Effect of recombinant human bone morphogenetic protein-2 on bone regeneration in large defects of the growing canine skull after dura mater replacement with a dura mater substitute: Laboratory investigation

Dongmei He, Davi D.G. Genecov, Morley Herbert, Raul Barcelo, Mohammed Elsayed Elsalanty, Bradley E. Weprin, Lynne A. Opperman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Object. This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a collagen sponge-collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines. Methods. Forty immature male beagles were used to create two 2.5 x 4-cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 x 3-cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15% hydroxyapatite [HA]/85% tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed. Results. Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non-rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05). Conclusions. The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalJournal of neurosurgery
Volume112
Issue number2
DOIs
StatePublished - Feb 1 2010

Fingerprint

Dura Mater
Bone Regeneration
Skull
Canidae
Collagen
Porifera
Durapatite
Bone and Bones
Osteogenesis
recombinant human bone morphogenetic protein-2
Seroma
Bone Matrix
Ceramics
Sutures

Keywords

  • Bone generation
  • Dura mater repair
  • Large cranial defect
  • Recombinant human bone morphogenetic protein-2

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Effect of recombinant human bone morphogenetic protein-2 on bone regeneration in large defects of the growing canine skull after dura mater replacement with a dura mater substitute : Laboratory investigation. / He, Dongmei; Genecov, Davi D.G.; Herbert, Morley; Barcelo, Raul; Elsalanty, Mohammed Elsayed; Weprin, Bradley E.; Opperman, Lynne A.

In: Journal of neurosurgery, Vol. 112, No. 2, 01.02.2010, p. 319-328.

Research output: Contribution to journalArticle

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title = "Effect of recombinant human bone morphogenetic protein-2 on bone regeneration in large defects of the growing canine skull after dura mater replacement with a dura mater substitute: Laboratory investigation",
abstract = "Object. This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a collagen sponge-collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines. Methods. Forty immature male beagles were used to create two 2.5 x 4-cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 x 3-cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15{\%} hydroxyapatite [HA]/85{\%} tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed. Results. Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non-rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05). Conclusions. The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.",
keywords = "Bone generation, Dura mater repair, Large cranial defect, Recombinant human bone morphogenetic protein-2",
author = "Dongmei He and Genecov, {Davi D.G.} and Morley Herbert and Raul Barcelo and Elsalanty, {Mohammed Elsayed} and Weprin, {Bradley E.} and Opperman, {Lynne A.}",
year = "2010",
month = "2",
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doi = "10.3171/2009.1.JNS08976",
language = "English (US)",
volume = "112",
pages = "319--328",
journal = "Journal of Neurosurgery",
issn = "0022-3085",
publisher = "American Association of Neurological Surgeons",
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TY - JOUR

T1 - Effect of recombinant human bone morphogenetic protein-2 on bone regeneration in large defects of the growing canine skull after dura mater replacement with a dura mater substitute

T2 - Laboratory investigation

AU - He, Dongmei

AU - Genecov, Davi D.G.

AU - Herbert, Morley

AU - Barcelo, Raul

AU - Elsalanty, Mohammed Elsayed

AU - Weprin, Bradley E.

AU - Opperman, Lynne A.

PY - 2010/2/1

Y1 - 2010/2/1

N2 - Object. This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a collagen sponge-collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines. Methods. Forty immature male beagles were used to create two 2.5 x 4-cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 x 3-cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15% hydroxyapatite [HA]/85% tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed. Results. Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non-rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05). Conclusions. The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.

AB - Object. This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a collagen sponge-collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines. Methods. Forty immature male beagles were used to create two 2.5 x 4-cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 x 3-cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15% hydroxyapatite [HA]/85% tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed. Results. Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non-rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05). Conclusions. The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.

KW - Bone generation

KW - Dura mater repair

KW - Large cranial defect

KW - Recombinant human bone morphogenetic protein-2

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