Synchrotron X-ray bioimaging of bone regeneration by artificial bone substitute of MegaGen Synthetic Bone and hyaluronate hydrogels.

Synchrotron X-ray bioimaging was successfully carried out to observe bone regeneration by a novel artificial bone substitute of bioactive MegaGen Synthetic Bone (MGSB) and hyaluronate (HA) hydrogels. A biphasic calcium phosphate of MGSB was prepared by chemical precipitation method, with a porous spherical morphology. On the basis of the fact that HA plays important roles in bone regeneration and promotes the differentiation, vascularization, and migration of stem cells, HA-cystamine (CYS) hydrogels with cleavable disulfide linkages were prepared to supply HA continuously for effective bone regeneration by their controlled degradation in vivo. Among seven different samples using Bio-OSS®, MGSB, and/or several kinds of HA hydrogels, MGSB/HA-CYS hydrogels resulted in the most significant bone regeneration in the calvarial critical bone defect of New Zealand white rabbits. Histological and histomorphometric analyses revealed that the bone regeneration by MGSB/HA-CYS hydrogels was as high as 43%, occupying 71% of the bone defect area with MGSB in the form of a calvarial bone plate in 4 weeks. After that, MGSB was bioabsorbed and replaced gradually with regenerated bones as observed in 8 weeks. Synchrotron X-ray imaging clearly confirmed the effective bone regeneration by MGSB/HA-CYS hydrogels, showing three-dimensional micron-scale morphologies of regenerated bones interconnected with MGSB. In addition, sequential nondestructive synchrotron X-ray tomographic analysis results from anterior to posterior of the samples were well matched with the histomorphometric analysis results. The clinically feasible artificial bone substitutes of MGSB/HA-CYS hydrogels will be investigated further for various bone tissue engineering applications using the synchrotron X-ray bioimaging systems.

[1]  Faleh Tamimi,et al.  Bone regeneration in rabbit calvaria with novel monetite granules. , 2008, Journal of biomedical materials research. Part A.

[2]  Byung-Soo Kim,et al.  Control of the molecular degradation of hyaluronic acid hydrogels for tissue augmentation. , 2008, Journal of biomedical materials research. Part A.

[3]  Richard O C Oreffo,et al.  Bridging the regeneration gap: stem cells, biomaterials and clinical translation in bone tissue engineering. , 2008, Archives of biochemistry and biophysics.

[4]  K. Shakesheff,et al.  The effect of mesenchymal populations and vascular endothelial growth factor delivered from biodegradable polymer scaffolds on bone formation. , 2008, Biomaterials.

[5]  R. Jung,et al.  Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate. , 2008, Clinical oral implants research.

[6]  Kitae E. Park,et al.  Effect of hyaluronic acid molecular weight on the morphology of quantum dot-hyaluronic acid conjugates. , 2008, International journal of biological macromolecules.

[7]  T. Buckland,et al.  Comparative performance of three ceramic bone graft substitutes. , 2007, The spine journal : official journal of the North American Spine Society.

[8]  Chao Wan,et al.  The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. , 2007, The Journal of clinical investigation.

[9]  O. Herzberg,et al.  Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis. , 2007, Biochemistry.

[10]  Sang Hoon Lee,et al.  Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. , 2007, Biomaterials.

[11]  S. Hahn,et al.  Injectable hyaluronic acid microhydrogels for controlled release formulation of erythropoietin. , 2007, Journal of biomedical materials research. Part A.

[12]  S. Hahn,et al.  Synthesis and degradation test of hyaluronic acid hydrogels. , 2007, International journal of biological macromolecules.

[13]  Norimasa Tsuji,et al.  Osteogenic effect of hyaluronic acid sodium salt in the pores of a hydroxyapatite scaffold , 2007 .

[14]  Tien-Min G. Chu,et al.  Segmental bone regeneration using a load-bearing biodegradable carrier of bone morphogenetic protein-2. , 2007, Biomaterials.

[15]  Robert Langer,et al.  In vivo engineering of organs: the bone bioreactor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Theis,et al.  Effects of bone morphogenetic protein-2 and hyaluronic acid on the osseointegration of hydroxyapatite-coated implants: an experimental study in sheep. , 2005, Journal of biomedical materials research. Part A.

[17]  K. Ooya,et al.  Blood-filled spaces with and without deproteinized bone grafts in guided bone regeneration. A histomorphometric study of the rabbit skull using non-resorbable membrane. , 2005, Clinical oral implants research.

[18]  J. Je,et al.  International consortium on phase contrast imaging and radiology beamline at the Pohang Light Source , 2004 .

[19]  S. Chang,et al.  Cranial repair using BMP-2 gene engineered bone marrow stromal cells. , 2004, The Journal of surgical research.

[20]  G Margaritondo,et al.  Synchrotron microangiography with no contrast agent , 2004, Physics in medicine and biology.

[21]  R. Carano,et al.  Angiogenesis and bone repair. , 2003, Drug discovery today.

[22]  M. Slevin,et al.  Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses* , 2002, The Journal of Biological Chemistry.

[23]  H. Redmond,et al.  Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Déjou,et al.  The biodegradation mechanism of calcium phosphate biomaterials in bone. , 2002, Journal of biomedical materials research.

[25]  G. Daculsi,et al.  Macroporous biphasic calcium phosphate ceramics versus injectable bone substitute: a comparative study 3 and 8 weeks after implantation in rabbit bone , 2001, Journal of materials science. Materials in medicine.

[26]  A. Kuijpers-Jagtman,et al.  Incorporation of particulated bone implants in the facial skeleton. , 1999, Biomaterials.

[27]  G. Daculsi,et al.  Macroporous biphasic calcium phosphate ceramics: influence of macropore diameter and macroporosity percentage on bone ingrowth. , 1998, Biomaterials.

[28]  A. Boskey,et al.  Matrix proteins and mineralization: an overview. , 1996, Connective tissue research.

[29]  B. Smedsrød Cellular events in the uptake and degradation of hyaluronan , 1991 .

[30]  G. Daculsi,et al.  Macroporous calcium phosphate ceramic for long bone surgery in humans and dogs. Clinical and histological study. , 1990, Journal of biomedical materials research.

[31]  W. Kimpton,et al.  Uptake and degradation of hyaluronan in lymphatic tissue. , 1988, The Biochemical journal.

[32]  A. Engström‐Làurent,et al.  The catabolic fate of hyaluronic acid. , 1986, Connective tissue research.