Biomimetism, biomimetic matrices and the induction of bone formation
Ugo Ripamonti,
Corresponding Author
Ugo Ripamonti
Bone Research Unit, Medical Research Council/University of the Witwatersrand, Johannesburg, South Africa
Correspondence to: Ugo RIPAMONTI, M.D., Ph.D., Bone Research Unit, Medical Research Council/University of the Witwatersrand, Medical School, 7 York Road, Parktown, Johannesburg 2193, South Africa.Tel.: +27 11 717-2144;Fax: +27 11 717-2300E-mail: [email protected]Search for more papers by this authorUgo Ripamonti,
Corresponding Author
Ugo Ripamonti
Bone Research Unit, Medical Research Council/University of the Witwatersrand, Johannesburg, South Africa
Correspondence to: Ugo RIPAMONTI, M.D., Ph.D., Bone Research Unit, Medical Research Council/University of the Witwatersrand, Medical School, 7 York Road, Parktown, Johannesburg 2193, South Africa.Tel.: +27 11 717-2144;Fax: +27 11 717-2300E-mail: [email protected]Search for more papers by this authorAbstract
- •
Introduction: the induction of bone formation, the emergence of the skeleton, of the vertebrates and of Homo species
- •
Different strategies for the induction of bone formation
- •
Biological significance of redundancy and synergistic induction of bone formation
- •
Biomimetism and biomimetic matrices self-assembling the induction of bone formation
-
The concavity: the shape of life and the induction of bone formation
-
- •
Influence of geometry on the expression of the osteogenic phenotype
- •
Conclusion and therapeutic perspectives on porous biomimetic matrices with intrinsic osteoinductivity
Bone formation by induction initiates by invocation of osteogenic soluble molecular signals of the transforming growth factor-β (TGF-β) superfamily; when combined with insoluble signals or substrata, the osteogenic soluble signals trigger the ripple-like cascade of cell differentiation into osteoblastic cell lines secreting bone matrix at site of surgical implantation. A most exciting and novel strategy to initiate bone formation by induction is to carve smart self-inducing geometric concavities assembled within biomimetic constructs. The assembly of a series of repetitive concavities within the biomimetic constructs is endowed with the striking prerogative of differentiating osteoblast-like cells attached to the biomimetic matrices initiating the induction of bone formation as a secondary response. Importantly, the induction of bone formation is initiated without the exogenous application of the osteogenic soluble molecular signals of the TGF-β superfamily. This manuscript reviews the available data on this fascinating phenomenon, i.e. biomimetic matrices that arouse and set into motion the mammalian natural ability to heal thus constructing biomimetic matrices that in their own right set into motion inductive regenerative phenomena initiating the cascade of bone differentiation by induction biomimetizing the remodelling cycle of the primate cortico-cancellous bone.
References
- 1 Ripamonti U, van den Heever B, Crooks J, et al . Long-term evaluation of bone formation by osteogenic protein-1 in the baboon and relative efficacy of bone-derived bone morphogenetic proteins delivered by irradiated xenogeneic collagenous matrices. J Bone Miner Res. 2000; 15: 1798–809.
- 2
Ripamonti U,
Ramoshebi LN,
Patton J,
et al
.
Soluble signals and insoluble substrata: novel molecular cues instructing the induction of bone. In: EJ Massaro,
JM Rogers, editors. The skeleton.
Totowa
: Humana Press; 2004. pp.
217–27.
10.1007/978-1-59259-736-9_15 Google Scholar
- 3 Ripamonti U, Ferretti C, Heliotis M. Soluble and insoluble signals and the induction of bone formation: molecular therapeutics recapitulating development. J Anat. 2006; 209: 447–68.
- 4 Ripamonti U, Duneas N. Tissue morphogenesis and regeneration by bone morphogenetic proteins. Plast Reconstr Surg. 1998; 101: 227–39.
- 5 Ripamonti U. Soluble osteogenic molecular signals and the induction of bone formation. Biomaterials. 2006; 27: 807–22.
