A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration

Andreas Stavropoulos, Peter Windisch, Istvan Gera, Björn Capsius, Anton Sculean, Ulf M E Wikesjö

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Aim The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier rhGDF-5/β-TCP into periodontal defects in man. Material & Methods Twenty chronic periodontitis patients, each with at least one tooth scheduled for extraction exhibiting a probing depth ≥6 mm and an associated intra-bony defect ≥4 mm participated in the study upon written informed consent. Subjects (one defect/patient) were randomized to receive open flap debridement (OFD) + rhGDF-5/β-TCP (n = 10) or OFD alone (control; n = 10). Block biopsies of the defect sites were collected at 6 months post-surgery and prepared for the histological evaluation. Two masked examiners evaluated the deepest aspect of each defect site relative to bone (height/area), periodontal ligament (PDL) and cementum regeneration, and residual β-TCP. Results Sites receiving rhGDF-5/β-TCP showed numerically greater PD reduction (3.7 ± 1.2 versus 3.1 ± 1.8 mm; p = 0.26), less gingival recession (0.5 ± 0.8 versus 1.4 ± 1.0 mm; p < 0.05) and greater clinical attachment level (CAL) gain (3.2 ± 1.7 versus 1.7 ± 2.2 mm; p = 0.14) at the deepest aspect of the defect compared with OFD alone. One biopsy in the rhGDF-5/β-TCP and four biopsies in the OFD group were deemed as not evaluable. Histologically, bone regeneration height was almost threefold greater for the rhGDF-5/β-TCP treatment compared with OFD alone (2.19 ± 1.59 versus 0.81 ± 1.02 mm; p = 0.08). Similarly an almost twofold increase was observed for PDL (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26), cementum (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26) and bone regeneration area (0.74 ± 0.69 versus 0.32 ± 0.47 mm 2; p = 0.14). Root resorption/ankylosis was not observed. Residual β-TCP occupied 8.4 ± 11.5% of the area of interest in biopsies of patients receiving rhGDF-5/β-TCP. Five biopsies (one rhGDF-5/β-TCP, four OFD) were deemed unsuitable to allow a meaningful histological or histometrical evaluation. Conclusions Descriptive statistics showed greater PD reduction and CAL gain, and greater alveolar bone regeneration and periodontal regeneration at sites that received rhGDF-5/β-TCP compared to control. However, these differences were not statistically significant. Future studies with larger sample sizes will have to be conducted to verify these findings.

Original languageEnglish (US)
Pages (from-to)1044-1054
Number of pages11
JournalJournal of Clinical Periodontology
Volume38
Issue number11
DOIs
StatePublished - Nov 1 2011

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Regeneration
Debridement
Bone Regeneration
Biopsy
Dental Cementum
Periodontal Ligament
Phosphate Transport Proteins
Gingival Recession
Root Resorption
human GDF5 protein
Ankylosis
Chronic Periodontitis
Tooth Extraction
Informed Consent
Sample Size
Wound Healing
Bone and Bones

Keywords

  • β-tricalcium phosphate
  • bone
  • bone substitutes
  • histology
  • human
  • intra-bony
  • periodontal regeneration
  • recombinant human growth/differentiation factor-5
  • surgical debridement
  • tissue engineering

ASJC Scopus subject areas

  • Periodontics

Cite this

A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration. / Stavropoulos, Andreas; Windisch, Peter; Gera, Istvan; Capsius, Björn; Sculean, Anton; Wikesjö, Ulf M E.

In: Journal of Clinical Periodontology, Vol. 38, No. 11, 01.11.2011, p. 1044-1054.

