Tissue engineering is the emerging field of science developing techniques for fabrication of new tissues for replacement based on principles of cell and developmental biology and biomaterials. Morphogenesis is the cascade of pattern formation and the attainment of form of the various organs and the organism as a whole. The periodontium consists of the periodontal ligament, cementum, and alveolar bone. Bone has considerable potential for regeneration and therefore is a prototypic model for tissue engineering. The three main ingredients for tissue engineering are regulatory signals, responding stem cells, and extracellular matrix. Recent advances in molecular biology of the bone morphogenetic proteins (BMPs) have set the stage for tissue engineering of bone and related tissues, including the periodontium. Bone-derived BMPs, with a collagenous matrix as carrier, induced cementum and alveolar bone regeneration in surgically created furcation defects in the primate. It is noteworthy that there was morphogenesis of periodontal ligament and a faithful insertion of Sharpey's fibers into cementum. In the same furcation model, recombinant human osteogenic protein-1 (rhOP-1, also known as BMP-7), in conjunction with the collagenous carrier, induced extensive cementogenesis with insertion of Sharpey's fibers into the newly formed cementum. The observation that BMPs induce cementogenesis and periodontal ligament formation indicates that these proteins may have multiple functions in vivo not limited to cartilage and bone induction. The rapid advances in the molecular biology of BMPs and their receptors bode well for novel strategies to engineer the regeneration of the periodontal tissues.
References
1.
American Academy of Periodontology (1986). Glossary of periodontic terms. J Periodontol56(Suppl):1-31.
2.
Bennett JH, Hunt P., Thorogood P. (1995). Bone morphogenetic protein-2 and 4 expression during murine orofacial development. Arch Oral Biol40:847-854.
3.
Bowers G., Reddi AH (1991). Regenerating the periodontium in advanced periodontal disease. J Am Dent Assoc122:45-48.
4.
Bowers GM, Schallhorn RG, Mellonig JT (1982). Histologic evaluation of new attachment in human intrabony defects. A literature review. J Periodontal53:509-514.
5.
Bowers G., Felton F., Middleton C., Glynn D., Sharp S., Mellonig J., et al. (1991). Histologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone allograft and with purified bovine collagen. J Periodontal62:690-702.
6.
Caffesse RG, Holden MJ, Kon S., Nasjleti CE (1985). The effect of citric acid and fibronectin application on healing following surgical treatment of naturally occurring periodontal disease in beagle dogs. J Clin Periodontol12:578-590.
7.
Celeste AJ, lannazzi JM, Taylor JA, Hewick RC, Rosen V., Wang EA, et al. (1990). Identification of transforming growth factor β family members present in bone-inductive protein purified from bovine bone. Proc Natl Acad Sci USA87:9843-9847.
8.
Chang SC, Hoang B., Thomas JT, Vukicevic S., Luyten FP, Ryba NIP, et al. (1994). Cartilage-derived morphogenetic proteins: New members of the transforming growth factor-β superfamily predominantly expressed in long bones during human embryonic development. J Biol Chem269:28227-28324.
9.
Cho MI, Lin WL, Genco RJ (1995). Platelet-derived growth factor-modulated guided tissue regenerative therapy. J Periodontol66:522-530.
10.
Cook SD, Wolfe MW, Salkeld SL, Rueger DC (1995). Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates. J Bone Joint Surg77(A):734-750.
11.
Cunningham NS, Jenkins NA, Gilbert DJ, Copeland NG, Reddi AH, Lee S.-J. (1995). Growth/differentiation factor-10: A new member of the transforming growth factor-β superfamily related to bone morphogenetic protein-3. Growth Factors12:99-109.
12.
Ferguson EL, Anderson KV (1992). Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the drosophila embryo. Cell71:451-461.
13.
Giannobile WV, Finkelman RD, Lynch SE (1994). Comparison of canine and non-human primate animal models for periodontal regenerative therapy: Results following a single administration of PDGF/IGF-1. J Periodontol65:1158-1168.
14.
Gottlow J., Nyman S., Karring T., Lindhe J. (1984). New attachment formation as a result of controlled tissue regeneration. J Clin Periodontol11:494-503.
15.
Hammonds RG, Schwall R., Dudley A., Berkemeier L., Lai C., Lee J., et al. (1991). Bone inducing activity of mature BMP-2b produced from a hybrid BMP-2a/2b precursor. Mol Endocrinol5:149-155.
