Mimicking bone microenvironment: 2D and 3D in vitro models of human osteoblasts.

Understanding the in vitro biology and behavior of human osteoblasts is crucial for developing research models that reproduce closely the bone structure, its functions, and the cell-cell and cell-matrix interactions that occurs in vivo. Mimicking bone microenvironment is challenging, but necessary, to ensure the clinical translation of novel medicines to treat more reliable different bone pathologies. Currently, bone tissue engineering is moving from 2D cell culture models such as traditional culture, sandwich culture, micro-patterning, and altered substrate stiffness, towards more complex 3D models including spheroids, scaffolds, cell sheets, hydrogels, bioreactors, and microfluidics chips. There are many different factors, such cell line type, cell culture media, substrate roughness and stiffness that need consideration when developing in vitro models as they affect significantly the microenvironment and hence, the final outcome of the in vitro assay. Advanced technologies, such as 3D bioprinting and microfluidics, have allowed the development of more complex structures, bridging the gap between in vitro and in vivo models. In this review, past and current 2D and 3D in vitro models for human osteoblasts will be described in detail, highlighting the culture conditions and outcomes achieved, as well as the challenges and limitations of each model, offering a widen perspective on how these models can closely mimic the bone microenvironment and for which applications have shown more successful results.

Trough to peak ratio of once-daily lisinopril and twice-daily captopril in patients with essential hypertension.

The objective of this study was to assess the antihypertensive effect and the trough to peak (T:P) ratio of lisinopril and captopril, in patients with essential hypertension. After 2 weeks of placebo, 69 of 115 eligible patients had office diastolic blood pressure (DBP) between 90 and 114 mm Hg and daytime average DBP above 85 mm Hg during a 25-h ambulatory BP monitoring (ABPM) and were randomised to receive lisinopril (20 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Office and ambulatory BP were then repeated. Indices of 24-h BP and T:P ratios were calculated and compared. Both drugs significantly reduced both office and ambulatory BP. The final BP obtained with lisinopril was less than with captopril. On office measurement, 75% of the patients treated with lisinopril and 44% on captopril were controlled (P < 0.001), but responses by ABPM were not significantly different. T:P ratios calculated in all patients were 0.75 and 0.66 for lisinopril and captopril respectively, but in patients who responded to each drug the corresponding ratios were 0.78 and 0.73. In conclusion both 20 mg once-daily lisinopril and 50 mg captopril twice-daily achieve a favourable T:P ratio in patients with essential hypertension.