Transforming growth factor-bgr1 incorporated in calcium phosphate cement stimulates osteotransductivity in rat calvarial bone defects

Authors: Blom E.J.1, 2; Klein-Nulend J.1; Burger E.H.1; van Waas M.A.J.2; Yin L.3

Source: Clinical Oral Implants Research, Volume 12, Number 6, 1 December 2001 , pp. 609-616(8)

Publisher: Blackwell Publishing

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Abstract:

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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-bgr1 (rhTGF-bgr1) 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-bgr1 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-bgr1 (control) at one side, and with 10 or 20 ng rhTGF-bgr1 at the other side. After 8 weeks, defects with surrounding skull were analysed histologically and histomorphometrically. The addition of rhTGF-bgr1 in the cement increased the amount of bone in rat skull defects. This finding coincidences with our in vitro observations, that intermixing of rhTGF-bgr1 in calcium phosphate cement stimulates bone cell differentiation. Addition of rhTGF-bgr1 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-bgr1. In addition, rhTGF-bgr1 reduced the remaining volume of cement, by 11% at 10 ng rhTGF-bgr1, and by 20% at 20 ng rhTGF-bgr1 in the cement. Defect closure was not affected. We conclude that the intermixing of rhTGF-bgr1 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-bgr1 might be an appropriate combination for early osseointegration and implant use.

Keywords: calcium phosphate cement; transforming growth factor-1; bone growth; rat skull defect

Document Type: Original article

Affiliations: 1: Dept. of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Vrije University, Amsterdam. 2: Dept. of Oral Function, Academic Centre for Dentistry Amsterdam (ACTA), Vrije University, Amsterdam, The Netherlands. 3: School of Dental and Oral Surgery, Columbia University, New York, NY, USA

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