- 6 Ripamonti U. Recapitulating development: a template for periodontal tissue engineering. Tissue Eng. 2007; 13: 51–71.
- 7 Ripamonti U, Ramoshebi LN, Matsaba T, et al . Bone induction by BMPs/OPs and related family members in primates. The critical role of delivery systems. J Bone Joint Surg. 2001; 83: 116–27.
- 8 Ripamonti U. Molecular signals in geometrical cues sculpt bone morphology. S Afr J Sci. 2004; 100: 355–67.
- 9 Ripamonti U. Soluble, insoluble and geometric signals sculpt the architecture of mineralized bone. J Cell Mol Med. 2004; 8: 169–80.
- 10
Ripamonti U,
Ramoshebi LN,
Patton J,
et al
.
Sculpting the architecture of mineralized tissue: tissue engineering of bone from soluble signals to smart biomimetic matrices. In: RH Muller,
O Kayser, editors. Pharmaceutical biotechnology.
Hoboken
,
NJ
: Wiley-VCH; 2004. pp.
281–97.
10.1002/3527602410.ch16 Google Scholar
- 11 Khouri RK, Koudsi B, Reddi AH. Tissue transformation into bone in vivo. A potential practical application. J Am Med Assoc. 1991; 226: 1953–5
- 12 Reddi AH. Regulation of cartilage and bone differentiation by bone morphogenetic proteins. Curr Opin Cell Biol. 1992; 4: 850–5.
- 13 Langer R, Vacanti JP. Tissue engineering. Science. 1993; 260: 920–6.
- 14 Reddi AH. Symbiosis of biotechnology and biomaterials: applications in tissue engineering of bone and cartilage. J Cell Biochem. 1994; 56: 192–5.
- 15 Hubbell JA. Biomaterials in tissue engineering. Biotechnology. 1995; 13: 565–76.
- 16 Ripamonti U, Duneas N. Tissue engineering of bone by osteoinductive biomaterials. MRS Bulletin. 1996; 21: 36–9.
- 17 Reddi AH. Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials. Tissue Eng. 2000; 6: 351–9.
- 18
Ripamonti U.
Osteogenic proteins of the TGF-β superfamily. In: HL Henry,
AW Norman, editors. Encyclopedia of hormones.
Amsterdam
: Austin Academic Press; 2003. pp.
80–6.
10.1016/B0-12-341103-3/00319-3 Google Scholar
- 19 Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nature Biotechnol. 1988; 16: 247–52.
- 20 Urist MR. Bone: formation by autoinduction. Science. 1965; 150: 893–9.
- 21 Sampath TK, Reddi AH. Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. Proc Natl Acad Sci USA. 1981; 78: 7599–603.
- 22 Sampath TK, Reddi AH. Homology of bone-inductive proteins from human, monkey, bovine and rat extracellular matrix. Proc Natl Acad Sci USA. 1983; 80: 6591–5.
- 23 Luyten FP, Cunningham NS, Ma S, et al . Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation. J Biol Chem. 1989; 264: 13377–80.
- 24 Ripamonti U, Ma S, Cunningham N, et al . Initiation of bone regeneration in adult baboons by osteogenin, a monemorphogenetic protein. Matrix. 1992; 12: 369–80.
- 25 Wozney JM, Rosen V, Celeste AJ, et al . Novel regulators of bone formation: molecular clones and activities. Science. 1988; 242: 1528–34.
- 26 Sampath TK, Maliakal JC, Hauschka PV, et al . Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem. 1992; 267: 20352–62.
- 27 Ripamonti U. Smart biomaterials with intrinsic osteoinductivity; geometric control of bone differentiation. In: JE Davis, editor. Bone engineering. Toronto : EM2 Corporation; 2000. 215 pp.
- 28 Sacerdotti C, Frattin G. Sulla produzione eteroplastica dell’osso. R Acad Med Torino. 1901; 27: 825–36.
- 29 Huggins CB. The formation of bone under the influence of epithelium of the urinary tract. Arch Surg. 1931; 22: 377–408.