Research output: Contribution to journalArticle

Stavropoulos, Andreas ; Windisch, Peter ; Gera, Istvan ; Capsius, Björn ; Sculean, Anton ; Wikesjö, Ulf M E. / A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration. In: Journal of Clinical Periodontology. 2011 ; Vol. 38, No. 11. pp. 1044-1054.
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abstract = "Aim The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier rhGDF-5/β-TCP into periodontal defects in man. Material & Methods Twenty chronic periodontitis patients, each with at least one tooth scheduled for extraction exhibiting a probing depth ≥6 mm and an associated intra-bony defect ≥4 mm participated in the study upon written informed consent. Subjects (one defect/patient) were randomized to receive open flap debridement (OFD) + rhGDF-5/β-TCP (n = 10) or OFD alone (control; n = 10). Block biopsies of the defect sites were collected at 6 months post-surgery and prepared for the histological evaluation. Two masked examiners evaluated the deepest aspect of each defect site relative to bone (height/area), periodontal ligament (PDL) and cementum regeneration, and residual β-TCP. Results Sites receiving rhGDF-5/β-TCP showed numerically greater PD reduction (3.7 ± 1.2 versus 3.1 ± 1.8 mm; p = 0.26), less gingival recession (0.5 ± 0.8 versus 1.4 ± 1.0 mm; p < 0.05) and greater clinical attachment level (CAL) gain (3.2 ± 1.7 versus 1.7 ± 2.2 mm; p = 0.14) at the deepest aspect of the defect compared with OFD alone. One biopsy in the rhGDF-5/β-TCP and four biopsies in the OFD group were deemed as not evaluable. Histologically, bone regeneration height was almost threefold greater for the rhGDF-5/β-TCP treatment compared with OFD alone (2.19 ± 1.59 versus 0.81 ± 1.02 mm; p = 0.08). Similarly an almost twofold increase was observed for PDL (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26), cementum (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26) and bone regeneration area (0.74 ± 0.69 versus 0.32 ± 0.47 mm 2; p = 0.14). Root resorption/ankylosis was not observed. Residual β-TCP occupied 8.4 ± 11.5{\%} of the area of interest in biopsies of patients receiving rhGDF-5/β-TCP. Five biopsies (one rhGDF-5/β-TCP, four OFD) were deemed unsuitable to allow a meaningful histological or histometrical evaluation. Conclusions Descriptive statistics showed greater PD reduction and CAL gain, and greater alveolar bone regeneration and periodontal regeneration at sites that received rhGDF-5/β-TCP compared to control. However, these differences were not statistically significant. Future studies with larger sample sizes will have to be conducted to verify these findings.",
keywords = "β-tricalcium phosphate, bone, bone substitutes, histology, human, intra-bony, periodontal regeneration, recombinant human growth/differentiation factor-5, surgical debridement, tissue engineering",
author = "Andreas Stavropoulos and Peter Windisch and Istvan Gera and Bj{\"o}rn Capsius and Anton Sculean and Wikesj{\"o}, {Ulf M E}",
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T1 - A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration

