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

• Published in: Journal of clinical periodontology 2013-07, Vol.40 (7), p.688-697
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Alveolar Bone Loss - surgery; Animals; Biodegradation; biomaterials; bone; Bone Density - drug effects; Bone Density - physiology; Bone Matrix - drug effects; Bone Matrix - pathology; bone morphogenetic protein; Bone Morphogenetic Protein 2 - administration & dosage; Bone Morphogenetic Protein 2 - therapeutic use; Bone Regeneration - drug effects; Bone Regeneration - physiology; Bone Remodeling - drug effects; Bone Remodeling - physiology; Collagen Type I - chemistry; Dental Implantation, Endosseous - methods; Dentistry; Dogs; Drug Carriers; Drug Delivery Systems; Foam Cells - pathology; Humans; Hydroxyapatites - chemistry; Male; Materials Testing; Maxillofacial surgery; osseointegration; Osseointegration - drug effects; Osseointegration - physiology; Osteogenesis - drug effects; Osteogenesis - physiology; Proteins; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Seroma - etiology; Surgical outcomes; tissue engineering; Tissue Scaffolds - chemistry; Tooth Extraction; Tooth Socket - surgery; Transforming Growth Factor beta - administration & dosage; Transforming Growth Factor beta - therapeutic use; Transplants & implants
• ISSN: 0303-6979; 1600-051X
• DOI: 10.1111/jcpe.12109

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).