- 30 Levander G. A Study of bone regeneration. Surg Gynec Obstetr. 1938; 67: 705–14.
- 31 Levander G. Tissue induction. Nature. 1945; 155: 148–9.
- 32 Bridges JB, Pritchard JJ. Bone and cartilage induction in the rabbit. J Anat. 1958; 92: 28–38.
- 33 Moss ML. Extraction of an osteogenic inductor factor from bone. Science. 1958; 127: 755–6.
- 34 Trueta J. The role of the vessels in osteogenesis. J Bone Joint Surg. 1963; 45: 402–18.
- 35 Urist MR, Silverman BF, Buring K, et al . The bone induction principle. Clin Orthop. 1967; 53: 243–83.
- 36 Reddi AH, Hugging CB. Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci USA. 1972; 69: 1601–5.
- 37 Levander G, Willestaedt H. Alcohol-soluble osteogenetic substance from bone marrow. Nature. 1946; 3992: 587.
- 38 Urist MR, McLean FC. Osteogenetic potency and new bone formation by induction in transplants to the anterior chamber of the eye. J Bone Joint Surg Am. 1952; 34: 443–76.
- 39 Friedlaender GE, Perry CR, Cole JD, et al . Osteogenic protin-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am. 2001; 83A; S151–8.
- 40 Govender S, Csimma C, Genant HK, et al . Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002; 84A: 2123–34.
- 41 Ripamonti U, Reddi AH. Bone morphogenetic proteins: applications in plastic and reconstructive surgery. Adv Plast Reconstr Surg. 1995; 11: 47–73.
- 42 Heng BC, Cao T, Stanton LW, et al . Strategies for directing the differentiation of stem cells into the osteogenic lineage in vitro. J Bone Miner Res. 2004; 19: 1379–94.
- 43 Young HE, Duplaa C, Katz R, et al . Adult-derived stem cells and their potential for use in tissue repair and molecular medicine. J Cell Mol Med. 2005; 9: 753–69.
- 44 Steven MM, Marini RP, Schaefer D, et al . In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci USA. 2005; 202: 11450–5.
- 45 Warnke PH, Springer ING, Wiltfang J, et al . Growth and transplantation of a custom vascularised bone graft in a man. Lancet. 2004; 364: 766–70.
- 46 Heliotis M, Lavery KM, Ripamonti U, et al . Transformation of a prefabricated hydroxyapatite/osteogenic protein-1 implant into a vascularised pedicled bone flap in the human chest. Int J Oral Maxillofac Surg. 2006; 35: 265–9.
- 47 Roberts AB, Sporn MB, Assoian RK, et al . Transforming growth factor type β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA. 1986; 83: 4167–71.
- 48 Ripamonti U, Duneas N, van den Heever B, et al . Recombinant transforming growth factor-β1 induces endochondral bone in the baboon and synergizes with recombinant osteogenic protein-1 (bone morphogenetic protein-7) to initiate rapid bone formation. J Bone Miner Res. 1997; 2: 1584–95.
- 49 Duneas N, Crooks J, Ripamonti U. Transforming growth factor-β1: induction of bone morphogenetic protein genes expression during endochondral bone formation in the baboon, and synergistic interaction with osteogenic protein-1 (BMP-7). Growth Factors. 1998; 15: 259–77.
- 50 Ripamonti U, Crooks J, Matsaba T, et al . Induction of endochondral bone formation by recombinant human transforming growth factor-β2 in the baboon (Papio ursinus). Growth Factors. 2000; 17: 269–85.
- 51 Ripamonti U, Ramoshebi LN, Teare J, et al . The induction of endochondral bone formation by transforming growth factor-β3: experimental studies in the non-human primate Papio ursinus. J Cell Mol Med. 2008; 12: 1029–48.
- 52 Ripamonti U, Ferretti C, Heliotis M. Soluble molecular signals and the induction of bone formation (Chapter 31). In: B Guyuron, JA Persing, E Eriksson, editors. Plastic surgery: indications and practice. Elsevier Global Medicine; 2008; in press.
