title: Evaluation of short-term healing following sustained delivery of osteoinductive agents in a rat femur drill defect model.
abstract: The bone morphogenetic proteins (BMPs) carry a crucial role in bone formation and bone healing. Previous studies have identified the osteoinductive capabilities of demineralized bone matrix (DBM) and the individual factor osteogenic protein-1 (OP-1), also known as BMP-7. The purpose of this study is to identify the short-term healing effects of targeted drug delivery of demineralized bone matrix and osteogenic protein-1 following bony trauma in terms of mechanical strength and histological changes. Animals in Group 1 acted as the control and Group 2 received a unicortical drill defect and placement of a calcined tricalcium phosphate lysine (TCPL) capsule containing antibiotic (sham). Group 3 and 4 animals had a created drill defect and received a TCPL carrier containing antibiotic along with DBM or OP-1, respectively. After 2 weeks post-implantation, animals in each group were sacrificed before the retrieval of the bone. The femurs were analyzed biomechanically for return of strength and histologically for bone growth. The average rupture strength for the femurs of the control group was shown to be significantly higher than all other groups (p<0.001 compared to sham, DBM, and OP-1). There was no significant difference between the two treatment groups (p=0.984) and there was no significant difference between the sham and DBM or OP-1 treated groups (p=0.908 and p=0.991, respectively). Analysis of the gross specimens showed minimal signs of bone regeneration at the defect site for both DBM and OP-l treated femurs when compared to the shams. Histological sections did show increased cortical thickness and new bone formation in the DBM and OP-1 groups, with the OP-1 group appearing slightly thicker. Despite the histological changes seen, the results indicate that there is no significant improvement in mechanical strength during the early stages of healing regardless of treatment.
authors.affiliation: Department of Orthopaedic Surgery and Rehabilitation, University of Mississippi Medical Center, Jackson, MS, 39216, USA. swingerter@orthopedics.umsmed.edu
authors.forename: Scott
authors.initials: S
authors.lastname: Wingerter
authors.forename: Michelle
authors.initials: M
authors.lastname: Tucci
authors.forename: Joel
authors.initials: J
authors.lastname: Bumgardner
authors.forename: Ham
authors.initials: H
authors.lastname: Benghuzzi
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D005264:Femoral Fractures / Q000188:drug therapy* / Q000473:pathology*; D005269:Femur / Q000187:drug effects / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations