Implant-guided vertical bone growth in the mini-pig Martin Freilich Bo Wen David Shafer Peter Schleier Michel Dard David Pendrys Denise Ortiz Liisa Kuhn Authors’ affiliations: Martin Freilich, Liisa Kuhn, Bo Wen, Denise Ortiz, Department of Reconstructive Sciences, Center for Biomaterials, School of Dental Medicine, University of Connecticut, Farmington, CT, USA David Shafer, Department of Craniofacial Sciences, Division of Oral & Maxillofacial Surgery, School of Dental Medicine, University of Connecticut, Farmington, Ct, USA David Pendrys, Department of Reconstructive Sciences, School of Dental Medicine, University of Connecticut, Farmington, CT, USA Peter Schleier, Oralfacial Surgery Section, Clinic for Special Medicine, Stavanger, Norway Michel Dard, Institut Straumann, Basel, Switzerland Corresponding author: Dr Martin Freilich Department of Reconstructive Sciences School of Dental Medicine University of Connecticut 263 Farmington Avenue Farmington CT USA Tel.: 860 679 2649 Fax: 860 679 1370 e-mail: [email protected]Key words: biomaterial scaffold, ng/rhBMP-2, scaffold retainer, vertical supracrestal bone growth Abstract Objective: To attain and describe guided vertical bone regeneration around titanium (Ti) and titanium zirconium (Ti–Zr) dental implants utilizing non-glycosylated recombinant human bone morphogenetic protein-2 (ng/rhBMP-2), biomaterial scaffolds and a scaffold retainer. Materials and methods: Thirty-two modified Straumann TE implants were partially embedded in the mandibles of eight adult mini-pigs. Pre-shaped resorbable scaffolds were placed around the implant and shielded and stabilized with a newly developed Ti custom scaffold retainer (umbrella) or wide-neck (WN) healing caps to stabilize the scaffold. Ng/rhBMP-2 (50 mg) was applied to the supracrestal portion of the implant or incorporated within the scaffold. At 9 weeks, soft tissue healing was assessed. Vertical bone regeneration outcomes including bone height, bone-to-implant contact (BIC) and bone volume were assessed by micro-computed tomography and histology. Results: Soft tissue healing at the test sites ( þ ng/rhBMP-2/ þ scaffold) appeared to be substantially better than the control sites ( ng/rhBMP-2/ scaffold). Bone height, BIC percentage and bone volume were all similar regardless of whether WN healing caps or umbrella scaffold stabilization was used for all biomaterial scaffolds tested. WN healing cap test sites showed greater new bone height and BIC as compared with aggregate data from the control sites (P ¼ 0.05). Comparison of aggregate data from the umbrella test sites showed greater BIC and new bone volume as compared with aggregate data from the control sites(P ¼ 0.05). Conclusion: Vertical bone regeneration was successfully attained utilizing ng/rhBMP-2, biomaterial scaffolds and a scaffold retainer. Current clinical methods for increasing vertical bone height include grafting from intra- and extra-oral sites and distraction osteogenesis. A successful outcome is site dependent and gener- ally associated with substantial levels of morbid- ity (Feichtinger et al. 2007). The overall goal of the study described here is to use dental implants, implant components and osteoinductive factors to guide a new layer of bone height while mini- mizing the technique sensitivity, risks and pro- blems seen with current clinical methods. The development of methods to predictably regener- ate 2–3 mm of additional bone height of good density and width would have important clinical implications at both anterior and posterior sites. The simultaneous placement of a partially in- serted dental implant, an inductive agent and a resorbable three-dimensional scaffold has been attempted to treat the vertical defect in experimen- tal dog/large animal models with varying degrees of success (Jovanovic et al. 1995; Renvert et al. 1996; Sigurdsson et al. 1997; Roos-Jansa ˚ker et al. 2002). For this approach, inductive agents have included allograft materials (Jung et al. 2008) or growth factors such as bone morphogenetic pro- tein-2 (BMP-2). A demineralized bone matrix (DBM) allograft has osteoinductive qualities and can serve as the three-dimensional scaffold to support new tissue growth. DBM is able to maintain space for bone growth, exhibit a framework for cell and matrix protein adhesion, and has the potential to deliver osteogenic cell signaling agents. The osteoinduc- tive value of DBM was recognized almost four decades ago after its placement into muscle pouches of animals and the subsequent formation of ectopic bone (Urist 1965; Lindholm et al. 1988). It has been shown that the osteogenic components Date: Accepted 14 March 2011 To cite this article: Freilich M, Wen B, Shafer D, Schleier P, Dard M, Pendrys D, Ortiz D, Kuhn L. Implant guided vertical bone growth in the mini-pig. Clin. Oral Impl. Res. xx, 2011; 000–000 doi: 10.1111/j.1600-0501.2011.02199.x c 2011 John Wiley & Sons A/S 1
