Current osteoinductive protein therapy utilizes bolus administration of large doses of bone morphogenetic proteins (BMPs), which is costly, and may not replicate normal bone healing. The limited in vivo biologic activity of BMPs requires the investigation of growth factors that may enhance this activity. In this study, we utilized the C3H10T1/2 murine mesenchymal stem cell line to test the hypotheses that osteoactivin (OA) has comparable osteoinductive effects to bone morphogenetic protein-2 (BMP-2), and that sustained administration of either growth factor would result in increased osteoblastic differentiation as compared to bolus administration. Sustained release biodegradable hydrogels were designed, and C3H10T1/2 cells were grown on hydrogels loaded with BMP-2 or OA. Controls were grown on unloaded hydrogels, and positive controls were exposed to bolus growth factor administration. Cells were harvested at several time points to assess osteoblastic differentiation. Alkaline phosphatase (ALP) staining and activity, and gene expression of ALP and osteocalcin were assessed. Treatment with OA or BMP-2 resulted in comparable effects on osteoblastic marker expression. However, cells grown on hydrogels demonstrated osteoblastic differentiation that was not as robust as cells treated with bolus administration. This study shows that OA has comparable effects to BMP-2 on osteoblastic differentiation using both bolus administration and continuous release, and that bolus administration of OA has a more profound effect than administration using hydrogels for sustained release. This study will lead to a better understanding of appropriate delivery methods of osteogenic growth factors like OA for repair of fractures and segmental bone defects.
Introduction
Complex sacral fractures with vertical and anterior pelvic ring instability treated with traditional fixation methods are associated with high rates of failure and poor clinical outcomes. Supplemental lumbopelvic fixation(LPF) has been utilized for additional stability to help with fracture union. The purpose of this study was to determine if minimally invasive LPF provides reliable fracture stability and acceptable complication rates in complex sacral fractures.
Methods
Twenty-eight patients were retrospectively chosen from a pool of 105 at our level 1 trauma center (2008–2014) who had undergone LPF. Patients underwent posterior sacroiliac fixation, with or without anterior fixation, followed by minimally invasive LPF. Main outcomes were return to the operating room (OR) for instrumentation revision secondary to loss of correction or failure of fixation, return to the OR for treatment of infection, radiographic evaluation to assess for loss of reduction. ISS score, transfusion requirements, length of hospital stay, postoperative day at mobilization, and mortality were also evaluated.
Results
Three patients returned to the OR for infection (11%). One patient required revision surgery for instrumentation malposition and neurologic deficit (3.5%). No patients required return to the OR for revision due to failure of instrumentation or loss of correction. The average length of surgery was 3.9 hours and estimated blood loss was 192 mL. The average transfusion requirement was 2.2 units of packed red blood cells and the majority of patients were mobilized at postoperative day 4. There were no mortalities.
Conclusion
This is currently the largest series of high energy complex sacral fractures treated with minimally invasive LPF. The results demonstrate reliable maintenance of reduction with a low complication rate.
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