16.
Heikinheimo K. (1994). Stage-specific expression of decapentaplegic-Vg-related genes 2,4, and 6 (bone morphogenetic proteins 2, 4, and 6) during human tooth morphogenesis. J Dent Res73:590-597.
17.
Helder MN, Ozkaynak E., Sampath TK, Luyten FP, Latin V., Oppermann H., et al. (1995). Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in human and mouse development. J Histochem Cytochem43:1035-1044.
18.
Iglhaut J., Aukhil I., Simpson DM, Johnston MC, Kock G. ( 1988). Progenitor cell kinetics during guided tissue regeneration in experimental periodontal wounds. J Periodont Res23:107-117.
19.
Jones CM, Lyons KM, Hogan BLM (1991 ). Involvement of bone morphogenetic protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development111:531-542.
20.
Kessler E. Takahara K., Biniaminov L., Brusel M., Greenspan DS (1996). Bone morphogenetic protein-1: The type I procollagen C-proteinase. Science271:360-362.
21.
Lee S.-J. (1990). Identification of a novel member (GDF-1) of the transforming growth factor-beta super family. Mol Endocrinol4:1034-1040.
22.
Luyten FP, Cunningham NS, Ma S., Muthukumaran N., Hammonds RG, Nevins WB, et al (1989). Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation. J Biol Chem264:13377-13380.
23.
Lynch SE (1992). Methods for evaluation of regenerative procedures. J Periodontol63:1085-1092.
24.
Lynch SE, Williams RC, Poison AM, Howell TH, Reddy MS, Zappa UE, et al. (1989). A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration. J Clin Periodontol16:545-548.
25.
Lynch SE, Ruiz de Castilla G., Williams RC, Kiritsy CP, Howell TH, Reddy MS, et al. (1991). The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. Periodontol62:458-467.
26.
Lyons KM, Pelton RW, Hogan BLM (1990). Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A). Development109:833-844.
27.
MacNeil RL, Somerman MJ (1993). Molecular factors regulating development and regeneration of cementum. J Periodont Res28:550-559.
28.
McCulloch CAG, Bordin S. (1991). Role of fibroblast subpopulations in periodontal physiology and pathology. J Periodont Res26:144-154.
29.
McPherron AC, Lee S.-J. (1993). Two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. ) Biol Chem268:3444-3449.
30.
Melcher AH (1976). On the repair potential of the periodontal tissues. J Periodontol47:256-260.
31.
Melcher AH, McCulloch CAG, Cheong T., Nemeth E., Shiga A. (1987). Cells from bone synthesize cementum-like and bony-like tissue in vitro and may migrate into periodontal ligament in vivo. J Periodont Res22:246-247.
32.
Mellonig JT (1992). Autogenous and allogeneic bone grafts in periodontal therapy. Crit Rev Oral Biol Med3:333-352.
33.
Minabe M. (1991). A critical review of the biologic rationale for guided tissue regeneration. ) Periodontol62:171-179.
34.
Nakashima M. (1990). The induction of reparative dentine in the amputated dental pulp of the dog by bone morphogenetic protein. Arch Oral Biol35:493-497.
35.
Nakashima M. (1994). Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix. Arch Oral Biol39:1085-1089.
36.
Nyman S., Lindhe J., Karring T., Rylander H. (1982). New attachment following surgical treatment of human periodontal disease. J Clin Periodontol9:290-296.
37.
Ozkaynak E., Rueger DC, Drier EA, Corbett C., Ridge RJ, Sampath TK, et al. (1990). OP-1 cDNA encodes an osteogenic protein in the TGF-β family. EMBO (Eur Mol Biol Org) J9:2085-2093.
38.
Ozkaynak E., Schnegelsberg PNJ, Oppermann H. (1991). Murine osteogenic protein (OP-1): High levels of mRNA in kidney. Biochem Biophys Res Commun179:116-123.
39.
Ozkaynak E., Schnegelsberg PN), Jin DF, Clifford GM, Warren FD, Drier EA, et al. (1992). Osteogenic protein-2. A new member of the transforming growth factor-β superfamily expressed early in embryogenesis. Biol Chem267:25220-25227.
40.
