| Low back pain (LBP) is an extremely common disorder in modern society, the incidence of which is second only to upper respiratory infections in US. Disc degenerative disease (DDD) is generally thought to be the main cause for discogenic LBP. As the aging process of the population in our country, DDD will impact the people in living and working more and more severely.Treatment of DDD remains still a great challenge to both clinical physicians and basic researchers. Conservative treatment modalities involve physical therapy and medications. For those patients who fail extensive conservative treatment, surgical treatment may be considered and usually involves discectomy or fusion of the involved IVD levels. Although discectomy and spine fusion have relieved the suffering of many patients, these lead to an irreversible loss of function of the treated segment with the resulting risks of adjacent segment degeneration and segmental instability.Several alternatives to discectomy and spinal fusion include IVD allografts transplantation and fabrication of prosthetic implants. Although the use of IVD allografts has shown promise in several studies, the challenges of such approaches include long-term viability and mechanical stability, as well as supply of donor tissue for clinical applications. Recently, non-fusion techniques including total disc arthroplasty and NP prostheses have shown promising clinical results, however the long-term performance of these implants has yet to be tested. On the other hand, all of those disc prostheses under investigations are composed of variable synthetic materials, which could hardly mimic the biological and biomechanical properties of the native IVD.In recent years, with the rapid development of tissue engineering technique, surgery has entered a new era of regenerative medicine. Tissue engineered IVD may be an ideal therapeutic regimen for reconstituting the structure and functions of degenerated discs and therefore treating DDD.In our previous studies, we fabricated a novel NP scaffold using CⅡ, HyA and 6-CS, the main components of the ECM of native NP, with techniques of freeze-drying and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) cross-linking. And we also constructed a novel AF scaffold using DBMG. In vitro studies have demonstrated that both CⅡ/HyA-CS and DBMG scaffolds have good biochemical properties and biocompatibility as well as satisfactory biosynthetic activity. Although both approaches show promise, construction of the composite IVD to regenerate AF and NP tissue as a unit has not been studied. The aim of the current study was to construct the AF-NP composition using the aforesaid scaffolds and to assess the gross and histological morphology and biochemical properties of the engineered constructs after implanting into the subcutaneous space of the dorsum of athymic mice for certain time period.Our results are as following: The cell-scaffold hybrids were implanted in the subcutaneous space of the dorsum of athymic mice and harvested at 4, 8, and 12 weeks. At each time point, the gross and histological morphology and biochemical properties were evaluated. Our results are as following: the gross morphology and histology of the composite resembled those of native IVD. Morphological studies revealed progressive tissue formation and junction integration between AF and NP regions. Biochemical composition detection indicated that the content of DNA, proteoglycan and hydroxyproline increased with time, and were similar to native tissue at 12 weeks. Collagen gene expression analysis showed the expression of CⅠand CⅡin AF and NP regions appears to be similar to that in native IVD. All these results demonstrated the feasibility of creating a tissue-engineered composite IVD with similar morphological and biochemical properties to the native tissue. |
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