Farah Daou

Regeneration of bone tissue is tightly regulated by its complex mechanical microenvironment, in which intraosseous hydrostatic pressure (HP) and interstitial fluid flow‐induced shear stress (FSS) represent key mechanical cues. While the individual effects of these stimuli have been extensively investigated, their combined influence within physiologically relevant three‐dimensional (3D) bone tissue models remains largely unexplored due to the lack of suitable experimental platforms. In this study, we present an automated, parallelized multi‐stimuli bioreactor designed to deliver tunable combinations of FSS and intermittent HP to 3D bone tissue models. The platform integrates a direct perfusion bioreactor with a custom‐designed, modular intermittent HP unit based on a solenoid pinch valve, enabling independent and combined control of flow rate and pressure waveforms. Bioreactor performance was characterized using two biomimetic polylactic acid (PLA) scaffold types, demonstrating the ability of the system to reproduce physiologically relevant ranges of HP (1.81–30.59 kPa) and FSS (0.48–683.26 mPa). Biological experiments using bone marrow‐derived mesenchymal stem cells (BM‐MSCs) suspended in a collagen matrix and seeded into PLA scaffolds, cultured for 7 days, showed that dynamic culture conditions significantly enhanced cell viability compared with static culture. Moreover, the combination of FSS and intermittent HP stimulation within daily activity‐related ranges accelerated early osteogenic differentiation compared to direct perfusion alone. Overall, the proposed platform provides a versatile and robust investigation tool for advancing bone mechanobiology and tissue engineering research.

Advanced in vitro platforms replicating the native bone microenvironment are essential for optimizing regenerative therapies. In this study, we introduced two bone tissue-like models composed of human bone marrow-derived mesenchymal stem cells seeded onto two types of 3D-printed polylactic acid scaffolds, designed to mimic the morphological features of the trabecular bone of the iliac crest (PLA600) and those of the ulna, tibia, and femur (P3S3). To replicate the physiological environment, the bone tissue-like models were cultured within an automated multi-physical stimuli bioreactor that combines tunable fluid flow-induced shear stress, intermittent hydrostatic pressure, and pulsed electromagnetic field stimulation. We investigated how scaffold geometry influences bone marrow-derived mesenchymal stem cells mechanosensing and physical cue processing under intermittent hydrostatic pressure (15 kPa peak, 2 h/day), pulsed electromagnetic field stimulation (75 Hz, 1.5 mT, 4 h/day), and their sequential combination for 10 days. Bone marrow-derived mesenchymal stem cells exhibited a geometry-dependent sensitivity to the single stimuli, where cells within the P3S3 scaffolds were predominantly responsive to intermittent hydrostatic pressure, whereas those in the PLA600 scaffolds were highly sensitive to pulsed electromagnetic field stimulation. Notably, the geometry-dependent response gaps were mitigated by the sequential combination of intermittent hydrostatic pressure and pulsed electromagnetic field stimulation. We hypothesize that piezoelectricity and inductive coupling drive this synergy, initiating early osteogenesis via different, yet complementary molecular pathways. These findings establish a mechanistic rationale for designing personalized biophysical therapies tailored to specific bone microenvironments and anatomical sites.

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol–gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial–dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.

Background: The fracture of the calcaneus is the most common traumatic lesion of the hindfoot and can cause severe disability with social and economic sequelae. Since 1980, an increasing number of studies and new technologies have led to an improvement in the management of calcaneal fractures, but treatment is still controversial. The purpose of this review was to investigate the secondary scientific literature to detect the optimal management of calcaneal fracture. Methods: A MEDLINE search via PubMed was conducted. A total of 4856 articles were identified, and only meta-analyses and systematic reviews were included. Results: 59 articles with more than 10,000 calcaneus fractures were examined, and the results were divided into various topics. Most articles agree on the superiority of surgical treatments compared to conservative ones. Moreover, minimally invasive access to the sinus tarsi showed better results and fewer complications than traditional extended lateral access. Also, reduction and osteosynthesis with percutaneous and/or minimally invasive techniques seem to provide better outcomes when compared to open treatments. Conclusions: The management of calcaneal fractures requires an individualized treatment plan based on the functional demands of the patient, the type of fracture, and associated injuries. New technologies and further studies can lead to an improvement in the management of calcaneal fractures.