- 53 Ripamonti U, Heliotis M, Ferretti C. Bone morphogenetic proteins and the induction of one formation: from laboratory to patients. Oral Maxillofac Surg Clin North Am. 2007; 19: 575–89.
- 54 Ripamonti U, van den Heever B, van Wyk J. Expression of the osteogenic phenotype in porous hydroxyapatite implanted extra skeletally in baboons. Matrix. 1993; 13: 491–502.
- 55 Ripamonti U, Crooks J, Kirkbride AN. Sintered porous hydroxyapatites with intrinsic osteoinductive activity: geometric induction of bone formation. S Afri J Sci. 1999; 95: 335–43.
- 56 Reddi AH. Bone morphogenesis and modeling: soluble signals sculpt osteosomes in the sold state. Cell. 1997; 89: 159–61.
- 57 Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Eng J Med. 1995; 332: 305–11.
- 58 Parfitt AM, Mundy GR, Roodman GD, et al . A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J Bone Miner Res. 1996; 11: 150–9.
- 59 Ripamonti U, Herbst N-N, Ramoshebi LN. Bone morphogenetic proteins in craniofacial and periodontal tissue engineering: experimental studies in the non-human primate (Papio ursinus). Cytokine Growth Factor Rev. 2005; 16: 357–68.
- 60 Sampath TK, Rashka KE, Doctor JS, et al . Drosophila TGF-β superfamily proteins induce endochondral bone formation in mammals. Proc Natl Acad Sci USA. 1993; 90: 6004–8.
- 61 Ripamonti U, Richter PW, Thomas ME. Self-inducing shape memory geometric cues embedded within smart hydroxyapatite-based biomimetic matrices. Plast Reconstr Surg. 2007; 120: 1797–807.
- 62 Habibovic P, Sees TM, van den Doel MA, et al . Osteoinduction by biomaterials – physicochemical and structural influences. J Biomed Mater Res. 2006; 77: 747–62.
- 63 Habibovic P, de Groot K. Osteoinductive biomaterials – properties and relevance in bone repair. J Tissue Eng Regen Med. 2007; 1: 25–32.
- 64 Yuan H, Li Y, de Bruijn JD, et al . Tissue responses of calcium phosphate cement: a study in dogs. Biomaterials. 2000; 21: 1283–90.
- 65 Yuan H, Yang Z, de Bruijn JD, et al . Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog. Biomaterials. 2001; 22: 2617–23.
- 66 Le Nihouannen D, Daculsi G, Saffarzadeh A, et al . Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles. Bone. 2005; 36: 1086–93.
- 67 Yuan H, van Blitterswijk CA, de Groot K, et al . Cross-species comparison of ectopic bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) scaffolds. Tissue Eng. 2006; 12: 1607–15.
- 68 Fellah BH, Gauthier O, Weiss P, et al . Osteogenicity of biphasic calcium phosphate ceramics and bone autograft in a goat model. Biomaterials. 2008; 29: 1177–88.
- 69 Li X, van Blitterswijk CA, Feng Q, et al . The effect of calcium phosphate microstructure on bone-related cells in vitro. Biomaterials. 2008: 29: 3306–16.
- 70 de Groot K. Carriers that concentrate native bone morphogenetic protein in vivo. Tissue Eng. 1998; 4: 337–41.
- 71 Ripamonti U. Embedding molecular signals in biomimetic matrices for regenerative medicine. S Afr J Sci. 2006; 102: 211–6.
- 72 Sanchez C, Arribart H, Guille MMG. Biomimetism and bioinspiration as tools for the design of innovative materials and systems. Nature Mat. 2005; 4: 277–88.
- 73 Fratzl P. Biomimetic materials research: what can we really learn from nature’s structural materials? J R Soc Interface. 2007; 4: 637–42.
- 74 Ingber DE, Mow VC, Butler D, et al . Tissue engineering and developmental biology: going biomimetic. Tissue Eng. 2006; 12: 3265–83.
