Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2

Sheldon X. Lu, Tiago Fiorini, Jaebum Lee, Hari S. Prasad, Amanda N. Buxton, Fredrick C. Bisch, Douglas R. Dixon, Cristiano Susin, Ulf M E Wikesjö

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM). Methods Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/β-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation. Results Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm2, p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages. Conclusions rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s).

Original languageEnglish (US)
Pages (from-to)688-697
Number of pages10
JournalJournal of Clinical Periodontology
Volume40
Issue number7
DOIs
StatePublished - Jul 1 2013

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Porifera
Collagen
Osteogenesis
Seroma
Osseointegration
Bone and Bones
Ceramics
Newfoundland and Labrador
Benchmarking
Inlays
Durapatite
recombinant human bone morphogenetic protein-2
Skeleton
Bone Density
Macrophages
Observation
Dogs
Wounds and Injuries
Therapeutics

Keywords

  • biomaterials
  • bone
  • bone morphogenetic protein
  • osseointegration
  • tissue engineering

ASJC Scopus subject areas

  • Periodontics

Cite this

Lu, S. X., Fiorini, T., Lee, J., Prasad, H. S., Buxton, A. N., Bisch, F. C., ... Wikesjö, U. M. E. (2013). Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2. Journal of Clinical Periodontology, 40(7), 688-697. https://doi.org/10.1111/jcpe.12109

Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2. / Lu, Sheldon X.; Fiorini, Tiago; Lee, Jaebum; Prasad, Hari S.; Buxton, Amanda N.; Bisch, Fredrick C.; Dixon, Douglas R.; Susin, Cristiano; Wikesjö, Ulf M E.

In: Journal of Clinical Periodontology, Vol. 40, No. 7, 01.07.2013, p. 688-697.

Research output: Contribution to journalArticle

Lu, SX, Fiorini, T, Lee, J, Prasad, HS, Buxton, AN, Bisch, FC, Dixon, DR, Susin, C & Wikesjö, UME 2013, 'Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2', Journal of Clinical Periodontology, vol. 40, no. 7, pp. 688-697. https://doi.org/10.1111/jcpe.12109
Lu, Sheldon X. ; Fiorini, Tiago ; Lee, Jaebum ; Prasad, Hari S. ; Buxton, Amanda N. ; Bisch, Fredrick C. ; Dixon, Douglas R. ; Susin, Cristiano ; Wikesjö, Ulf M E. / Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2. In: Journal of Clinical Periodontology. 2013 ; Vol. 40, No. 7. pp. 688-697.
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abstract = "Background Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM). Methods Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/β-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation. Results Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm2, p = 0.03) and bone density (24.1 ± 1.4{\%} versus 14.6 ± 2.0{\%}, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100{\%} of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages. Conclusions rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s).",
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AU - Fiorini, Tiago

AU - Lee, Jaebum

AU - Prasad, Hari S.

AU - Buxton, Amanda N.

AU - Bisch, Fredrick C.

AU - Dixon, Douglas R.

AU - Susin, Cristiano

AU - Wikesjö, Ulf M E

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N2 - Background Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM). Methods Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/β-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation. Results Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm2, p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages. Conclusions rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s).

AB - Background Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM). Methods Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/β-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation. Results Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm2, p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages. Conclusions rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s).

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