Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration.

Injectable hydrogel allows irregular surgical defects to be completely filled, lessens the risk of implant migration, and minimizes surgical defects due to the solution-gel state transformation. Here, we first propose a method for preparing oxidized hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) injectable hydrogel by chemical cross-linking under physiological conditions. Fourier transform infrared spectrometry and trinitrobenzene sulfonate assay were used to confirm the oxidation of hyaluronic acid. Rheological properties were measured to evaluate the working ability of the hydrogel for further clinical application. The oxi-HA/ADH in situ forming hydrogel can transform from liquid form into a gel-like matrix within 3-8 min, depending on the operational temperature. Furthermore, hydrogel degradation and cell assessment is also a concern for clinical application. Injectable oxi-HA/ADH8 hydrogel can maintain its gel-like state for at least 5 weeks with a degradation percentage of 40%. Importantly, oxi-HA/ADH8 hydrogel can assist in nucleus pulposus cell synthesis of type II collagen and aggrecan mRNA gene expression according to the results of real-time PCR analysis, and shows good biocompatibility based on cell viability and cytotoxicity assays. Based on the results of the current study, oxi-HA/ADH hydrogel may possess several advantages for future application in nucleus pulposus regeneration.

[1]  James D. Kang,et al.  Biologic modification of animal models of intervertebral disc degeneration. , 2006, The Journal of bone and joint surgery. American volume.

[2]  R. Bank,et al.  Molecular Changes in the Degenerated Goat Intervertebral Disc , 2008, Spine.

[3]  A Ratcliffe,et al.  Determination of collagen-proteoglycan interactions in vitro. , 1996, Journal of biomechanics.

[4]  E. Thonar,et al.  Recombinant osteogenic protein‐1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[5]  J. Urban,et al.  Cells From Different Regions of the Intervertebral Disc: Effect of Culture System on Matrix Expression and Cell Phenotype , 2002, Spine.

[6]  F. Lin,et al.  Preparation and characterization of pH sensitive poly(N-vinyl-2- pyrrolidone/itaconic acid) copolymer hydrogels , 2005 .

[7]  Rolando Barbucci,et al.  Amidic alginate hydrogel for nucleus pulposus replacement. , 2008, Journal of biomedical materials research. Part A.

[8]  M. Aebi,et al.  The Potential and Limitations of a Cell-Seeded Collagen/Hyaluronan Scaffold to Engineer an Intervertebral Disc-Like Matrix , 2003, Spine.

[9]  Matthew J. Allen,et al.  Preclinical Evaluation of a Poly (Vinyl Alcohol) Hydrogel Implant as a Replacement for the Nucleus Pulposus , 2004, Spine.

[10]  P. Puska,et al.  Is back pain increasing? Results from national surveys in Finland during 1978/9-1992. , 1994, Scandinavian journal of rheumatology.

[11]  W. Knudson,et al.  Hyaluronan and CD44: modulators of chondrocyte metabolism. , 2004, Clinical orthopaedics and related research.

[12]  W. Hennink,et al.  Characterization of the network structure of dextran glycidyl methacrylate hydrogels by studying the rheological and swelling behavior , 1995 .

[13]  J. P. Thompson,et al.  Stimulation of Mature Canine Intervertebral Disc by Growth Factors , 1991, Spine.

[14]  A. Tsantrizos,et al.  Nucleus Replacement With the DASCOR Disc Arthroplasty Device: Interim Two-Year Efficacy and Safety Results From Two Prospective, Non-Randomized Multicenter European Studies , 2009, Spine.

[15]  Lori A. Setton,et al.  Photocrosslinkable Hyaluronan as a Scaffold for Articular Cartilage Repair , 2004, Annals of Biomedical Engineering.

[16]  D. Aeschlimann,et al.  New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. , 1999, Journal of biomedical materials research.

[17]  V. Mow,et al.  Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[18]  British Standard,et al.  Biological evaluation of medical devices , 2006 .