Padgett RW, St Johnston RD, Gelbart WM (1987). A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-beta family. Nature325:81-84.
41.
Park I.-B., Matsuura M., Han K.-Y., Norderyd O., Lin W.-L., Genco RJ, et al. (1995). Periodontal regeneration in class III furcation defects in beagle dogs using guided tissue regenerative therapy with platelet-derived growth factor. J Periodontol66:462-477.
42.
Pitaru S., McCulloch CAG, Narayanan SA (1994). Cellular origins and differentiation control mechanisms during periodontal development and wound healing. J Periodont Res29:81-94.
43.
Reddi AH (1974). Bone matrix in the solid state: Geometric influence on differentiation of fibroblasts. Adv Biol Med Phys15:1-18.
44.
Reddi AH (1981). Cell biology and biochemistry of endochondral bone development. Collagen Rel Res1:209-226.
45.
Reddi AH (1984). Extracellular matrix and development. In: Extracellular matrix biochemistry. Piez KA, Reddi AH, editors. New York: Elsevier, pp. 375-412.
46.
Reddi AH (1992). Regulation of cartilage and bone differentiation by bone morphogenetic proteins. Curr Opin Cell Biol4:850-855.
47.
Reddi AH (1994a). Symbiosis of biotechnology and biomaterials: Applications in tissue engineering of bone and cartilage. Cell Biochem56:192-195.
48.
Reddi AH (1994b). Bone and cartilage differentiation. Curr Opin Gen Dev4:737-744.
49.
Reddi AH (1996). BMP-1: Resurrection as procollagen C-proteinase. Science271:463.
50.
Reddi AH, Huggins CB (1972). Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci USA69:1601-1605.
51.
Reynolds MA, Bowers GM (1996). Fate of demineralized freeze-dried bone allografts in human intrabony defects. J Periodontol67:150-157.
52.
Ripamonti U., Reddi AH (1994). Periodontal regeneration: Potential role of bone morphogenetic proteins. J Periodont Res29:225-235.
53.
Ripamonti U., Vukicevic S. (1995). Bone morphogenetic proteins: From developmental biology to molecular therapeutics. S Afr J Sci91:277-280.
54.
Ripamonti U., Petit J.-C, Lemmer J., Austin JC (1987). Regeneration of the connective tissue attachment on surgically exposed roots using a fibrin-fibronectin adhesive system. An experimental study on the baboon (Papio ursinus). J Periodont Res22:320-326.
55.
Ripamonti U., Magan A., Ma S., van den Heever B., Moehl T., Reddi AH (1991). Xenogeneic osteogenin, a bone morphogenetic protein, and demineralized bone matrices, including human, induce bone differentiation in athymic rats and baboon. Matrix11:404-411.
56.
Ripamonti U., Ma S., Cunningham NS, Yeates L., Reddi AH (1992a). Initiation of bone regeneration in adult baboons by osteogenin, a bone morphogenetic protein. Matrix12:369-380.
57.
Ripamonti U., Ma S., Reddi AH (1992b). The critical role of geometry of porous hydroxyapatite delivery system in induction of bone by osteogenin, a bone morphogenetic protein. Matrix12:202-212.
58.
Ripamonti U., Heliotis M., van den Heever B., Reddi AH (1994). Bone morphogenetic proteins induce periodontal regeneration in the baboon (Papio ursinus). J Periodont Res29:439-445.
59.
Ripamonti U., Heliotis M., Rueger DC, Sampath TK (1996a). Induction of cementogenesis by recombinant human osteogenic protein-1 (hOP-1/BMP-7) in the baboon (Papio ursinus). Arch Oral Biol41:121-126.
60.
Ripamonti U., van den Heever B., Sampath TK, Tucker MM, Rueger DC, Reddi AH (1996b). Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7). Growth Factors13:1-17.
61.
Rutherford RB, Niekrash CE, Kennedy JE, Charette MF (1992). Platelet-derived and insulin-like growth factors stimulate regeneration of periodontal attachment in monkeys. J Periodont Res27:285-290.
62.
Rutherford RB, Ryan ME, Kennedy JE, Tucker MM, Charette MF (1993a). Platelet-derived growth factor and dexamethasone combined with collagen matrix induce regeneration of the periodontium in monkeys. J Clin Periodontol20:537-544.
63.
