Fucoidan-loaded nanofibrous scaffolds promote annulus fibrosus repair by ameliorating the inflammatory and oxidative microenvironments in degenerative intervertebral discs

Tissue engineering holds potential in the treatment of intervertebral disc degeneration (IDD). However, implantation of tissue engineered constructs may cause foreign body reaction and aggravate the inflam-matory and oxidative microenvironment of the degenerative intervertebral disc (IVD). In order to ame-liorate the adverse microenvironment of IDD, in this study, we prepared a biocompatible poly (ether carbonate urethane) urea (PECUU) nanofibrous scaffold loaded with fucoidan, a natural marine bioac-tive polysaccharide which has great anti-inflammatory and antioxidative functions. Compared with pure PECUU scaffold, the fucoidan-loaded PECUU nanofibrous scaffold (F-PECUU) decreased the gene and pro-tein expression related to inflammation and the oxidative stress in the lipopolysaccharide (LPS) induced annulus fibrosus cells (AFCs) significantly ( p < 0.05). Especially, gene expression of Il 6 and Ptgs2 was de-creased more than 50% in F-PECUU with 3.0 wt% fucoidan (HF-PECUU). Moreover, the gene and pro-tein expression related to the degradation of extracellular matrix (ECM) were reduced in a fucoidan concentration-dependent manner significantly, with increased almost 3 times gene expression of Col1a1 and Acan in HF-PECUU. Further, in a 'box' defect model, HF-PECUU decreased the expression of COX-2 and deposited more ECM between scaffold layers when compared with pure PECUU. The disc height and nucleus pulposus hydration of repaired IVD reached up to 75% and 85% of those in the sham group. In addition, F-PECUU helped to maintain an integrate tissue structure with a similar compression modulus to that in sham group. Taken together, the F-PECUU nanofibrous scaffolds showed promising potential to promote AF repair in IDD treatment by ameliorating the harsh degenerative microenvironment.

Automated summary

In this study, researchers developed a nanofibrous scaffold loaded with fucoidan, a natural marine polysaccharide with anti-inflammatory and antioxidative functions, to alleviate the adverse microenvironment of intervertebral disc degeneration (IDD). The results showed that the fucoidan-loaded scaffold significantly decreased the expression of genes and proteins related to inflammation and oxidative stress. Moreover, it reduced the degradation of extracellular matrix and promoted disc repair, indicating promising potential for IDD treatment.