| Low back pain (LBP) is a very frequently encountered disorder, the incidence of which is second only to upper respiratory infections. In addition, LBP is also the predominant cause of disability. Disc degenerative diseases (DDD) are generally thought to be the main cause of LBP. DDD are caused by abnormal mechanical loading, genetic predisposition, reduced cell activity, or any combination of the three, inducing changes in the matrix composition and resulting in the deterioration of its biomechanical properties.Current therapies for DDD range from conservative management to invasive procedures such as discectomy, spinal fusion, total disc replacement, or NP (nucleus pulposus) replacement. Conservative management strategies include bed rest (although this is no longer recommended), analgesia, muscle relaxants, corticosteroids or local anesthetics and manipulation therapies, while all of which are mainly palliative. Surgical treatments such as discectomy and spinal fusion produce symptomatic relief by removing the disc tissue or sacrificing the mobility of spinal segments rather than repairing the degenerated discs. Although artificial disc replacement surgery has been demonstrated a promising future, many complications and shortcomings associated with this technology still need to be overcome.None of the surgical treatments for DDD are currently applied to deal with the inherent loss of functional native disc tissue; therefore, biological implants consistent with structure and function of intervertebral disc (IVD) and/or NP may be ideal candidates for reconstituting the degenerated discs and therefore treating DDD. With the rapid development of tissue engineering in recent years, IVD tissue engineering has provided a possibility for recovering the function of the IVD with in vitro development of functional tissue unit for implantation into the body. The aim of IVD tissue engineering is to induce regeneration of the degenerated disk in situ via biological manipulation. Among the three anatomical elements of IVD (the annulus fibrosus (AF), the NP, and the endplate), the gelatinous NP comprises randomly organized collagen fibers, radially arranged elastin fibers and a highly hydrated aggrecan containing gel. The highly hydrated proteoglycans in the NP are essential to maintain the osmotic pressure and therefore have a major effect on the load bearing properties of the disc. In addition, as DDD is believed to originate from a gradual loss of proteoglycans and water content in NP, most tissue engineering studies are focused on treatment of degenerated NP.Among the three principal components of tissue engineering (cells, scaffolds, and signals), the scaffold acts as a delivery vehicle, providing cells with temporary protection from unfavorable local implantation milieu. In addition, it should also create an environment that favors cell adhesion, proliferation, related gene expression and synthesis of new functional tissues. At present, although an extensive body of literature exists on NP tissue engineering scaffolds, few studies have mentioned specific scaffold materials that imitate the natural environmental condition of native NP. As the main function of a biological scaffold is to emulate the biological environment of the local tissue, a scaffold for the tissue engineered NP must therefore simultaneously provide the three principal extracellular matrix components of native NP: Collagenâ…¡(Câ…¡), Hyaluronan (HyA) and Chondroitin-6-sulfate (6-CS). According to the principal described above, we have constructed a novel engineered scaffold composed of Câ…¡, HyA and 6-CS (Câ…¡/HyA-CS) and assessed the bioactivity of the Câ…¡/HyA-CS scaffold in culturing rabbit NP cells in vitro by evaluating NP cell viability/proliferation, tissue-specific gene expression and extracellular matrix (ECM) formation. Furthermore, pre-cultured rabbit NP cell-seeded Câ…¡/HyA-CS tri-copolymer constructs were allografted into the lacunas of the recipient intervertebral discs immediately after disc nucleotomy. Regeneration of the intervertebral disc in vivo was assessed based on the magnetic resonance imaging (MRI) and Radiographic results of the operated discs and the viability and histologic status of the allografted cell-scaffold constructs.Our results are as following: when cultured in vitro for 28 days, the cell-scaffold hybrids maintained active cell viability/proliferation and exhibited a significantly increased sulfated glycosaminoglycan (s-GAG) content. In addition, rabbit NP cells cultured in the scaffold demonstrated a significantly higher level of Câ…¡and aggrecan gene expression and a significantly lower level of Collagenâ… (Câ… ) gene expression when compared with that of monolayer cells. Histological studies and scanning electron microscopy (SEM) further indicated newly secreted ECM deposits in the scaffolds. In vivo results documented survival of the allografted cells and ECM deposition, which finally resulted in maintenance of disc height and restoration of T2-weighted signal intensity on MRI. In conclusion, the NP-cell seeded Câ…¡/HyA-CS tri-copolymer implants may be an alternative substitute for degenerated NP after nucleotomy due to its satisfactory in vitro bioactivity and in vivo regenerative effect.
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