Rutherford RB, Wahle J., Tucker M., Rueger D., Charette M. (1993b). Induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1. Arch Oral Biol38:571-576.
64.
Sampath TK, Reddi AH (1981). Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. Proc Natl Acad Sci USA78:7599-7603.
65.
Sampath TK, Reddi AH (1983). Homology of bone-inductive proteins from human, monkey, bovine and rat extracellular matrix. Proc Natl Acad Sci USA80:6591-6595.
66.
Sampath TK, Reddi AH (1984). Importance of geometry of the extracellular matrix in endochondral bone differentiation. J Cell Biol98:2192-2197.
67.
Sampath TK, Maliakal JC, Hauschka PV, Jones WK, Sasak H., Tucker RF, et al. (1992). 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 Chem267:20352-20362.
68.
Sampath TK, Rashka KE, Doctor JS, Tucker RF, Hoffman FM (1993). Drosophila TGF-beta superfamily proteins induce endochondral bone formation in mammals. Proc Natl Acad Sci USA90:6004-6008.
69.
Selvig KA, Wikesjo UME, Bogle GC, Finkelman RD (1994). Impaired early bone formation in periodontal fenestration defects in dogs following application of insulin-like growth factor (II). Basic fibroblast growth factor and transforming growth factor beta 1. J Clin Periodontol21:380-385.
70.
Sigurdsson TJ Lee MB, Kubota K., Turek TJ, Wozney JM, Wikesjo UME (1995). Periodontal repair in dogs: Recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. J Periodontol66:131-138.
71.
ten Dijke P., Yamashita H., Sampath TK, Reddi AH, Estevez M., Riddle DL, et al. (1994). Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. I Biol Chem269:16985-16988.
72.
Terranova VP, Wikesjo UME (1987). Extracellular matrices and polypeptide growth factors as mediators of functions of cells of the periodontium. J Periodontol58:371-380.
73.
Terranova VP, lendresen M., Young F. (1989). Healing, regeneration, and repair: Prospectus for new dental treatment. Adv Dent Res3:69-79.
74.
Urist MR (1965). Bone: Formation by autoinduction. Science159:893-899.
75.
Vainio S., Karavanova I., Jowett A., Thesleff I. (1993). Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell75:45-58.
76.
van Eeden S., Ripamonti U. (1994). Bone differentiation in porous hydroxyapatite in baboons is regulated by the geometry of the substratum: Implications for reconstructive craniofacial surgery. Plast Reconstr Surg93:959-966.
77.
Vukicevic S., Latin V., Chen P., Batorsky R., Reddi AH, Sampath TK (1994a). Localization of osteogenic protein-1, a bone morphogenetic protein, during human embryonic development. Biochem Biophys Res Commun198:693-700.
78.
Vukicevic S., Helder MN, Luyten FP (1994b). Developing human lung and kidney are major sites for synthesis of bone morphogenetic protein-3 (osteogenin). J Histochem Cytochem42:869-875.
79.
Wang EA, Rosen V., D'Alessandro IS, Bauduy M., Cordes P., Harada T., et al. (1990). Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA87:2220-2224.
80.
Wharton KA, Thomsen GH, Gelbart WM (1991). Drosophila 60A gene, another transforming growth factor beta family member, is closely related to human bone morphogenetic proteins. Proc Natl Acad Sci USA88:9214-9218.
81.
Wikesjo UME, Claffey N., Christersson LA, Franzetti LC, Genco RJ, Terranova VP, et al. (1988). Repair of periodontal furcation defects in beagle dogs following reconstructive surgery including root surface demineralization with tetracycline hydrochloride and topical fibronectin application. J Clin Periodontol15:73-80.
82.
Wikesjo UME, Nilveus RE, Selvig KA (1992). Significance of early healing events on periodontal repair: A review. I Periodontol63:158-165.
83.
Wirthlin MR (1981). The current status of new attachment therapy. I Periodontol52:529-544.
84.
Wozney JM (1992). The bone morphogenetic protein family and osteogenesis. Molec Rep Dev32:160-167.
85.
Wozney JM (1995). The potential role of bone morphogenetic proteins in periodontal reconstruction. J Periodontol66:506-510.
86.
Wozney JM, Rosen V., Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, et al. (1988). Novel regulators of bone formation: Molecular clones and activities. Science242:1528-1534.