- 75 Vlodavsky I, Folkman J, Sullivan R, et al . Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci USA. 1987; 84: 2292–6.
- 76 Folkman J, Klagsbrun M, Sasse J, et al . A heparin-bind angiogenic protein – basic fibroblast growth factor – is stored within basement membranes. Am J Pathol. 1988; 130: 393–400.
- 77 Ingber DE, Folkman J. How does extracellular matrix control capillary morphogenesis? Cell. 1989; 58: 803–5.
- 78 Paralkar VM, Nandekar AKN, Pointer RH, et al . Interaction of osteogenin, a heparin binding bone morphogenetic protein, with type IV collagen. J Biol Chem. 1990; 265: 17281–4.
- 79 Paralkar VM, Vukicevic S, Reddi AH. Transforming growth factor β type1 binds to collagen type IV of basement membrane matrix: implications for development. Dev Biol. 1991; 143: 303–8.
- 80 Anderson HC, Hodges PT, Aguilera M, et al . Bone morphogenetic protein (BMP) localization in developing human and rat growth plate, metaphysis, epiphysis, and articular cartilage. J Histochem Cytochem. 2000; 48: 1493–502.
- 81
Schilling AF,
Filke S,
Brink S,
et al
.
Osteoclasts and biomaterials.
Eur J Trauma.
2006; 32: 107–13.
10.1007/s00068-006-6043-1 Google Scholar
- 82 Champagne CM, Takebe J, Offenbacher S, et al . Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone. 2002; 30: 26–31.
- 83 Takebe J, Champagne CM, Offenbacher S, et al . Titanium surface topography alters cell shape and modulates bone morphogenetic protein 2 expression in the J774A.1 macrophage cell line. J Biomed Mater Res. 2003; 64: 207–16.
- 84 Honda Y, Anada T, Kamakura S, et al . Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line. Biochem Biophys Res Commun. 2006; 345: 1155–60.
- 85 Kondo N, Ogose A, Tokunaga K, et al . Osteoinduction with highly purified β-tricalcium phosphate in dog dorsal muscles and the proliferation of osteoclasts before heterotopic bone formation. Biomaterials. 2006; 27: 4419–27.
- 86 Hunt TK, Burke J, Barbul A, et al . Wound healing. Science. 1999; 284: 1775.
- 87 Reddi AH, Huggins CB. Influence of geometry of transplanted tooth and bone on transformation of fibroblasts. Proc Soc Exp Biol Med. 1973; 143: 634–7.
- 88 Sampath TK, Reddi AH. Importance of geometry of the extracellular matrix in endochondral bone differentiation. J Cell Biol. 1984; 98: 2192–7.
- 89 Reddi AH. Bone matrix in the solid state: geometric influence on differentiation of fibroblasts. Adv Biol Med Phys. 1974; 15: 1–18.
- 90 Ripamonti U, Ma S, Reddi AH. The critical role of geometry of porous hydroxyapatite delivery system in induction of bone by osteogenin, a bone morphogenetic protein. Matrix. 1992; 12: 202–12.
- 91
Kuboki Y,
Takita H,
Kobayashi D,
et al
.
BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and non feasible structures: topology of osteogenesis.
J Biomed Mat Res.
1998; 39: 190–9.
10.1002/(SICI)1097-4636(199802)39:2<190::AID-JBM4>3.0.CO;2-K CAS PubMed Web of Science® Google Scholar
- 92 Kuboki Y, Saito T, Murata M, et al . Two distinctive BMP-carriers induce zonal chondrogenesis and membranous ossification, respectively: geometrical factors of matrices for cell-differentiation. Connect Tissue Res. 1995; 32: 219–26.
- 93 Kuboki Y, Jin Q, Takita H. Geometry of carriers controlling phenotypic expression in BMP-induced osteogenesis and chondrogenesis. J Bone Joint Surg Am. 2001; 83A: 105–15.
- 94 van Eeden SP, Ripamonti U. Bone differentiation in porous hydroxyapatite in baboons is regulated by the geometry of the substratum: implications for reconstructive craniofacial surgery. Plast Reconstr Surg. 1994; 93: 959–66.
