title: Transforming growth factor-beta1 incorporated in calcium phosphate cement stimulates osteotransductivity in rat calvarial bone defects.
abstract: Bone regeneration of the alveolar crest around dental implants is an important factor in the success of implant use. Calcium phosphate cement can be used as a bone substitute and applied clinically as a paste to fill micro- and macroscopic bone defects. We have shown earlier that the intermixing of the recombinant human transforming growth factor-beta1 (rhTGF-beta1) in hardening calcium phosphate cement stimulated osteoblastic differentiation of rat primary bone cells in vitro. The aim of the present study was to examine whether the similar enrichment with rhTGF-beta1 affects the replacement of calcium phosphate cement by bone (osteotransduction) in calvarial critical size defects (csd) of adult rats. Two bone defects of 5 mm diameter were created bilaterally in each skull of 10 adult male rats. Both defects were filled with 53 mg of calcium phosphate cement without rhTGF-beta1 (control) at one side, and with 10 or 20 ng rhTGF-beta1 at the other side. After 8 weeks, defects with surrounding skull were analysed histologically and histomorphometrically. The addition of rhTGF-beta1 in the cement increased the amount of bone in rat skull defects. This finding coincidences with our in vitro observations, that intermixing of rhTGF-beta1 in calcium phosphate cement stimulates bone cell differentiation. Addition of rhTGF-beta1 stimulated bone formation as indicated by an increased bone volume of 50% and an increased bone/cement contact of 65%, in comparison to control defects with cement without rhTGF-beta1. In addition, rhTGF-beta1 reduced the remaining volume of cement, by 11% at 10 ng rhTGF-beta1, and by 20% at 20 ng rhTGF-beta1 in the cement. Defect closure was not affected. We conclude that the intermixing of rhTGF-beta1 in a fast-setting calcium phosphate cement stimulates bone growth and the osteotransduction of the cement. For bone regeneration procedures around endosseous implants, calcium phosphate cement with rhTGF-beta1 might be an appropriate combination for early osseointegration and implant use.
authors.affiliation: Dept. of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA)-Vrije University, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. e.blom.ocb.acta@med.vu.nl
authors.forename: E J
authors.initials: EJ
authors.lastname: Blom
authors.forename: J
authors.initials: J
authors.lastname: Klein-Nulend
authors.forename: L
authors.initials: L
authors.lastname: Yin
authors.forename: M A
authors.initials: MA
authors.lastname: van Waas
authors.forename: E H
authors.initials: EH
authors.lastname: Burger
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000737:chemistry*; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes; D002130:Calcium Phosphates; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull / Q000601:surgery; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D001843:Bone Cements; D018786:Bone Substitutes; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous