Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy

Abstract

Surgery is the final choice for most patients with intervertebral disc degeneration (IDD). Operation-caused trauma will cause inflammation in the intervertebral disc. Serious inflammation will cause tissue defects and induce tissue degeneration, IDD recurrence and the occurrence of other diseases. Therefore, we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin (ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local inflammation. ASP-liposomes (ASP-Lips) were incorporated into a photocrosslinkable gelatin-methacryloyl (GelMA) via mixing. This material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1 (HMGB1) from the nucleus to the cytoplasm. We further assessed the expression of inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and degeneration-related factors, such as type II collagen (COL-2), Aggrecan, matrix metallopeptidases-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 in rat nucleus pulpous cells. The level of IDD was analyzed through H&E, safranin-O staining and immunohistochemistry in rabbit samples. In vitro , we found that ASP-Lip@GelMA treatment significantly decreased inflammatory cytokines, MMP-3 and -13, and ADAMTS-4 and -5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the nucleus. In vivo, ASP-Lip@GelMA can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue defects. This composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications.

The Proteolysis of ECM in Intervertebral Disc Degeneration

“…Here we review recent advances in modulating ECM homeostasis for the treatment of IDD (Table 1). TA-functionalized polymer capsules Downregulate MMP-3 and ADAMTS-5 [119] Aspirin controllable release hydrogel Downregulate MMP-3/13 and ADAMTS-4/5 [120] Injectable microspheres load with TNFRII or APETx2 Downregulate MMP-3 and ADAMTS-5 via modulate local inflammation microenvironment [121,122] Gene therapy AAV2-TIMP1 promote synthesis of type II collagen [123] TGF-β3, CTGF and TIMP1 co-transduction Promote synthesis of aggrecan and type II collagen [124] ADAMTS-5 siRNA Downregulate ADAMTS-5 [125] PRP: Platelet-Rich Plasma, DHP: 1,4-dihydropyridine, TIMP-1: tissue inhibitor of metalloproteinase 1, CCL-5: C-C motif chemokine ligand 5, ALN: alendronate, TNFRII: tumor necrosis factor receptor type II. TGF-β3: transforming growth factor, CTGF: connective tissue growth factor, ADAMTS: A disintegrin and metalloprotease with thrombospondin motifs, MMP: Matrix metalloproteinase.…”

Follistatin‐Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF‐α and Smad Signaling Pathway

“…Inflammation and oxidative stress are thought to play important roles in disc degeneration [4,5]. Most previous studies showed that IDD was a passive process: the local homeostasis of intervertebral disc (IVD) tissues was destroyed, the biomechanical relationship of normal lumbar vertebrae was changed, and the number of local inflammatory cells and the secretion and synthesis of related inflammatory factors were altered [4,[6][7][8][9][10][11]. The significantly high expression of inflammatory factors is an important characteristic of the inflammatory microenvironment of the degenerative nucleus pulposus.…”

Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell

“…But there are still many problems between the microenvironment and transplanted cells. Although some ROS serve as signaling molecules in cells, excessive oxidative and inflammation production is harmful and has been implicated in progression of IVDD [ 46 ]. ROS production and nonspecific inflammation generated during the IVDD pathological process have been demonstrated in leading to loss of transplanted stem cells.…”