- 95 Keith A. Concerning the origin and nature of osteoblasts. Proc Royal Soc Med. 1927; 21: 301–7.
- 96 Ripamonti U. Inductive bone matrix and porous hydroxylapatite composites in rodents and nonhuman primates. Handbook of bioactive ceramics. Boca Raton , FL : CRC Press; 1990. Vol II: pp. 245–53.
- 97 Ripamonti U. The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral. J Bone Joint Surg Am. 1991; 73: 692–703.
- 98 Hall BK Myake T. All for one and one for all: condensations and the initiation of skeletal development. Bioessays. 2000; 22: 138–47.
- 99 Winter GD, Simpson BJ. Heterotopic bone formed in a synthetic sponge in the skin of young pigs. Nature. 1969; 223: 88–90.
- 100 Ripamonti U. Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials. 1996; 17: 31–5.
- 101 Ripamonti U. Calvarial reconstruction in baboons with porous hydroxypatite. J Craniofac Surg. 1992; 3: 149–59.
- 102 Yamasaki H, Sakai H. Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs. Biomaterials. 1992; 13; 308–12.
- 103 Gosain AK, Song L, Riordan P, et al . A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part I. Plast Reconstr Surg. 2002; 109: 619–30.
- 104 Gosain AK, Riordan P, Song L, et al . A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part II. Bioengineering implants to optimize bone replacement in reconstruction of cranial defects. Plast Reconstr Surg. 2004; 114: 1155–63.
- 105 Ingber DE, Folkman J. How does extracellular matrix control capillary morphogenesis? Cell. 1989; 58: 803–5.
- 106 Folkman J, Greenspan HP. Influence of geometry on control of cell growthx. Biochim Biophys Acta. 1975; 417: 211–36.
- 107 Bissell MJ, Barcellos-Hoff MH. The influence of extracellular matrix on gene expression: is structure the message? J Cell Sci Suppl. 1987; 8: 327–43.
- 108 Li L, Xie T. Stem cell niche: structure and function. Ann Rev Cell Dev Biol. 2005; 21: 605–31.
- 109 Lensch MW, Daheron L, Schlager TM. Pluripotent stem cells and their niches. Stem Cell Rev. 2006; 2: 185–202.
- 110 Zheng B, Cao B, Crisan M, et al . Prospective identification of myogenic endothelial cells in human skeletal muscle. Nat Biotechnol. 2007; 25: 1025–34.
- 111 Ripamonti U. Bone induction by recombinant human osteogenic protein -1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF -β superfamily. J Cell Mol Med. 2005; 9: 911–28.
- 112 Termaat MF, Den Boer FC, Bakker FC, et al . Bone morphogenetic proteins. Development and clinical efficacy in the treatment of fractures and bone defects. J Bone Joint Surg Am. 2005; 87: 1367–78.
- 113 Daculsi G, Laboux O, Malard O, et al . Current state of the art of biphasic calcium phosphate bioceramics. J Mater Sci Mater Med. 2003; 14: 195–200.
- 114 Daculsi G, Layrolle P. Osteoinductive properties of micro macroporous biphasic calcium phosphate bioceramics. Key Eng Mater. 2004; 254–56: 1005–8.
- 115 Yang Z, Yuan H, Tong W, et al . Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics: variability among different kinds of animals. Biomaterials. 1996; 17: 2131–7.
- 116 Li S, de Wijn JR, Li J, et al . Macroporous biphasic calcium phosphate scaffold with high permeability/porosity ratio. Tissue Eng. 2003; 9: 535–48.
- 117 Ripamonti U, Richter PW, Nilen RWN, et al . Biomimetic smart hydroxyapatite/biphasic tricalcium phosphate biomatrices induce bone formation. Key Eng Mater. 2008; 361–363: 981–84.
- 118 Ripamonti U, Richter PW, Nilen RWN, et al . The induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus. J Cell Mol Med. 2008; 12: 1029–48.
Citing Literature
