Interconnected porous hydroxyapatite ceramics for bone tissue engineering

Several porous calcium hydroxyapatite (HA) ceramics have been used clinically as bone substitutes, but most of them possessed few interpore connections, resulting in pathological fracture probably due to poor bone formation within the substitute. We recently developed a fully interconnected porous HA ceramic (IP-CHA) by adopting the ‘foam-gel’ technique. The IP-CHA had a three-dimensional structure with spherical pores of uniform size (average 150 μm, porosity 75%), which were interconnected by window-like holes (average diameter 40 μm), and also demonstrated adequate compression strength (10–12 MPa). In animal experiments, the IP-CHA showed superior osteoconduction, with the majority of pores filled with newly formed bone. The interconnected porous structure facilitates bone tissue engineering by allowing the introduction of mesenchymal cells, osteotropic agents such as bone morphogenetic protein or vasculature into the pores. Clinically, we have applied the IP-CHA to treat various bony defects in orthopaedic surgery, and radiographic examinations demonstrated that grafted IP-CHA gained radiopacity more quickly than the synthetic HA in clinical use previously. We review the accumulated data on bone tissue engineering using the novel scaffold and on clinical application in the orthopaedic field.

[1]  E. D. Rekow,et al.  MicroCT analysis of hydroxyapatite bone repair scaffolds created via three-dimensional printing for evaluating the effects of scaffold architecture on bone ingrowth. , 2008, Journal of biomedical materials research. Part A.

[2]  E. D. Rekow,et al.  In vivo bone response to 3D periodic hydroxyapatite scaffolds assembled by direct ink writing. , 2007, Journal of biomedical materials research. Part A.

[3]  N. Adachi,et al.  Transplantation of tissue-engineered osteochondral plug using cultured chondrocytes and interconnected porous calcium hydroxyapatite ceramic cylindrical plugs to treat osteochondral defects in a rabbit model. , 2007, Artificial organs.

[4]  Mitsuo Ochi,et al.  Augmentation of tendon attachment to porous ceramics by bone marrow stromal cells in a rabbit model , 2007, International Orthopaedics.

[5]  N. Adachi,et al.  Effects of interconnecting porous structure of hydroxyapatite ceramics on interface between grafted tendon and ceramics. , 2006, Journal of biomedical materials research. Part A.

[6]  H. Yoshikawa,et al.  Dual hydroxyapatite composite with porous and solid parts: experimental study using canine lumbar interbody fusion model. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[7]  H. Ohgushi,et al.  The Effect of Simulated Microgravity by Three-Dimensional Clinostat on Bone Tissue Engineering , 2005, Cell transplantation.

[8]  A. Nakamae,et al.  Prefabrication of vascularized bone graft using a combination of fibroblast growth factor-2 and vascular bundle implantation into a novel interconnected porous calcium hydroxyapatite ceramic. , 2005, Journal of biomedical materials research. Part A.

[9]  Hideki Yoshikawa,et al.  A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2). , 2005, Osteoarthritis and cartilage.

[10]  Hideki Yoshikawa,et al.  Capillary vessel network integration by inserting a vascular pedicle enhances bone formation in tissue-engineered bone using interconnected porous hydroxyapatite ceramics. , 2004, Tissue engineering.

[11]  H. Yoshikawa,et al.  Calcium hydroxyapatite ceramic implants in bone tumour surgery. A long-term follow-up study. , 2004, The Journal of bone and joint surgery. British volume.

[12]  H. Ohgushi,et al.  Bone Tissue Engineering Using Novel Interconnected Porous Hydroxyapatite Ceramics Combined with Marrow Mesenchymal Cells: Quantitative and Three-Dimensional Image Analysis , 2004, Cell transplantation.

[13]  H. Yoshikawa,et al.  Three-Dimensionally Engineered Hydroxyapatite Ceramics with Interconnected Pores as a Bone Substitute and Tissue Engineering Scaffold , 2003 .

[14]  H. Ohgushi,et al.  Calcium Phosphate Ceramics in Japan , 2003 .

