Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration

Knut A. Selvig, Rachel G. Sorensen, John M. Wozney, Ulf M E Wikesjö

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable sponge (ACS) carrier is currently being evaluated as candidate therapy for periodontal regeneration. The objective of this study was to characterize, in some detail, tissue reactions following surgical implantation of rhBMP-2/ACS into periodontal defects. Methods: Four young adult, male beagle dogs with surgically induced, bilateral, critical size, supraalveolar, mandibular premolar defects sequentially received rhBMP-2/ACS (rhBMP-2 at 0.2 mg/ml) in right and left jaw quadrants. After 4 or 8 weeks of healing, experimental teeth with surrounding tissues were harvested and processed for light and transmission electron microscopy. Results: Surgical implantation of rhBMP-2/ACS into large supraalveolar periodontal defects resulted in a variable tissue response without marked difference between 4- and 8-week observations. New bone, exceeding the volume of the normal alveolar process, had formed within 4 weeks. The regenerated bone tissue consisted of finely trabeculated woven bone. Marrow spaces exhibited a continuous lining of osteoblasts, osteoclasts, and resting cells. The marrow spaces contained numerous large, thin-walled vessels but were almost devoid of collagen fibrils or fibroblasts. Large voids (seromas) encountered in the newly formed bone were free of structured elements except for occasional aggregates of effete erythrocytes. A variety of tissue reactions were observed along the root surface including areas of resorption, areas of hard tissue deposition, and areas without resorptive or appositional activity. Ankylosis was a frequent observation, although areas showing characteristics of a periodontal ligament with a fine layer of acellular fiber cementum and occasional inserting Sharpey's fibers were also observed. Osteoblasts facing the root surface often appeared to be in a highly active state judged by their cuboidal shape, well-developed endoplasmic reticulum and numerous mitochondria, and the presence of an adjacent layer of preosteoblasts. Conspicuous bundles of wide collagen fibrils near the dentin surface as well as within the marrow spaces were considered to represent remnants of the ACS. These fibrils were associated with areas of mineralization as verified by examination of undecalcified specimens. Conclusions: rhBMP-2/ACS elicits a rapid osteoinductive process throughout the implant as well as along and onto the instrumented adjacent root surface. Lamellated trabecular bone was the predominant regenerated tissue. A typical cementum-periodontal ligament-alveolar bone relationship was a rare observation. The great variability in histological tissue response along the instrumented root surface indicates that the stimulus to hard tissue formation resided primarily in the rhBMP-2/ACS implant rather than in the root surface.

Original languageEnglish (US)
Pages (from-to)1020-1029
Number of pages10
JournalJournal of periodontology
Volume73
Issue number9
DOIs
StatePublished - Sep 1 2002

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Regeneration
Bone and Bones
Dental Cementum
Periodontal Ligament
Bone Marrow
Osteoblasts
Collagen
Observation
Seroma
Alveolar Process
Ankylosis
recombinant human bone morphogenetic protein-2
Bicuspid
Porifera
Osteoclasts
Dentin
Jaw
Transmission Electron Microscopy
Endoplasmic Reticulum
Young Adult

Keywords

  • Alveolar bone loss/therapy
  • Animal studies
  • Ankylosis
  • Bone morphogenetic
  • Collagen/therapeutic use
  • Dental cementum/growth and development
  • Osteogenesis
  • Periodontal ligament
  • Proteins
  • Tooth resorption
  • Tooth root

ASJC Scopus subject areas

  • Periodontics

Cite this

Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration. / Selvig, Knut A.; Sorensen, Rachel G.; Wozney, John M.; Wikesjö, Ulf M E.

In: Journal of periodontology, Vol. 73, No. 9, 01.09.2002, p. 1020-1029.

Research output: Contribution to journalArticle

Selvig, Knut A. ; Sorensen, Rachel G. ; Wozney, John M. ; Wikesjö, Ulf M E. / Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration. In: Journal of periodontology. 2002 ; Vol. 73, No. 9. pp. 1020-1029.
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AU - Sorensen, Rachel G.

AU - Wozney, John M.