Background: Calcaneal fractures are the most frequent traumatic injuries of the hindfoot and can cause severe disability with social and economic sequelae; since 1980 an increasing number of studies and new technologies have led to an improvement in their management and complications but treatment is still controversial. The purpose of the study to review the secondary scientific literature looking for the optimal management of calcaneal fracture; Methods: through the PubMed MEDLINE database, 4856 articles were identified; only meta-analyses and systematic reviews were included in the study. Results: 59 reviews with more than 10,000 calcaneus fractures were examined and results were divided into various topics; the majority of articles agree on the superiority of surgical versus conservative treatment; minimally invasive access to the sinus tarsi shows better results and fewer complications than traditional extended lateral access; reduction and osteosynthesis with percutaneous and/or minimally invasive techniques seem to provide better outcomes if compared to open treatments. Conclusions: The management of calcaneus fractures requires an individualized planning based on the functional demands of the patient, the type of fracture and associated injuries. New technologies and further studies may still improve the management of these lesions.

Functional ability is the basis of healthy aging. Articular cartilage degeneration is amongst the most prevalent degenerative conditions that cause adverse impacts on the quality of life; moreover, it represents a key predisposing factor to osteoarthritis (OA). Both the poor capacity of articular cartilage for self-repair and the unsatisfactory outcomes of available clinical interventions make innovative tissue engineering a promising therapeutic strategy for articular cartilage repair. Significant progress was made in this field; however, a marked heterogeneity in the applied biomaterials, biofabrication, and assessments is nowadays evident by the huge number of research studies published to date. Accordingly, this literature review assimilates the most recent advances in cell-based and cell-free tissue engineering of articular cartilage and also focuses on the assessments performed via various in vitro studies, ex vivo models, preclinical in vivo animal models, and clinical studies in order to provide a broad overview of the latest findings and clinical translation in the context of degenerated articular cartilage and OA.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posed a serious public health concern and started a race against time for researchers to discover an effective and safe therapy for coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2. This review aims to describe the history, efficacy, and safety of five potential therapeutics for COVID-19, remdesivir, favipiravir, hydroxychloroquine, tocilizumab, and convalescent plasma. A literature review was conducted through October 2020 to identify published studies evaluating the efficacy and safety of these five potential therapeutics. Clinical improvement was used to assess the efficacy, while reported withdrawals from study participation and adverse events were used to evaluate the safety. In total, 95 clinical studies (6 interventional and 89 observational studies) were obtained, of which 42 were included in this review. The evaluation of the efficacy and safety profiles is challenging due to the limitations of the clinical studies on one hand, and the limited number of randomized controlled trials (RCTs) on the other. Moreover, there was insufficient evidence to support repurposing remdesivir, favipiravir, and tocilizumab for COVID-19.

Aflatoxin B1 (AFB1) is the most potent of the dietary aflatoxins, and its major metabolite, aflatoxin M1 (AFM1), is frequently found in the breast milk of lactating mothers. The aim of this study was to assess the occurrence and factors associated with AFM1 contamination of breast milk collected from lactating mothers in Lebanon. A total of 111 breast milk samples were collected according to the guidelines set by the World Health Organization. Samples were analyzed with a competitive enzyme-linked immunosorbent assay between December 2015 and November 2016. A survey was used to determine the demographic and anthropometric characteristics of participating lactating mothers. Dietary habits were assessed using a semiquantitative food frequency questionnaire. Mean (±standard deviation) concentration of AFM1 in the breast milk samples was 4.31 ± 1.8 ng/L, and 93.8% of samples contained AFM1 at 0.2 to 7.9 ng/L. The mean concentration of AFM1 was significantly lower (P < 0.05) in fall and winter (4.1 ± ...