Abstract
The association of a biodegradable material and a growth factor could be of clinical value for treating bone defects. We therefore tested the association of transforming growth factor β (TGF-β1) in fibrin glue and coral granules to heal skull defects in rabbits. Adult rabbits underwent a double trepanation symmetrically in both parietal bones. Using histomorphometry, we compared bone repair after 1 month in control animals (n=5) and in animals treated with either TGF-β1 as a single injection of 1 μg in methylcellulose (n=5) or in fibrin glue (n=5), or with coral granules in fibrin glue (n=4) or with coral granules and TGF-β1 1 μg in fibrin glue (n=5). We measured the diameter of the remaining defect and the surface of the bone growth. TGF-β1 without coral in either methyl cellulose or fibrin induced a partial closure of the defect as assessed by a significant decrease in the defect diameter, compared with the control group. However, the association of TGF-β1 in fibrin and coral induced an area of the bone growth higher than in any other groups (P<0.05). Two months after surgery, this triple association induced a better healing of the defect than coral alone or control group. In each group treated with TGF-β1, the mineralization rate was increased not only at the treated side but also in the contralateral defect which was untreated, suggesting a diffusion of the growth factor. Indeed, when pooled together, the diameter of the defect at the contralateral side of 14 animals that had received TGF-β1 was reduced compared with the control group. Significant coral granules resorption occurred between month 1 and 2 and was unchanged by the addition of TGF-β1. In conclusion, the triple association of coral granules and TGF-β1 in fibrin could be of interest for treating bone defects.
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References
Bentz H, Nathan RM, Rosen DM, Armstrong RM, Thompson AY, Segarini PR, Mathews MC, Dasch JR, Piez KA, Seyedin SM (1989) Purification and characterization of a unique osteoinductive factor from bovine bone. J Biol Chem 264:20805–20810
Reddi AH (1985) Regulation of bone differentiation by local and systemic factors. In: Peck WA (ed) Bone and mineral research, vol. 3. Elsevier, Amsterdam, pp 27–47
Luyten FP, Cunningham NS, Ma S, Muthukumaran N, Ttammonds RG, Nevins WB, Wood WI, Reddi AH (1989) Purification and partial amino-acid sequence of osteogenin, a protein initiating bone differentiation. J Biol Chem 264:13377
Maryuart T, Lioubin MN, Keda TT (1987) Complete amino acid sequence of human transforming growth factor type β2. J Biol Chem 262:12127–12131
Sporn MB, Roberts AB (1989) Transforming growth factor-β. Multiple actions and potential clinical applications. JAMA 262(7):938–941
Horisaka Y, Okamoto Y, Matsumoto N, Yoshimura Y, Kawada J, Yawada K, Takagi T (1991) Subperiosteal implantation of bone morphogenetic protein adsorbed to hydroxyapatite. Clin Orthop Rel Res 268:303–312
Katz RW, Felthousen GC, Reddi ATT (1990) Radiationsterilized insoluble collagenous bone matrix is a functional carrier of osteogenin for bone induction. Calcif Tissue Int 47:183–185
Ripamonti U, Shu-Shan M (1993) Reconstruction of bone marrow organ by osteogenin, a bone morphogenetic protein and demineralized bone matrix in calvarial defects of adult primates. Plast Reconstr Surg 91:27–33
Cohen-Solal M, Morieux C, de Vernejoul MC (1991) Relationship between the number of resorbing cells and the amount resorbed in metabolic bone disorders. J Bone Miner Res 6:915–920
Beck SL, Deguzman L, Wyne PL, Xu Y, McFatridge LA, Gillet N, Amento EP (1991) TGF-β1 induces bone closure of skull defect. J Bone Miner Res 6:1257–1265
Beck SL, Amento EP, Xu Y, Deguzman L, Lee WP, Nguyen T, Gillett NA (1993) TGF-β1 induces bone closure of skull defects: temporal dynamics of bone formation in defect exposed to rhTGF-β1. J Bone Miner Res 8:753–761
Guillemin G, Patat JL, Fournié J, Chetail M (1987) The use of coral as a bone graft substitute. J Biomed Mat Res 21:557–567
Hott M, Marie PJ, Guillemin G Patat JL (1991) Osteoinductive effect of coral implanted in rat bone marrow. In: Vincenzini P (ed) Ceramics in substitutive and reconstructive surgery. Elsevier Science Publishers, New York, pp 345–352
Roux FX, Brasnu D, Loty B, George B, Guillemin G (1988) Madreporic coral: a new bone graft substitute for cranial surgery. J Neurosurg 69(4):510–513
Ouhayoun JP, Shabana AHM, Tssakian S, Patat JL, Guillemin G, Sawaf MH, Forest N (1992) Histological evaluation of natural coral skeleton as a grafting material in miniature swine mandible. J Mater Sci Med 3:222–228
Kawamura M, Urist MR (1988) Induction of callus formation by implants of bone morphogenetic protein and associated bone matrix noncollagenous proteins. Clin Orthop Rel Res 236:240–248
Hock JM, Canalis E, Centrella M (1990) Transforming growth factor-β stimulates bone matrix apposition and bone cell replication in cultured fetal rat calvariae. Endocrinology 126(1):421–426
Joyce ME, Roberts AB, Sporn MB, Bolander ME (1990) Transforming growth factor-β and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol 110:2195–2207
Marcelli C, Yates AJ, Mundy GR (1990) In vivo effects of human recombinant transforming growth factor β on bone turnover in normal mice. J Bone Miner Res 5:1087–1096
Noda M, Camillière JJ (1989) In vivo stimulation of bone formation by transforming growth factor beta. Endocrinology 124(6):2991–2994
Takagi K, Urist MR (1982) The reaction of the dura to bone morphogenetic protein (BMP) in repair of the skull defects. Ann Surg 196(1):100–109
Ferguson D, Davis WL, Urist MR, Hurt WC, Allen EP (1987) Bovine bone morphogenetic protein (bBMP) fraction induced repair of craniotomy defects in the rhesus monkey (Macara speciosa). Clin Orthop Rel Res 219:251–258
Doll BA, Towle HJ, Hollinger JO, Reddi AH, Mellonig JT (1990) The osteogenic potential of two composite graft systems using osteogenin. J Periodontol 61(12): 745–750
Courpied JP, Deplus P, Barthas J, Forest M, Carlioz A, Vacher-Lachenu MC, Crouzette J, Fournier P, Baufume M (1982) Les bioverres et le tissu osseux: etude expérimentale. Int Orthop 6:1–7
Tsunawaki S, Sporn M, Ding A, Nathan C (1988) Dectivation of macrophages by transforming growth factor-β. Nature 334: 260–262
Frost HM (1989) The biology of fracture healing: an overview for clinicians. Part 1 and 11. Clin Orthop Rel Res 248:283–309
Mueller M, Schilling T, Minne HW, Ziegle RA (1991) Systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenomenon (RAP) during healing of a bone defect in the rat. J Bone Miner Res 6(4):401–410
Einhorn TA, Simon G, Devlin VJ, Warman J, Sidhu SPS, Vigorita VJ (1990) The osteogenic response to distant skeletal injury. J Bone Joint Surg 72-A(9):1374–1378
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Arnaud, E., Morieux, C., Wybier, M. et al. Potentiation of transforming growth factor (TGF-β1) by natural coral and fibrin in a rabbit cranioplasty model. Calcif Tissue Int 54, 493–498 (1994). https://doi.org/10.1007/BF00334331
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DOI: https://doi.org/10.1007/BF00334331