AU - Wikesjö, Ulf M E

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N2 - Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable sponge (ACS) carrier is currently being evaluated as candidate therapy for periodontal regeneration. The objective of this study was to characterize, in some detail, tissue reactions following surgical implantation of rhBMP-2/ACS into periodontal defects. Methods: Four young adult, male beagle dogs with surgically induced, bilateral, critical size, supraalveolar, mandibular premolar defects sequentially received rhBMP-2/ACS (rhBMP-2 at 0.2 mg/ml) in right and left jaw quadrants. After 4 or 8 weeks of healing, experimental teeth with surrounding tissues were harvested and processed for light and transmission electron microscopy. Results: Surgical implantation of rhBMP-2/ACS into large supraalveolar periodontal defects resulted in a variable tissue response without marked difference between 4- and 8-week observations. New bone, exceeding the volume of the normal alveolar process, had formed within 4 weeks. The regenerated bone tissue consisted of finely trabeculated woven bone. Marrow spaces exhibited a continuous lining of osteoblasts, osteoclasts, and resting cells. The marrow spaces contained numerous large, thin-walled vessels but were almost devoid of collagen fibrils or fibroblasts. Large voids (seromas) encountered in the newly formed bone were free of structured elements except for occasional aggregates of effete erythrocytes. A variety of tissue reactions were observed along the root surface including areas of resorption, areas of hard tissue deposition, and areas without resorptive or appositional activity. Ankylosis was a frequent observation, although areas showing characteristics of a periodontal ligament with a fine layer of acellular fiber cementum and occasional inserting Sharpey's fibers were also observed. Osteoblasts facing the root surface often appeared to be in a highly active state judged by their cuboidal shape, well-developed endoplasmic reticulum and numerous mitochondria, and the presence of an adjacent layer of preosteoblasts. Conspicuous bundles of wide collagen fibrils near the dentin surface as well as within the marrow spaces were considered to represent remnants of the ACS. These fibrils were associated with areas of mineralization as verified by examination of undecalcified specimens. Conclusions: rhBMP-2/ACS elicits a rapid osteoinductive process throughout the implant as well as along and onto the instrumented adjacent root surface. Lamellated trabecular bone was the predominant regenerated tissue. A typical cementum-periodontal ligament-alveolar bone relationship was a rare observation. The great variability in histological tissue response along the instrumented root surface indicates that the stimulus to hard tissue formation resided primarily in the rhBMP-2/ACS implant rather than in the root surface.

AB - Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable sponge (ACS) carrier is currently being evaluated as candidate therapy for periodontal regeneration. The objective of this study was to characterize, in some detail, tissue reactions following surgical implantation of rhBMP-2/ACS into periodontal defects. Methods: Four young adult, male beagle dogs with surgically induced, bilateral, critical size, supraalveolar, mandibular premolar defects sequentially received rhBMP-2/ACS (rhBMP-2 at 0.2 mg/ml) in right and left jaw quadrants. After 4 or 8 weeks of healing, experimental teeth with surrounding tissues were harvested and processed for light and transmission electron microscopy. Results: Surgical implantation of rhBMP-2/ACS into large supraalveolar periodontal defects resulted in a variable tissue response without marked difference between 4- and 8-week observations. New bone, exceeding the volume of the normal alveolar process, had formed within 4 weeks. The regenerated bone tissue consisted of finely trabeculated woven bone. Marrow spaces exhibited a continuous lining of osteoblasts, osteoclasts, and resting cells. The marrow spaces contained numerous large, thin-walled vessels but were almost devoid of collagen fibrils or fibroblasts. Large voids (seromas) encountered in the newly formed bone were free of structured elements except for occasional aggregates of effete erythrocytes. A variety of tissue reactions were observed along the root surface including areas of resorption, areas of hard tissue deposition, and areas without resorptive or appositional activity. Ankylosis was a frequent observation, although areas showing characteristics of a periodontal ligament with a fine layer of acellular fiber cementum and occasional inserting Sharpey's fibers were also observed. Osteoblasts facing the root surface often appeared to be in a highly active state judged by their cuboidal shape, well-developed endoplasmic reticulum and numerous mitochondria, and the presence of an adjacent layer of preosteoblasts. Conspicuous bundles of wide collagen fibrils near the dentin surface as well as within the marrow spaces were considered to represent remnants of the ACS. These fibrils were associated with areas of mineralization as verified by examination of undecalcified specimens. Conclusions: rhBMP-2/ACS elicits a rapid osteoinductive process throughout the implant as well as along and onto the instrumented adjacent root surface. Lamellated trabecular bone was the predominant regenerated tissue. A typical cementum-periodontal ligament-alveolar bone relationship was a rare observation. The great variability in histological tissue response along the instrumented root surface indicates that the stimulus to hard tissue formation resided primarily in the rhBMP-2/ACS implant rather than in the root surface.

KW - Alveolar bone loss/therapy

KW - Animal studies

KW - Ankylosis

KW - Bone morphogenetic

KW - Collagen/therapeutic use

KW - Dental cementum/growth and development

KW - Osteogenesis

KW - Periodontal ligament

KW - Proteins

KW - Tooth resorption

KW - Tooth root

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