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Implant-guided vertical bone growth inthe mini-pig
Martin FreilichBo WenDavid ShaferPeter SchleierMichel DardDavid PendrysDenise OrtizLiisa Kuhn
Authors’ affiliations:Martin Freilich, Liisa Kuhn, Bo Wen, Denise Ortiz,Department of Reconstructive Sciences, Center forBiomaterials, School of Dental Medicine, University ofConnecticut, Farmington, CT, USADavid Shafer, Department of Craniofacial Sciences,Division of Oral & Maxillofacial Surgery, School ofDental Medicine, University of Connecticut,Farmington, Ct, USADavid Pendrys, Department of ReconstructiveSciences, School of Dental Medicine, University ofConnecticut, Farmington, CT, USAPeter Schleier, Oralfacial Surgery Section, Clinic forSpecial Medicine, Stavanger, NorwayMichel Dard, Institut Straumann, Basel, Switzerland
Corresponding author:Dr Martin FreilichDepartment of Reconstructive SciencesSchool of Dental MedicineUniversity of Connecticut263 Farmington AvenueFarmingtonCT USATel.: 860 679 2649Fax: 860 679 1370e-mail: [email protected]
Objective: To attain and describe guided vertical bone regeneration around titanium (Ti) and titanium
zirconium (Ti–Zr) dental implants utilizing non-glycosylated recombinant human bone morphogenetic
protein-2 (ng/rhBMP-2), biomaterial scaffolds and a scaffold retainer.
Materials and methods: Thirty-two modified Straumann TE implants were partially embedded in the
mandibles of eight adult mini-pigs. Pre-shaped resorbable scaffolds were placed around the implant and
shielded and stabilized with a newly developed Ti custom scaffold retainer (umbrella) or wide-neck (WN)
healing caps to stabilize the scaffold. Ng/rhBMP-2 (50mg) was applied to the supracrestal portion of the
implant or incorporated within the scaffold. At 9 weeks, soft tissue healing was assessed. Vertical bone
regeneration outcomes including bone height, bone-to-implant contact (BIC) and bone volume were
assessed by micro-computed tomography and histology.
Results: Soft tissue healing at the test sites (þng/rhBMP-2/þ scaffold) appeared to be substantially
better than the control sites (�ng/rhBMP-2/� scaffold). Bone height, BIC percentage and bone volume
were all similar regardless of whether WN healing caps or umbrella scaffold stabilization was used for all
biomaterial scaffolds tested. WN healing cap test sites showed greater new bone height and BIC as
compared with aggregate data from the control sites (P¼ 0.05). Comparison of aggregate data from the
umbrella test sites showed greater BIC and new bone volume as compared with aggregate data from the
control sites(P¼ 0.05).
Conclusion: Vertical bone regeneration was successfully attained utilizing ng/rhBMP-2, biomaterial
scaffolds and a scaffold retainer.
Current clinical methods for increasing vertical
bone height include grafting from intra- and
extra-oral sites and distraction osteogenesis. A
successful outcome is site dependent and gener-
ally associated with substantial levels of morbid-
ity (Feichtinger et al. 2007). The overall goal of
the study described here is to use dental implants,
implant components and osteoinductive factors
to guide a new layer of bone height while mini-
mizing the technique sensitivity, risks and pro-
blems seen with current clinical methods. The
development of methods to predictably regener-
ate 2–3 mm of additional bone height of good
density and width would have important clinical
implications at both anterior and posterior sites.
The simultaneous placement of a partially in-
serted dental implant, an inductive agent and a
resorbable three-dimensional scaffold has been
attempted to treat the vertical defect in experimen-
tal dog/large animal models with varying degrees
of success (Jovanovic et al. 1995; Renvert et al.
1996; Sigurdsson et al. 1997; Roos-Jansaker et al.
2002). For this approach, inductive agents have
included allograft materials (Jung et al. 2008) or
growth factors such as bone morphogenetic pro-
tein-2 (BMP-2).
A demineralized bone matrix (DBM) allograft
has osteoinductive qualities and can serve as the
three-dimensional scaffold to support new tissue
growth. DBM is able to maintain space for bone
growth, exhibit a framework for cell and matrix
protein adhesion, and has the potential to deliver
osteogenic cell signaling agents. The osteoinduc-
tive value of DBM was recognized almost four
decades ago after its placement into muscle
pouches of animals and the subsequent formation
of ectopic bone (Urist 1965; Lindholm et al. 1988).
It has been shown that the osteogenic components
Date:Accepted 14 March 2011
To cite this article:Freilich M, Wen B, Shafer D, Schleier P, Dard M, Pendrys D,Ortiz D, Kuhn L. Implant guided vertical bone growth in themini-pig.Clin. Oral Impl. Res. xx, 2011; 000–000doi: 10.1111/j.1600-0501.2011.02199.x