Bone is a regenerative organ characterized by self-renewal ability. Indeed, it is a very dynamic tissue subjected to continuous remodeling in order to preserve its structure and function. However, in clinical practice, impaired bone healing can be observed in patients and medical intervention is needed to regenerate the tissue via the use of natural bone grafts or synthetic bone grafts. The main elements required for tissue engineering include cells, growth factors and a scaffold material to support them. Three different materials (metals, ceramics, and polymers) can be used to create a scaffold suitable for bone regeneration. Several cell types have been investigated in combination with biomaterials. In this review, we describe the options available for bone regeneration, focusing on tissue engineering strategies based on the use of different biomaterials combined with cells and growth factors.

We report a new sensitive label-free electrochemical immunosensor to detect Vitamin D₃ (25-OHD₃) in untreated serum samples. To this aim, a graphite screen printed electrode (SPE) was modified using cysteamine (CYM) functionalized core-shell magnetic nanoparticles (Au@MNPs) then, the 25-OHD₃ antibody (AbD) was immobilized via glutaraldehyde crosslinking. The several steps involved in the immunosensor development and 25-OHD₃ analysis were monitored by using differential pulse voltammetry (DPV). The developed immunosensor showed a LOD of 2.4 ng mL^-1 and a linear range between 7.4 and 70 ng mL^-1. The effectiveness of the immunosensor in human serum analysis was assessed by comparing the results obtained with the chemiluminescence-immunoassay (CLIA) reference method. The high sensitivity and excellent agreement with the reference method suggest its potential use as a POCT to monitor hypovitaminosis 25-OHD levels.

Background. We sought to investigate the mutual interplay between bone, glucose and lipid metabolism in a wide cohort of community-based subjects. Methods. We studied 1240 blood donors (F/M ratio 1/3.2, mean age 41.9 ± 11.7 SD). Serum ionized (Ca⁺⁺), magnesium (Mg⁺⁺), 25-hydroxy-vitamin D [25(OH)D], PTH-1-84, 1,25-dihydroxyvitamin D [1,25(OH)₂D], total cholesterol (C), HDL-C, triglycerides and glucose were measured and LDL-C levels were calculated in all subjects. Results. 25(OH)D negatively correlated with BMI (R = −0.11), PTH (R = −0.16) (p < 0.0001), total C (R = −0.06, p < 0.05) and triglycerides (R = −0.13, p < 0.0001) and positively with 1,25(OH)₂D (R = 0.12) and creatinine (R = 0.17) (p < 0.0001). Serum PTH positively correlated with total C (R = 0.08, p < 0.01), LDL-C (R = 0.1, p < 0.001), triglycerides (R = 0.09, p < 0.01) and glucose (R = 0.15, p < 0.0001) and negatively with HDL-C (R = −0.09, p < 0.01). The odds of showing abnormal serum triglycerides and HDL-C increased as 25(OH)D decreased (p < 0.0001 and p < 0.03) and PTH increased (p < 0.03 and p = 0.05), while the odds of showing abnormal LDL-C levels increased in association with elevated PTH (p < 0.01). Conclusion. Vitamin D, PTH, glucose and lipid metabolism are mutually influenced. Hypovitaminosis D predisposes toward worsening lipid profiles through the actions of PTH, while serum PTH levels per se associate with higher glucose and LDL-C levels.

Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.

The use of a higher dose per fraction to overcome the high radioresistance of prostate cancer cells has been unsuccessfully proposed. Herein, we present PC3 and DU-145, castration-resistant prostate cancer cell lines that survived a clinically used ultra-higher dose per fraction, namely, radioresistant PC3 and DU-145 cells (PC3RR and DU-145RR). Compared to PC3, PC3RR showed a higher level of aggressive behaviour, with enhanced clonogenic potential, DNA damage repair, migration ability and cancer stem cell features. Furthermore, compared to PC3, PC3RR more efficiently survived further radiation by increasing proliferation and down-regulating pro-apoptotic proteins. No significant changes of the above parameters were described in DU-145RR, suggesting that different prostate cancer cell lines that survive ultra-higher dose per fraction do not display the same grade of aggressive phenotype. Furthermore, both PC3RR and DU-145RR increased antioxidant enzymes and mesenchymal markers. Our data suggest that different molecular mechanisms could be potential targets for future treatments plans based on sequential strategies and synergistic effects of different modalities, possibly in a patient-tailored fashion. Moreover, PC3RR cells displayed an increase in specific markers involved in bone remodeling, indicating that radiotherapy selects a PC3 population capable of migrating to secondary metastatic sites. Finally, PC3RR cells showed a better sensitivity to Docetaxel as compared to native PC3 cells. This suggests that a subset of patients with castration-resistant metastatic disease could benefit from upfront Docetaxel treatment after the failure of radiotherapy.