ABSTRACT
OBJECTIVE: The rise in primary and revision surgeries utilizing joint replacement implants suggest the need for more reliable means of promoting implant fixation. Zoledronate-(Zol), cytochalasin-D-(cytoD), and desferrioxamine-(DFO) have been shown to enhance mesenchymal stem cell (MSC) differentiation into osteoblasts promoting bone formation. The objective was to determine whether Zol, cytoD, and DFO can improve fixation strength and enhance peri-implant bone volume about intra-medullary femoral implants. METHODS: 48 Sprague-Dawley female rats were randomized into four treatments, saline-control or experimental: Zol-(0.8 µg/µL), cytoD-(0.05 µg/µL), DFO-(0.4 µg/µL). Implants were placed bilaterally in the femoral canals following injection of treatment solution and followed for 28 days. Mechanical push-out testing and micro-CT were our primary evaluations, measuring load to failure and bone volume. Qualitative evaluation included histological assessment. Data was analyzed with a one-way ANOVA with Holm-Sidak mean comparison testing. RESULTS: Significant results included pushout tests showing an increase in maximum energy for Zol (124%) and cytoD (82%); Zol showed an increase in maximum load by 48%; Zol micro-CT showed increase in BV/TV by 35%. CONCLUSIONS: Our findings suggest that locally applied Zol and cytoD enhance implant mechanical stability. Bisphosphonates and actin regulators, like cytoD, might be further investigated as a new strategy for improving osseointegration.
Subject(s)
Bone Density Conservation Agents/pharmacology , Bone-Anchored Prosthesis , Cytochalasin D/pharmacology , Deferoxamine/pharmacology , Femur/diagnostic imaging , Zoledronic Acid/pharmacology , Animals , Drug Evaluation, Preclinical/methods , Female , Femur/drug effects , Femur/surgery , Models, Animal , Nucleic Acid Synthesis Inhibitors/pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley , Siderophores/pharmacologyABSTRACT
BACKGROUND: Results of previous studies have shown that piroxicam, a cyclooxygenase-1-2 inhibitor, improves the strength of healing ligaments, whereas celecoxib, a cyclooxygenase-2 inhibitor, impairs ligament healing. HYPOTHESIS: The selective cyclooxygenase-1 inhibitor, SC-560, will improve the strength of ligament healing in an in vivo rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Eighty male Sprague-Dawley rats underwent surgical transection of their medial collateral ligament. Postoperatively, 20 rats were given SC-560 at a low dose and 20 at a high dose for the first 6 days of recovery; the other 40 received a normal diet. The animals were sacrificed 14 days later, and both the injured and uninjured ligaments were mechanically tested to failure in tension. RESULTS: No significant differences in the strength of injured ligaments were found between drug and placebo treatment. However, the contralateral uninjured ligaments in the SC-560-treated groups failed at 27% higher energy and 22% higher load. CONCLUSIONS: This cyclooxygenase-1 inhibitor did not improve the strength of ligament healing but did significantly improve the strength of the contralateral uninjured ligament. CLINICAL RELEVANCE: A pure cyclooxygenase-1 inhibitor is probably not indicated as a positive influence on ligament healing but might provide benefits in ligament injury prevention.