Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates

Ulf M E Wikesjö, Yi Hao Huang, Andreas V. Xiropaidis, Rachel G. Sorensen, Michael D. Rohrer, Hari S. Prasad, John M. Wozney, Jan Hall

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. Material and Methods: rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. Results: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone-implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone-implant contact (∼75%; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density. Conclusion: rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval.

Original languageEnglish (US)
Pages (from-to)992-1000
Number of pages9
JournalJournal of Clinical Periodontology
Volume35
Issue number11
DOIs
StatePublished - Nov 1 2008

Fingerprint

Maxilla
Titanium
Osteogenesis
Primates
Bone and Bones
Osseointegration
Jaw
recombinant human bone morphogenetic protein-2
Macaca fascicularis
Population Groups
Bone Density
titanium dioxide
Canidae
Young Adult
Rodentia

Keywords

  • Bone morphogenetic protein
  • Dental/oral implants
  • Non-human primates
  • Osseointegration
  • Tissue engineering
  • Titanium
  • Titanium porous oxide
  • rhBMP-2

ASJC Scopus subject areas

  • Periodontics

Cite this

Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates. / Wikesjö, Ulf M E; Huang, Yi Hao; Xiropaidis, Andreas V.; Sorensen, Rachel G.; Rohrer, Michael D.; Prasad, Hari S.; Wozney, John M.; Hall, Jan.

In: Journal of Clinical Periodontology, Vol. 35, No. 11, 01.11.2008, p. 992-1000.

Research output: Contribution to journalArticle

Wikesjö, Ulf M E ; Huang, Yi Hao ; Xiropaidis, Andreas V. ; Sorensen, Rachel G. ; Rohrer, Michael D. ; Prasad, Hari S. ; Wozney, John M. ; Hall, Jan. / Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates. In: Journal of Clinical Periodontology. 2008 ; Vol. 35, No. 11. pp. 992-1000.
@article{b6d40bf7c8c6424baaad652d98f6bff6,
title = "Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates",
abstract = "Background: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. Material and Methods: rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. Results: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone-implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43{\%} and rhBMP-2 (0.2 mg/ml): 37{\%}. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone-implant contact (∼75{\%}; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density. Conclusion: rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval.",
keywords = "Bone morphogenetic protein, Dental/oral implants, Non-human primates, Osseointegration, Tissue engineering, Titanium, Titanium porous oxide, rhBMP-2",
author = "Wikesj{\"o}, {Ulf M E} and Huang, {Yi Hao} and Xiropaidis, {Andreas V.} and Sorensen, {Rachel G.} and Rohrer, {Michael D.} and Prasad, {Hari S.} and Wozney, {John M.} and Jan Hall",
year = "2008",
month = "11",
day = "1",
doi = "10.1111/j.1600-051X.2008.01322.x",
language = "English (US)",
volume = "35",
pages = "992--1000",
journal = "Journal of Clinical Periodontology",
issn = "0303-6979",
publisher = "Blackwell Munksgaard",
number = "11",

}

TY - JOUR

T1 - Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates

AU - Wikesjö, Ulf M E

AU - Huang, Yi Hao

AU - Xiropaidis, Andreas V.

AU - Sorensen, Rachel G.

AU - Rohrer, Michael D.

AU - Prasad, Hari S.

AU - Wozney, John M.

AU - Hall, Jan

PY - 2008/11/1

Y1 - 2008/11/1

N2 - Background: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. Material and Methods: rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. Results: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone-implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone-implant contact (∼75%; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density. Conclusion: rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval.

AB - Background: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. Material and Methods: rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. Results: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone-implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone-implant contact (∼75%; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density. Conclusion: rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval.

KW - Bone morphogenetic protein

KW - Dental/oral implants

KW - Non-human primates

KW - Osseointegration

KW - Tissue engineering

KW - Titanium

KW - Titanium porous oxide

KW - rhBMP-2

UR - http://www.scopus.com/inward/record.url?scp=54049138432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54049138432&partnerID=8YFLogxK

U2 - 10.1111/j.1600-051X.2008.01322.x

DO - 10.1111/j.1600-051X.2008.01322.x

M3 - Article

VL - 35

SP - 992

EP - 1000

JO - Journal of Clinical Periodontology

JF - Journal of Clinical Periodontology

SN - 0303-6979

IS - 11

ER -