Abstract
A lysyl-proline derivate (LP) known to stimulate angiogenesis and formation of granulation tissue was tested as a local additive to allogeneic demineralized bone matrix (DBM) using a rat craniotomy model. Peracetic-acid sterilized DBM (10 mg/defect) was implanted into three groups of 45 animals each with 0, 6 and 20 μg LP. Subsequent evaluation was done by descriptive histology, histomorphometry, and determination of the calcium content of the explants 7, 14, 28, 42 and 84 days post-implantation. Grafting with DBM alone resulted in defect bridging by newly formed bone with incorporated DBM residues on day 84. Addition of LP to the implants caused an enhanced capillarization on day 14 and 28 as well as an enhanced mineralization on day 14, 28, 42 and 84. Both effects were dose-dependent. These data suggest that the local application of a synthetic angiogenic factor significantly improve bone regeneration in DBM-grafted trephine defects in rats. Thereby, they reinforce the opinion that early angiogenesis is crucial for a number of subsequent events in the bone regeneration process.
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References cited
Boden SD (1999) Bioactive factors for bone tissue engineering. Clin Orthop 367 (Suppl): S 84–94
Borloo M andDe-Meester I (1994) Dipeptidyl peptidase IV: development, design, synthesis and biological evaluation of inhibitors. Verh K Acad Geneeskd Belg 56: 57–88
Buntrock P,Neubert K,Kohl A,Moch C,Born I,Demuth U andBarth A (1988) Stimulation and inhibition of the wound healing process using short-chain peptides. Biol Zent bl 107: 87–92
Cochran DL andWozney JM (1999) Biological mediators for periodontal regeneration. Periodontol-2000 19: 40–58
Deporter DA,Komori N,Howley TP,Shiga A,Ghent A,Hansel P andParisien K (1988) Calcif Tissue Int 42: 321–325
Feller AC,Radzun HJ,Heymann E,Haase H,Scholz W andParwaresch MR (1986) A monoclonal antibody detecting dipeptidylpeptidase IV in human tissue. Virchows Arch A Pathol Anat Histopathol 409: 263–273
Ferguson C,Alpern E,Miclau T andHelms JA (1999) Does adult fracture repair recapitulate embryonic skeletal formation? Mech Dev 87: 57–66
Fleischer B (1994) CD26: a surface protease involved in T-cell activation. Immunol Today 15: 180–184
Glowacki J (1998) Angiogenesis in fracture repair. Clin Orthop 355 (Suppl): S 82–89
Goldring SR andGoldring MB (1996) Cytokines and skeletal physiology. Clin Orthop 324: 13–23
Harada S,Nagy JA,Sullivan KA,Thomas KA,Endo N,Rodan GA andRodan SB (1994) Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. J Clin Invest 93: 2490–2496
Helm GA,Alden TD,Sheehan JP andKallmes D (2000) Bone morphogenetic proteins and bone morphogenetic gene therapy in neurological surgery: a review. Neurosurgery 46: 1213–1222
Joyce ME,Jingushi S,Scully SP andBolander ME (1991) Role of growth factors in fracture healing. Clinical and experimental approaches to dermal and epidermal repair: normal and chronic wounds. Prog Clin Biol Res 365: 391–416
Kohl A,Volk HD,Diezel W,Buntrock P andDiamantstein T (1989) The dipeptide lys-pro restores the diminished wound healing following treatment with anti-T-helper cell monoclonal antibody. Int J Immunopharmac 11: 237–240
Kohl A,Volk HD,Diezel W,Buntrock P,Diamantstein T andvon Baehr R (1991) The role of DPIV positive T-cells in wound healing and angiogenesis. Agents Actions 32: 125–127
Korom S,De-Meester I,Onodera K,Stadlbauer TH,Borloo M,Lambeir AM andKupiec-Weglinski JW (1997) The effects of CD26/DPP IV-targeted therapy on acute allograft rejection. Transplant Proc 29: 1274–1275
Lind M (1996) Growth factors: Possible new clinical tools. A review. Acta Orthop Scand 67: 407–417
Marden LJ, Fan RS, Pierce GF, Reddi AH and Hollinger JO (1993) Platelet-derived growth factor inhibits bone regeneration induced by osteogenin, a bone morphogenetic protein, in rat craniotomy defects. J Clin Invest 92: 2897–2905
Marquet D,Baggio L,Kobayashi T,Bernard AM,Pierres M,Nielsen PF,Ribel U,Watanabe T,Drucker DJ andWagtmann N (2000) Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA 97: 6874–6879
Nottebaert M,Lane JM,Juhn A,Burstein A,Schneider R,Klein C,Sinn RS,Dowling C,Cornell C andCatsimpoolas N (1989) Omental angiogenic lipid fraction factor and bone repair. An experimental study in the rat. J Orthop Res 7: 157–169
Pruss A,Kao M,Kiesewetter H,von Versen R andPauli G (1999) Virus safety of avital bone tissue transplants: Evaluation of sterilization steps of spongiosa cuboids using a peracetic acid-methanol mixture. Biologicals 27: 195–201
Rabie AB (1997) Vascular endothelial growth pattern during demineralized bone matrix induced osteogenesis. Connect Tissue Res 36: 337–345
Reddi AH andCunningham NS (1993) Initiation and promotion of bone differentiation by bone morphogenetic proteins. Bone Miner Res 8: 499–502
Reddi AH andHuggins C 1972) Biochemical sequences in the transformation of normal fibroblasts in aldolescent rat. Proc Natl Acad Sci U.S.A. 69: 1601–1605
Roth K andWenzelides K (1989) Das interaktive Bildverarbeitungssystem AMBA/R. Gegenbaurs Morphol Jahrb 135: 25–32
Schwarz N,Redl H,Schlag G,Schiesser A,Lintner F,Dinges HP andThurnher M (1989) The influence of fibrin sealant on demineralized bone matrix-dependent osteoinduction. Clin Orthop 238: 282–287
Urist MR (1965) Bone: Formation by autoinduction. Science 150: 893–899
Urist MR,DeLange RJ andFinerman GAM (1983) Bone cell differentiation and growth factors. Science 220: 680–686
Villanueva JE andNimni ME (1990) Promotion of calvarial cell osteogenesis by endothelial cells. J Bone Miner Res 5: 733–739
von Versen R,Denner K,Freistedt B,Sehrt B andMatthes G (1989) Verfahren zur Präparation demineralisierter Knochenmatrix. Z med Lab diagn 30: 154–158
Wang JS andAspenberg P (1993) Basic fibroblast growth factor and bone induction in rats. Acta Orthop Scand 64: 557–561
Wang J andGlimcher MJ (1999) Characterization of matrix-induced osteogenesis in rat calvarial bone defects: II. Origin of bone forming cells. Calcif Tissue Int 65: 486–493
Wang JS (1996) Basic fibroblast growth factor for stimulation of bone formation in osteoinductive or conductive implants. (Suppl 269) Acta Orthop Scand 67: 1–33
Weibel ER andElias H (1967) Quantitative methods of morphology. Springer Verlag, Berlin, Heidelberg, New York
Wozney JM andRosen V (1998) Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop 346: 26–37
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Hansen, A., Pruss, A., Gollnick, K. et al. Demineralized Bone Matrix-stimulated Bone Regeneration in Rats Enhanced by an Angiogenic Dipeptide Derivate. Cell Tissue Banking 2, 69–75 (2001). https://doi.org/10.1023/A:1014361206240
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DOI: https://doi.org/10.1023/A:1014361206240