Ultra-purified alginate gel implantation decreases inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy

Abstract

Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.

A tough nitric oxide-eluting hydrogel coating suppresses neointimal hyperplasia on vascular stent

“…The mild inflammatory response in the group of blank hydrogel plus GSNO was likely to be elicited by gelatin since it was derived from animal tissues that might contain proinflammatory substances 39 , yet the mechanism is not understood. In contrast, alginate might function as an anti-inflammatory mediator 40 so that the degree of inflammation was constrained. Encouragingly, NO molecules generated from the NOE hydrogel contributed extra anti-inflammatory modulation since a number of anti-inflammatory genes such as DUSP5 41 and NRG1 42 were exclusively upregulated (Fig.…”

A Novel Orthotopic Liver Cancer Model for Creating a Human-like Tumor Microenvironment

“…Further research into the mechanism of UPAL gel might be important in future work. Some reports have shown that UPAL gel can suppress interleukin-6 (IL-6) production in rabbit discectomy models [47]. IL-6 is generally known to be one of the major critical cytokines in the TME, promoting tumor proliferation and differentiation [48,49].…”

Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration

“…Recent studies have demonstrated that cell transplantation and biomaterials could potentially be used to treat IVD degeneration. 2 , 3 , 4 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 The transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) into IVDs has shown promise for the treatment of chronic lower back pain. 10 However, BMSC transplantation has several limitations.…”

“… 2 , 15 To date, no biomaterials have been clinically approved for this purpose because each biomaterial did not meet criteria for both biologic and mechanical safety. We had previously developed an original, acellular, bioresorbable, ultra-purified alginate (UPAL) gel to repair IVD degeneration in small 2 , 3 , 15 , 16 and large animal models in vivo . 3 Alginate is a polysaccharide derived from brown seaweed, Phaeophyceae , and exhibits low-level endotoxicity (1/10,000 th that of commercially available laboratory alginate), and thus precludes immunologic reactions.…”

“… 2 , 3 Notably, most animal models of IVD degeneration were created using healthy IVDs and therefore might exhibit natural healing capabilities. 3 , 4 , 8 , 11 , 12 , 13 , 14 , 16 To identify the course of post-surgical IVD degeneration from the onset, we generated a rabbit model of IVD degeneration. 2 , 15 We demonstrated that following discectomy, the use of UPAL gel alone suppressed IVD degeneration compared to the extent of degeneration without UPAL gel treatment.…”