title: Closure of rabbit calvarial critical-sized defects using protective composite allogeneic and alloplastic bone substitutes.
abstract: This study evaluated the repair of critical-sized cranial vault defects in thirty New Zealand white rabbits using various allogeneic and alloplastic bone substitutes designed to provide mechanical protection to the brain as well as osteoinductivity. The strategies employed included demineralized bone matrix (DBM), a putty used in combination with a rigid resorbable plating system as a protective covering and calcium phosphate cement (CPC) combined with native partially purified bone morphogenetic protein (BMP). Bilateral critical-sized defects measuring 15 mm in diameter were created in the parietal bones of 30 adult male New Zealand white rabbits. They were divided into three groups with ten animals in each. Group 1 had one defect left unfilled as a control while autogenous bone was placed in the defect on the other side. In Group 2 a rigid resorbable copolymer membrane, Lactosorb (Lorenz Surgical, Jacksonville, Florida), was placed over both defects to cover them and protect the underlying tissues. The pericranial aspect of one defect was left unfilled while the other defect was filled with DBM putty. Group 3 had a CPC, Mimix (Lorenz Surgical, Jacksonville, Florida), placed into one of the defects while the defect on the other side was filled with the same CPC in combination with BMP in a concentration of 25 mg/mL. Bone healing was assessed clinically, radiographically, and histomorphometrically. All unfilled controlled defects, the defects covered with the resorbable Lactosorb membrane and those filled with calcium phosphate cement alone, healed with a fibrous scar. Defects reconstructed with DBM putty in combination with the resorbable Lactosorb membrane and calcium phosphate in combination with BMP healed with bone bridging the entire defect. This was obvious radiographically where the defects appeared completely filled with a dense radiopaque tissue. Histological analysis demonstrated that specimens where DBM putty was used in combination with the resorbable Lactosorb membrane had 67.7% new bone fill at 6 weeks and 84.0% at 12 weeks. Resorption of DBM particles was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. In the calcium phosphate groups where BMP was added to the bioimplant there was 45.8% new bone formation at 12 weeks. The utilization of a composite consisting of DBM with resorbable Lactosorb membrane or a composite of calcium phosphate cement composite with BMP promoted complete closure of critical-sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks. The complete bone bridging observed with these composites suggests that they could be used to enhance the protection of intracranial contents following craniofacial surgical procedures.
authors.affiliation: Orthobiologics Laboratory and Oral and Maxillofacial Surgery, University of Toronto, Toronto, Ontario, Canada. george.sandor@utoronto.ca
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Haddad
authors.forename: Sean A F
authors.initials: SA
authors.lastname: Peel
authors.forename: Cameron M L
authors.initials: CM
authors.lastname: Clokie
authors.forename: George K B
authors.initials: GK
authors.lastname: Sándor
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D018786:Bone Substitutes / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000627:therapeutic use; D019344:Lactic Acid / Q000627:therapeutic use; D008297:Male; D011100:Polyglycolic Acid / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000627:therapeutic use; D011817:Rabbits; D011859:Radiography; D012886:Skull / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000293:injuries / Q000601:surgery*
chemical_list: D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C020243:calcium phosphate