elastin and Intervertebral-Disc-Displacement

The objectives of augmentation of the nucleus pulposus following disc removal are to prevent disc height loss and the associated biomechanical and biochemical changes. Flowable materials may be injected via a small incision, allowing minimally invasive access to the disc space. Fluids can interdigitate with the irregular surgical defects and may even physically bond to the adjacent tissue. Injectable biomaterials allow for incorporation and uniform dispersion of cells and/or therapeutic agents. Injectable biomaterials have been developed that may act as a substitute for the disc nucleus pulposus. Our work has focused on the evaluation of a recombinant protein copolymer consisting of amino acid sequence blocks derived from silk and elastin structural proteins as an injectable biomaterial for augmentation of the nucleus pulposus. This implant, NuCoretrade mark Injectable Nucleus is being developed by Spine Wave (Shelton, CT). The NuCoretrade mark material is comprised of a solution of the protein polymer and a polyfunctional cross-linking agent. The material closely mimics the protein content, water content, pH and complex modulus of the natural nucleus pulposus. Extensive mechanical testing, biocompatibility and toxicology testing have been performed on the material. Characterization studies indicate that the NuCoretrade mark Injectable Nucleus is able to restore the biomechanics of the disc following a microdiscectomy. Extensive biomaterial characterization shows the material to be non-toxic and biocompatible. The mechanical properties of the material mimic those of the natural nucleus pulposus. Thus NuCoretrade mark Injectable Nucleus is suitable to replace the natural nucleus pulposus following a discectomy procedure. Human clinical evaluation is underway in a multi center clinical study on the use of the material as an adjunct to microdiscectomy. Further clinical studies of the use of NuCoretrade mark Injectable Nucleus for treatment of early stage degenerative disc disease are planned in the near future. On-going efforts are characterizing the use of the material as a cell delivery vehicle for disc repair and reconstruction. Related development efforts are exploring methods for repair and regeneration of the cartilage endplate that are implemented to enhance the host-implant interface. Prior to the introduction of the above-mentioned biomaterial, our work proposes to utilize a process for the treatment of the vertebral endplates. The goal of this proc

Topics: Biocompatible Materials; Biopolymers; Elastin; Humans; Intervertebral Disc; Intervertebral Disc Displacement; Recombinant Fusion Proteins; Regeneration; Spine

This is an immunohistologic study of gene expression between patients and controls.This study aims to evaluate expression of the catalase gene in hypertrophied ligamentum flavum (LF) specimens obtained from patients with lumbar spinal canal stenosis (LSCS).LSCS is one of the most common spinal disorders. It is well known that LF hypertrophy plays an important role in the onset of LSCS. Although degenerative changes, aging, and mechanical stress are all thought to contribute to hypertrophy and fibrosis of the LF, the precise pathogenesis of LF hypertrophy remains unknown. Previous genetic studies have tried to determine the mechanism of LF hypertrophy. However, the association between catalase gene expression and LF hypertrophy has not yet been explored.. LF specimens were surgically obtained from 30 patients with spinal stenosis (LSCS group) and from 30 controls with lumbar disc herniation (LDH group). LF thickness was measured at the thickest point using calipers to an accuracy of 0.01 mm during surgical intervention. The extent of LF elastin degradation and fibrosis were graded (grades 0-4) by hematoxylin and eosin staining and Masson trichrome staining, respectively. The resulting LF measurements, histologic data, and immunohistologic results were then compared between the 2 groups.. The average LF thickness was significantly higher in the LSCS group than in the LDH group (5.99 and 2.95 mm, respectively, P = .004). Elastin degradation and fibrosis of the LF were significantly more severe in spinal stenosis samples than in the disc herniation samples (3.04 ± 0.50 vs 0.79 ± 0.60, P = .007; 3.01 ± 0.47 vs 0.66 ± 0.42, P = .009, respectively). Significantly lower expression of catalase was observed in the perivascular area of LF samples obtained from patients with LSCS compared with controls (61.80 ± 31.10 vs 152.80 ± 41.13, respectively, P = .009).. Our findings suggest that decreased expression of catalase is associated with LF hypertrophy in patients with LSCS.

Topics: Adult; Aged; Catalase; Elastin; Female; Fibrosis; Gene Expression; Humans; Hypertrophy; Intervertebral Disc Displacement; Ligamentum Flavum; Lumbar Vertebrae; Male; Middle Aged; Organ Size; Retrospective Studies; Spinal Stenosis

Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Curcumin; Delayed-Action Preparations; Drug Delivery Systems; Elastin; Female; Genetic Engineering; Hot Temperature; Humans; Inflammation; Intervertebral Disc Displacement; Mice; Mice, Inbred C57BL; Peptides; Sciatic Nerve; U937 Cells

Significant quantitative differences between macromolecular components of the nuclei pulposi of prolapsed human intervertebral discs and those taken at necropsy were found. The nuclei pulposi of prolapsed discs contained about twice more collagen in comparison to control tissues. The amount of type I and type III collagens grew in a higher degree in comparison to type II of this protein. A distinctly higher solubility of the prolapsed discs collagen, together with an increased aldehyde content in solubilized collagen fractions were observed. A distinct decrease in the amount of glycosaminoglycans, especially CH-4-S and CH-6-S were found. Furthermore, a significant increase in elastin content and its susceptibility to the proteolytic action of elastase were found. The significance of these phenomena for pathobiochemistry of disc prolapse is discussed.

Topics: Adult; Age Factors; Aged; Collagen; Elastin; Female; Glycosaminoglycans; Humans; Intervertebral Disc Displacement; Male; Middle Aged; Pancreatic Elastase