RESUMEN
Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed "micropetrosis". Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of â¼80 nm to â¼3 µm wide, distinctly faceted, magnesium whitlockite [Ca18Mg2(HPO4)2(PO4)12] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.
Asunto(s)
Proceso Alveolar/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Fosfatos de Calcio/química , Difosfonatos/farmacología , Magnesio/química , Osteocitos/efectos de los fármacos , Proceso Alveolar/química , Proceso Alveolar/citología , Proceso Alveolar/patología , Apoptosis/efectos de los fármacos , Conservadores de la Densidad Ósea/uso terapéutico , Cristalización , Difosfonatos/uso terapéutico , Femenino , Humanos , Osteocitos/química , Osteocitos/citología , Osteocitos/patología , Fracturas Osteoporóticas/tratamiento farmacológico , Fracturas Osteoporóticas/patologíaRESUMEN
The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal morphologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact) and also in extracts i.e. media modified by the material (indirect contact). Additionally, the effect of supplementing the extracts with calcium ions and/or proteins was investigated. Macrophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate's microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate-like crystals substrates compared to the almost non-existent release on needle-like substrates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials.
Asunto(s)
Durapatita/efectos adversos , Durapatita/química , Inflamación/etiología , Nanoestructuras , Animales , Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/química , Línea Celular , Proliferación Celular , Células Cultivadas , Inflamación/metabolismo , Activación de Macrófagos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Nanoestructuras/química , Nanoestructuras/ultraestructura , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Some of the current clinical and biomechanical data suggest that vertebroplasty causes the development of adjacent vertebral fractures shortly after augmentation. These findings have been attributed to high injection volumes as well as high Young's moduli of PMMA bone cements compared to that of the osteoporotic cancellous bone. The aim of this study was to evaluate the use of castor oil as a plasticizer for PMMA bone cements. The Young's modulus, yield strength, maximum polymerization temperature, doughing time, setting time and the complex viscosity curves during curing, were determined. The cytotoxicity of the materials extracts was assessed on cells of an osteoblast-like cell line. The addition of up to 12 wt% castor oil decreased yield strength from 88 to 15 MPa, Young's modulus from 1500 to 446 MPa and maximum polymerization temperature from 41.3 to 25.6°C, without affecting the setting time. However, castor oil seemed to interfere with the polymerization reaction, giving a negative effect on cell viability in a worst-case scenario.