Bone engineering of the rabbit ulna.
OBJECTIVE
The purpose of the present preliminary study is to show that a novel 3-dimensional porous silica-calcium phosphate nanocomposite (SCPC) can provide a controlled release of rhBMP-2 and regenerate bone in a load-bearing segmental defect.


METHODS
A bone replica of the rabbit ulna was created from SCPC powder using rapid prototyping technology. The ceramic bone replica was coated with rhBMP-2 and then implanted into a 10-mm segmental defect created in a rabbit ulna and fixated with a 1-mm titanium adaptation plate. Bone healing was evaluated using computed tomography (CT) scan, histomorphometry, and biomechanical techniques. The release kinetics of rhBMP-2 and the dissolution kinetics were also determined in vitro. Statistical analysis was performed to compare the biomechanical strength of the grafted bone with the contralateral unoperated ulna.


RESULTS
After 4 weeks, CT scans showed that the critical size defect had been replaced by newly formed bone. Torsional testing of the ulna after 12 weeks showed restoration of maximum torque and angle at failure. Histological evaluation showed that the regenerated bone had the morphological characteristics of mature bone. SCPC provided a sustained release profile of an effective dose of rhBMP-2 for 14 days.


CONCLUSIONS
The SCPC-rhBMP-2 hybrid enhanced bone regeneration in a load-bearing segmental defect in a rabbit ulna. The regenerated bone acquired morphology and mechanical strength typical for natural bone. The enhanced bone formation correlates well with the surface bioactivity and effective release profile of rhBMP-2. The present preliminary study shows the proof of principles that porous, resorbable, bioactive SCPC-rhBMP-2 tissue engineering hybrid can serve as a substitute for autologous bone in load-bearing applications.
El-Ghannam
Ahmed
A
Center for Biomedical Engineering and Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY 40506, USA. arelgh2@uky.edu
Cunningham
Larry
L
Pienkowski
David
D
Hart
Amanda
A
D020341:Absorbable Implants; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D018786:Bone Substitutes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D048091:Guided Tissue Regeneration / Q000379:methods; D006801:Humans; D008297:Male; D008422:Materials Testing; D053761:Nanocomposites / Q000737:chemistry / Q000627:therapeutic use*; D016348:Osseointegration / Q000187:drug effects / Q000502:physiology; D011474:Prosthesis Design / Q000379:methods*; D011817:Rabbits; D011994:Recombinant Proteins; D017640:Silicates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023822:Tissue Engineering / Q000379:methods; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D014457:Ulna / Q000187:drug effects* / Q000601:surgery
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D017640:Silicates; D016212:Transforming Growth Factor beta; C499768:silica-calcium phosphate nanocomposite