Elution of High Dose Amphotericin B Deoxycholate From Polymethylmethacrylate.

Fungal periprosthetic joint infections are rare, devastating complications of arthroplasty. There is conflicting evidence as to the efficacy of amphotericin B elution from cement spacers. The purpose of this study was to determine whether concentrations of amphotericin B released from bone cement over time would be efficacious in treating a periprosthetic infection. A continuous flow chamber was used to evaluate the in vitro release of amphotericin from cement beads containing 7.5% amphotericin. Following polymerization, 3.3% of the initially loaded amphotericin B was detected. The peak mean concentration eluted from the bone cement was 0.33 µg/mL at 8 hours. The AUC0-24 was 2.79 µg/mL/h; 0.20% of the amphotericin B was released. In conclusion, amphotericin B is released from bone cement at a clinically useful concentration.

Strontium-loaded mineral bone cements as sustained release systems: Compositions, release properties, and effects on human osteoprogenitor cells.

This study aims to evaluate in vitro the release properties and biological behavior of original compositions of strontium (Sr)-loaded bone mineral cements. Strontium was introduced into vaterite CaCO3 -dicalcium phosphate dihydrate cement via two routes: as SrCO3 in the solid phase (SrS cements), and as SrCl2 dissolved in the liquid phase (SrL cements), leading to different cement compositions after setting. Complementary analytical techniques implemented to thoroughly investigate the release/dissolution mechanism of Sr-loaded cements at pH 7.4 and 37°C during 3 weeks revealed a sustained release of Sr and a centripetal dissolution of the more soluble phase (vaterite) limited by a diffusion process. In all cases, the initial burst of the Ca and Sr release (highest for the SrL cements) that occurred over 48 h did not have a significant effect on the expression of bone markers (alkaline phosphatase, osteocalcin), the levels of which remained overexpressed after 15 days of culture with human osteoprogenitor (HOP) cells. At the same time, proliferation of HOP cells was significantly higher on SrS cements. Interestingly, this study shows that we can optimize the sustained release of Sr(2+) , the cement biodegradation and biological activity by controlling the route of introduction of strontium in the cement paste.

The kinetic and biological activity of different loaded rhBMP-2 calcium phosphate cement implants in rats.

The healing of large bone defects can be improved by osteogenic bone graft substitutes, due to growth factor inclusion. A sustained release of these growth factors provides more efficient bioactivity when compared with burst release and might reduce the dose required for bone regeneration, which is desirable for socioeconomical and safety reasons. In this study, we compared different rhBMP-2 loadings in a sustained release system of CaP cement and PLGA-microparticles and were able to couple kinetic to biological activity data. Fifty-two rats received a critical-size cranial defect, which was left open or filled with the cement composites. The implants consisted of plain, high, and five-fold lower dose rhBMP-2 groups. Implantation time was 4 and 12 weeks. Longitudinal in vivo release was monitored by scintigraphic imaging of (131)I-labeled rhBMP-2. Quantitative analysis of the scintigraphic images revealed a sustained release of (131)I-rhBMP-2 for both doses, with different release profiles between the two loadings. However, around 70% of the initial dose was retained in both implant formulations. Although low amounts of rhBMP-2 were released (2.4 +/- 0.8 mug in 5 weeks), histology showed defect bridging in the high-dose implants. Release out of the low-dose implants was not sufficient to enhance bone formation. Implant degradation was limited in all formulations, but was mainly seen in the high-dose group. Low amounts of sustained released rhBMP-2 were sufficient to bridge critically sized defects. A substantial amount of rhBMP-2 was retained in the implants because of the slow release rate and the limited degradation.

A rat osteoporotic spine model for the evaluation of bioresorbable bone cements.