[19]  Ashutosh Chilkoti,et al.  Swelling and mechanical behaviors of chemically cross-linked hydrogels of elastin-like polypeptides. , 2003, Biomacromolecules.

[20]  Christine E Schmidt,et al.  Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds. , 2003, Biotechnology and bioengineering.

[21]  M. Spector,et al.  Proteoglycans synthesized by canine intervertebral disc cells grown in a type I collagen-glycosaminoglycan matrix. , 2002, Tissue engineering.

[22]  T. Steffen,et al.  Biological evaluation of chitosan salts cross-linked to genipin as a cell scaffold for disk tissue engineering. , 2005, Tissue engineering.

[23]  M Fini,et al.  Hyaluronic acid hydrogel in the treatment of osteoarthritis. , 2002, Biomaterials.

[24]  D. Riches,et al.  Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages. , 1993, The Journal of clinical investigation.

[25]  L. Setton,et al.  Intervertebral Disc Cells Exhibit Differences in Gene Expression in Alginate and Monolayer Culture , 2001, Spine.

[26]  T. Niemeyer,et al.  Human Anulus Fibrosis and Nucleus Pulposus Cells of the Intervertebral Disc: Effect of Degeneration and Culture System on Cell Phenotype , 2005, Spine.

[27]  C. Perka,et al.  Cultivation of porcine cells from the nucleus pulposus in a fibrin/hyaluronic acid matrix , 2000, Acta orthopaedica Scandinavica.

[28]  Robert Stern,et al.  Hyaluronan fragments: an information-rich system. , 2006, European journal of cell biology.

[29]  Adrijana Preradovic,et al.  Quantitation of collagen I, collagen II and aggrecan mRNA and expression of the corresponding proteins in human nucleus pulposus cells in monolayer cultures , 2005, Cell and Tissue Research.

[30]  Van C. Mow,et al.  Is the Nucleus Pulposus a Solid or a Fluid? Mechanical Behaviors of the Nucleus Pulposus of the Human Intervertebral Disc , 1996, Spine.

[31]  P. Rochon,et al.  The prevalence of low back pain in the elderly. A systematic review of the literature. , 1999, Spine.

[32]  F Guilak,et al.  Compressive and shear properties of alginate gel: effects of sodium ions and alginate concentration. , 1999, Journal of biomedical materials research.

[33]  Ashutosh Chilkoti,et al.  Characterization of a genetically engineered elastin-like polypeptide for cartilaginous tissue repair. , 2002, Biomacromolecules.

[34]  Alexander R. Vaccaro,et al.  Nucleus Pulposus Replacement: Basic Science and Indications for Clinical Use , 2005, Spine.

[35]  V. Mow,et al.  Determination of kinetic changes of aggrecan-hyaluronan interactions in solution from its rheological properties. , 1994, Journal of biomechanics.

[36]  L. Vervoort,et al.  Inulin hydrogels as carriers for colonic drug targeting. Rheological characterization of the hydrogel formation and the hydrogel network. , 1999, Journal of pharmaceutical sciences.

[37]  C. D. Ray.  The PDN® prosthetic disc-nucleus device , 2002, European Spine Journal.

[38]  D. Anderson,et al.  Molecular pathogenic factors in symptomatic disc degeneration. , 2005, The spine journal : official journal of the North American Spine Society.

[39]  T. Taylor,et al.  Morphological studies of the canine intervertebral disc. The assignment of the beagle to the achondroplastic classification. , 1975, Research in veterinary science.

[40]  B. Caterson,et al.  Matrix Metalloproteinases And Aggrecanase: Their Role in Disorders of the Human Intervertebral Disc , 2000, Spine.

[41]  M. Pearcy,et al.  Lumbar Intervertebral Disc Heights in Normal Subjects and Patients with Disc Herniation , 1985, Spine.

[42]  G. Andersson.  Epidemiological features of chronic low-back pain , 1999, The Lancet.

[43]  N. Boos,et al.  2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption , 2002, European Spine Journal.