AU - Stavropoulos, Andreas

AU - Windisch, Peter

AU - Gera, Istvan

AU - Capsius, Björn

AU - Sculean, Anton

AU - Wikesjö, Ulf M E

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Aim The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier rhGDF-5/β-TCP into periodontal defects in man. Material & Methods Twenty chronic periodontitis patients, each with at least one tooth scheduled for extraction exhibiting a probing depth ≥6 mm and an associated intra-bony defect ≥4 mm participated in the study upon written informed consent. Subjects (one defect/patient) were randomized to receive open flap debridement (OFD) + rhGDF-5/β-TCP (n = 10) or OFD alone (control; n = 10). Block biopsies of the defect sites were collected at 6 months post-surgery and prepared for the histological evaluation. Two masked examiners evaluated the deepest aspect of each defect site relative to bone (height/area), periodontal ligament (PDL) and cementum regeneration, and residual β-TCP. Results Sites receiving rhGDF-5/β-TCP showed numerically greater PD reduction (3.7 ± 1.2 versus 3.1 ± 1.8 mm; p = 0.26), less gingival recession (0.5 ± 0.8 versus 1.4 ± 1.0 mm; p < 0.05) and greater clinical attachment level (CAL) gain (3.2 ± 1.7 versus 1.7 ± 2.2 mm; p = 0.14) at the deepest aspect of the defect compared with OFD alone. One biopsy in the rhGDF-5/β-TCP and four biopsies in the OFD group were deemed as not evaluable. Histologically, bone regeneration height was almost threefold greater for the rhGDF-5/β-TCP treatment compared with OFD alone (2.19 ± 1.59 versus 0.81 ± 1.02 mm; p = 0.08). Similarly an almost twofold increase was observed for PDL (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26), cementum (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26) and bone regeneration area (0.74 ± 0.69 versus 0.32 ± 0.47 mm 2; p = 0.14). Root resorption/ankylosis was not observed. Residual β-TCP occupied 8.4 ± 11.5% of the area of interest in biopsies of patients receiving rhGDF-5/β-TCP. Five biopsies (one rhGDF-5/β-TCP, four OFD) were deemed unsuitable to allow a meaningful histological or histometrical evaluation. Conclusions Descriptive statistics showed greater PD reduction and CAL gain, and greater alveolar bone regeneration and periodontal regeneration at sites that received rhGDF-5/β-TCP compared to control. However, these differences were not statistically significant. Future studies with larger sample sizes will have to be conducted to verify these findings.

AB - Aim The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier rhGDF-5/β-TCP into periodontal defects in man. Material & Methods Twenty chronic periodontitis patients, each with at least one tooth scheduled for extraction exhibiting a probing depth ≥6 mm and an associated intra-bony defect ≥4 mm participated in the study upon written informed consent. Subjects (one defect/patient) were randomized to receive open flap debridement (OFD) + rhGDF-5/β-TCP (n = 10) or OFD alone (control; n = 10). Block biopsies of the defect sites were collected at 6 months post-surgery and prepared for the histological evaluation. Two masked examiners evaluated the deepest aspect of each defect site relative to bone (height/area), periodontal ligament (PDL) and cementum regeneration, and residual β-TCP. Results Sites receiving rhGDF-5/β-TCP showed numerically greater PD reduction (3.7 ± 1.2 versus 3.1 ± 1.8 mm; p = 0.26), less gingival recession (0.5 ± 0.8 versus 1.4 ± 1.0 mm; p < 0.05) and greater clinical attachment level (CAL) gain (3.2 ± 1.7 versus 1.7 ± 2.2 mm; p = 0.14) at the deepest aspect of the defect compared with OFD alone. One biopsy in the rhGDF-5/β-TCP and four biopsies in the OFD group were deemed as not evaluable. Histologically, bone regeneration height was almost threefold greater for the rhGDF-5/β-TCP treatment compared with OFD alone (2.19 ± 1.59 versus 0.81 ± 1.02 mm; p = 0.08). Similarly an almost twofold increase was observed for PDL (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26), cementum (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26) and bone regeneration area (0.74 ± 0.69 versus 0.32 ± 0.47 mm 2; p = 0.14). Root resorption/ankylosis was not observed. Residual β-TCP occupied 8.4 ± 11.5% of the area of interest in biopsies of patients receiving rhGDF-5/β-TCP. Five biopsies (one rhGDF-5/β-TCP, four OFD) were deemed unsuitable to allow a meaningful histological or histometrical evaluation. Conclusions Descriptive statistics showed greater PD reduction and CAL gain, and greater alveolar bone regeneration and periodontal regeneration at sites that received rhGDF-5/β-TCP compared to control. However, these differences were not statistically significant. Future studies with larger sample sizes will have to be conducted to verify these findings.

KW - β-tricalcium phosphate

KW - bone

KW - bone substitutes

KW - histology

KW - human

KW - intra-bony

KW - periodontal regeneration

KW - recombinant human growth/differentiation factor-5

KW - surgical debridement

KW - tissue engineering

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