[15]  M. Neo,et al.  Repair of segmental long bone defect in rabbit femur using bioactive titanium cylindrical mesh cage. , 2003, Biomaterials.

[16]  E. D. Rekow,et al.  Engineered cellular response to scaffold architecture in a rabbit trephine defect. , 2003, Journal of biomedical materials research. Part A.

[17]  E. D. Rekow,et al.  Performance of degradable composite bone repair products made via three-dimensional fabrication techniques. , 2003, Journal of biomedical materials research. Part A.

[18]  Hyun Min Kim,et al.  Repair of Segmental Long Bone Defect in Rabbit Femur using Bioactive Titanium Cylindrical Mesh Cage , 2002 .

[19]  K. Takaoka,et al.  Biodegradable Poly-d,l-Lactic Acid-Polyethylene Glycol Block Copolymers as a BMP Delivery System for Inducing Bone , 2001, The Journal of bone and joint surgery. American volume.

[20]  S. Simske,et al.  Long-term bone ingrowth and residual microhardness of porous block hydroxyapatite implants in humans. , 1998, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[21]  Marc A. Asher,et al.  Iliac Crest Bone Graft Harvest Donor Site Morbidity: A Statistical Evaluation , 1995, Spine.

[22]  Banwart Jc,et al.  Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. , 1995 .

[23]  K. Takaoka,et al.  Polylactic acid-polyethylene glycol block copolymer. A new biodegradable synthetic carrier for bone morphogenetic protein. , 1993, Clinical orthopaedics and related research.

[24]  N. Sharkey,et al.  Bone ingrowth and mechanical properties of coralline hydroxyapatite 1 yr after implantation. , 1993, Biomaterials.

[25]  H. Yoshikawa,et al.  The use of calcium hydroxyapatite ceramic in bone tumour surgery. , 1990, The Journal of bone and joint surgery. British volume.

[26]  R. Holmes,et al.  Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures. , 1989, Clinical orthopaedics and related research.

[27]  R. Holmes,et al.  Hydroxylapatite as a bone graft substitute in orthognathic surgery: histologic and histometric findings. , 1988, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[28]  R. Holmes,et al.  Hydroxyapatite and tricalcium phosphate bone graft substitutes. , 1987, The Orthopedic clinics of North America.

[29]  D. Sartoris,et al.  Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation. , 1986, Radiology.

[30]  J. Rodrigo,et al.  Contemporary Bone Graft Physiology and Surgery , 1985, Clinical orthopaedics and related research.

[31]  A. Uchida,et al.  The use of ceramics for bone replacement. A comparative study of three different porous ceramics. , 1984, The Journal of bone and joint surgery. British volume.

[32]  T. Akiyama,et al.  :A long term follow-up study , 1982 .

[33]  J. Steinkamp,et al.  Flow microfluorometric and light-scatter measurement of nuclear and cytoplasmic size in mammalian cells. , 1976, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[34]  H. Yoshikawa,et al.  Potential roles of bone morphogenetic proteins (BMPs) in skeletal repair and regeneration , 2006, Journal of Bone and Mineral Metabolism.

[35]  Hideki Yoshikawa,et al.  Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite. , 2005, Biomaterials.

[36]  PhD Hideki Yoshikawa MD,et al.  Bone tissue engineering with porous hydroxyapatite ceramics , 2005, Journal of Artificial Organs.

[37]  H. Yoshikawa,et al.  Novel hydroxyapatite ceramics with an interconnective porous structure exhibit superior osteoconduction in vivo. , 2002, Journal of biomedical materials research.

[38]  A I Caplan,et al.  Stem cell technology and bioceramics: from cell to gene engineering. , 1999, Journal of biomedical materials research.

[39]  V. Rosen,et al.  Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. , 1998, Clinical orthopaedics and related research.

[40]  H. Chambers,et al.  Complications of iliac crest bone graft harvesting. , 1996, Clinical orthopaedics and related research.

[41]  R. Holmes,et al.  Porous hydroxyapatite as a bone graft substitute in diaphyseal defects: A histometric study , 1987, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.