Current Status of Disc Repair and Regeneration

Abstract

Introduction Repair and regeneration efforts for intervertebral discs can be directed toward the annulus fibrosus (AF) and/or the nucleus pulposus (NP). Several different mechanical and biological approaches have recently been investigated for both disc components. We present a comprehensive literature research with a focus on biomaterials tested in vivo or in clinical trials for the treatment of disc degeneration. Methods Papers available in electronic databases such as PubMed, Web of Science, and Google Scholar by May 2013 were reviewed. The primary inclusion criterion was the presence of in vivo experiments or clinical trials. The secondary inclusion criterion was the ability to be categorized into one of the following four categories: (1) therapies with growth factors/cells, (2) gene/protein therapies, (3) annulus fibrosus repair, and (4) injectable biomaterials. Results Efforts to regenerate the NP focused on replenishing lost nuclear tissue by implantation of scaffolds with and without cell load or enhancing intrinsic synthesis of nuclear matrix by injection of human growth factors. Electrospun fibers were utilized as rigid scaffolds, collagen, and fibrin hydrogels as injectable scaffolds. Mesenchymal stem cells (MSC) or juvenile chondrocytes as allografts or xenografts have been predominately used as cell load. Cell/hydrogel combinations were successfully tested in various animal degeneration models. Cells proved to maintain viable in vivo and formed an extracellular matrix with a similar composition as the native NP. Typical degenerative parameters such as reduced disc height or loss of hyperintensity on MRIs were partially reversed. The growth factors osteogenic protein-1 and growth/differentiation factor-5 have been tested in rabbit disc degeneration models in vivo and proved to increase proteoglycan synthesis and extracellular matrix production of the NP. They showed to increase disc height and reverse histological and radiological degenerative changes in the rabbit spine. Injection of BMP-13 into sheep intervertebral discs found that it can prevent neovascularization and slow degenerative changes. MSC and juvenile chondrocyte injections for the treatment of degenerative disc disease demonstrated a significant reduction of pain scores in clinical trials with a maximum follow-up of 2 years. For annular repair, simple mechanical solutions such as special suture techniques or annuloplasty devices were initially tested but did not significantly alter annular healing strength or demonstrate long-term benefits in a clinical trial. Rigid biological implants using tissue-engineered AF constructs in vitro stimulate annular fibroblasts to produce extracellular matrix. Implants made from small intestinal submucosa reduced degenerative changes after annular incision in sheep spine in vivo. Recently, to improve clinical applicability, the potential of injectable biomaterials was investigated. Injectable genipin cross-linked fibrin hydrogels were shown to integrate with sections of human AF tissue and showed promising biomechanical and cell-seeding properties in vitro. Injectable riboflavin cross-linked collagen gel-proved viable to repair annular defects in the rat tail spine by enhancing intrinsic healing capabilities. This helped to retain nuclear tissue after inducing annular defects and inhibited degenerative changes defects in the rat spine. Conclusion Implantable biomaterials have the potential to integrate with host tissue and induce a regeneration process in the NP and AF. Several biomaterials have been tested in animal experiments for disc regeneration efforts and demonstrated the ability to partially reverse degenerative changes. Most of these data still have to be corroborated in clinical trials. Cell/scaffold combinations have already been tested in clinical trials to treat degenerative disc disease. However, results from long-term randomized trials with a greater patient population are not yet available. Disclosure of Interest Consultant for Lanx Consultant for BrainLab Consultant for DePuy-Synthes