8 weeks post-modeling. AAm mitigated disc height loss, improved MRI signals, preserved nucleus pulposus structure, reduced fibrous tissue formation, and promoted bone formation and chondrogenesis. AAm treatment repressed the levels of TNF-α, IL-1, IL-6, and NLRP3 in NP cells. H2O2 induction suppressed the levels of Aggrecan and collagen II and elevated MMP3 and MMP13 expression in NP cells, effects that were reversed by the administration of AAm. CONCLUSION: AAm treatment facilitates the proliferation of NP cells, represses the inflammatory response, alleviates tissue damage, and enhances bone formation in IVDD. These results indicate that AAm-DMAEMA/Alg-Ca2+ hydrogel is a promising bioactive scaffold for promoting IVDD.