BACKGROUND CONTEXT: As the aging population increases, the rising prevalence of osteoporosis-related spine fractures will have a dramatic impact on health care. At present, mainstay treatment relies on systemic medications intended to prevent diminishing bone mineral density (BMD) and bone mass. However, an adjunctive treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures. We term this strategy the "local treatment of osteoporosis" or osteoplasty. Potential use of osteoplasty involves the percutaneous injection of bioresorbable and bioactive bone cements into bones at risk of sustaining osteoporotic fractures. Calcium sulfate (CaSO(4)) is among the candidate bioresorbable bone cements with the material attributes desirable for potential application with osteoplasty, yet previous studies on the osteoconductive properties of CaSO(4) have been limited to animal models exhibiting normal bone biology and architecture. However, osteoporotic bone physiology may potentially interfere with the material properties of common osteoconductive biomaterials, such as that of CaSO(4). To further test this hypothesis, a suitable animal model is needed to evaluate the in vivo behavior of potential biomaterials in osteoporotic bone. PURPOSE: The purpose of this study is to evaluate the caudal (proximal tail) rat vertebral body as an appropriate system for the in vivo evaluation of bone cement performance in the osteoporotic spine. STUDY DESIGN: (1) Micro-computed tomography radiomorphometry study and (2) biomechanical vertebral compression analysis. METHODS: Female Sprague Dawley rats were ovarectomized (OVX) at age 8 weeks and subsequently maintained on a low-calcium diet for 3 months. Normal nonovarectomized female rats (NL) of similar age and size were maintained on regular rodent feed. Micro-CT analysis was performed on both the lumbar and caudal vertebrae (levels 5-7) of both groups. The following bone radiomorphometric parameters were determined: bone mineral density (BMD), average cortical thickness (ACT), average trabecular thickness (TbTh), and average trabecular spacing (TbSp). Strength and stiffness of both NL and OVX vertebral bodies were assessed under axial compression at 0.1 mm/s, whereas displacement (mm) and force (N) were measured at 10 Hz until completion to failure. After the implantation of an injectable form of CaSO(4) bone cement into caudal vertebrae, radiomorphometric analysis of cement volume, based on its unique CT absorption profile, was performed over the 8-week time period, as well as the subsequent bone response of both NL and OVX caudal vertebrae to CaSO4. RESULTS: OVX caudal vertebrae showed an 18% decrease in BMD, a 28% decrease in diaphyseal ACT, a 55% decrease in TbTh, and a 2.4-fold increase in TbSp compared with NL (p<.05). Additionally, lumbar vertebrae exhibited a 21% decrease in BMD, a 24% decrease in anterior body ACT, a 48% decrease in TbTh, and a 4.7-fold increase in TbSp (p<.05). Failure testing of OVX caudal vertebral bodies revealed a 29% decrease in strength and a 60% decrease in stiffness compared with NL (p<.01). After implantation into OVX caudal vertebrae, CaSO(4) cement exhibited a 50% decrease in initial cement volume at 2 weeks and complete resorption by 4 weeks, whereas CaSO(4) injected into NL vertebrae exhibited a 79% decrease in initial cement volume at 4 weeks, trace amounts at 6 weeks, and complete resorption by 8 weeks. At 8 weeks, NL vertebrae implanted with CaSO(4) cement exhibited increased cortical bone thickness compared with NL sham vertebrae. This CaSO(4) cement-mediated bone augmentation was altered in osteoporotic vertebrae that exhibited porous irregular cortical bone not noted in cement-treated NL vertebrae or OVX sham vertebrae. CONCLUSIONS: Future investigation of potential biomaterials intended for the local treatment of osteoporosis will require their study within an appropriate osteoporosis animal model. The OVX rat caudal spine exhibits pathologic bone changes consistent with the osteoporosis phenotype, including decreased BMD, diminished trabecular network density, cortical thinning, and decreased mechanical strength. These derangements in bone microarchitecture and physiology may contribute toward the accelerated cement resorption and altered bone response to CaSO4 observed in this study. Important advantages of the OVX rat caudal spine are the rapid and minimally invasive surgical exposure of the vertebral body and the ease of cement injection. We propose that the OVX rat caudal spine represents a valuable and cost-effective tool in the armamentarium of investigators evaluating biomaterials designed for implantation into the osteoporotic spine.