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Titanium and titanium alloys are the prevailing dental implant materials owing to their favorable mechanical properties and biocompatibility, but how roughness dictates the biological response is still a matter of debate. In this study, laser texturing was used to generate eight paradigmatic roughened surfaces, with the aim of studying the early biological response elicited on MC3T3-E1 pre-osteoblasts. Prior to cell tests, the samples underwent SEM analysis, optical profilometry, protein adsorption assay, and optical contact angle measurement with water and diiodomethane to determine surface free energy. While all the specimens proved to be biocompatible, supporting similar cell viability at 1, 2, and 3 days, surface roughness could impact significantly on cell adhesion. Factorial analysis and linear regression showed, in a robust and unprecedented way, that an isotropic distribution of deep and closely spaced valleys provides the best condition for cell adhesion, to which both protein adsorption and surface free energy were highly correlated. Overall, here the authors provide, for the first time, a thorough investigation of the relationship between roughness parameters and osteoblast adhesion that may be applied to design and produce new tailored interfaces for implant materials. [ABSTRACT FROM AUTHOR]

The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical–physical features of the matrix, while others may come from the 'outer' environment, as in the case of mechanical loading applied on the bones. In addition to these forces, a plethora of chemical signals drives cell physiology and fate, possibly leading to dysfunctions when the homeostasis is disrupted. This variety of stimuli triggers different responses among the tissues: bones represent a particular milieu in which a fragile balance between mechanical and metabolic demands should be tuned and maintained by the concerted activity of cell biomolecules located at the interface between external and internal environments. Plasma membrane ion channels can be viewed as multifunctional protein machines that act as rapid and selective dual-nature hubs, sensors, and transducers. Here we focus on some multisensory ion channels (belonging to Piezo, TRP, ASIC/EnaC, P2XR, Connexin, and Pannexin families) actually or potentially playing a significant role in bone adaptation to three main stressors, mechanical forces, oxidative stress, and acidosis, through their effects on bone cells including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. Ion channel-mediated bone remodeling occurs in physiological processes, aging, and human diseases such as osteoporosis, cancer, and traumatic events. [ABSTRACT FROM AUTHOR]

Background: Treatments to reduce red blood cell (RBC) transfusion burden among patients with transfusion-dependent β-thalassaemia remain limited. Here, we report long-term follow-up data from the phase 3 BELIEVE trial of luspatercept for transfusion-dependent β-thalassaemia., Methods: BELIEVE was a phase 3, randomised, double-blind, placebo-controlled study performed at 65 sites in 15 countries. The trial included adults with transfusion-dependent β-thalassaemia or haemoglobin E/β-thalassaemia and Eastern Cooperative Oncology Group score of 0-1. Patients were randomly assigned (2:1) using integrated response technology stratified by region to luspatercept (1·0-1·25 mg/kg) or placebo administered subcutaneously once every 21 days. After study unblinding, patients could receive luspatercept in the open-label extension phase (crossover allowed). The primary endpoint results (proportion of patients with reduction in transfusion burden of ≥33% and ≥2 RBC units during weeks 13-24) are described elsewhere; herein we present an update to the primary endpoint analysis consequent to late-reported transfusion events. We also report long-term efficacy (intention-to-treat population) and safety data (safety population) for patients followed up for approximately 3 years. This trial is registered on ClinicalTrials.gov (NCT02604433) and is completed., Findings: Between May 2, 2016, and May 16, 2017, 336 patients were randomly assigned to luspatercept (n=224) or placebo (n=112). The median age of patients was 30 years (IQR 23-40); 195 (58%) were female and 141 (42%) male. As of Jan 5, 2021, the median duration of treatment in the luspatercept group was 153·6 weeks (IQR 81·0-171·0) and median study follow-up was 163·1 weeks (140·5-176·2). Due to the difference in treatment duration between the luspatercept and placebo groups, no comparative analyses between the two groups were performed after week 96. Patients in the luspatercept group showed a sustained reduction in RBC transfusion burden from baseline through week 192, with mean decreases of 6·2 RBC units (SD 5·7) during weeks 97-144 and 6·4 RBC units (4·3) during weeks 145-192. In the luspatercept group, a 33% or greater reduction in transfusion burden from baseline was observed in 173 (77%) patients over any 12-week interval and in 116 (52%) patients over any 24-week interval. The median total duration of 33% or greater transfusion burden reduction response during any period of at least 12 weeks was 586·0 days (IQR 264·0-1010·0). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) among all patients who received luspatercept (n=315, including 92 patients who crossed over after study unblinding) were anaemia (nine [3%]), increased liver iron concentration (seven [2%]), and bone pain (seven [2%]); serious TEAEs occurred in 71 (23%) patients. No treatment-related deaths occurred in any group during the study., Interpretation: These long-term results affirm luspatercept's efficacy in addressing key unmet needs of patients with transfusion-dependent β-thalassaemia with a manageable safety profile., Funding: Celgene and Acceleron Pharma., Competing Interests: Declaration of interests MDC reports honoraria or payment for lectures, presentations, speakers’ bureau, manuscript writing or educational events from Agios Pharmaceuticals, Bristol Myers Squibb, and Sanofi; receiving travel support from Sanofi; and participation on a data safety monitoring board or an advisory board for Sanofi, Silence Therapeutics, and Vertex. VV reports grants, consulting fees or contracts from Agios Pharmaceuticals, Bristol Myers Squibb/Celgene, DisperSol Technologies, IONIS Pharmaceuticals, Novartis, Pharmacosmos, Vifor Pharma, and the Government Pharmaceutical Organization (GPO). PG reports speaker's honoraria from AbbVie and AstraZeneca; and participation in safety board for Silence Therapeutics. TDC reports speaker's honoraria from Chiesi Farmaceutici; consulting fees from Agios Pharmaceuticals, Bristol Myers Squibb, and Chiesi Farmaceutici; and position as Associate Editor for the journal Blood. RO reports speaker's honoraria from Bristol Myers Squibb, Chiesi Farmaceutici, and Vertex; and board participation for Bristol Myers Squibb and Vertex. H-KL reports grants or contracts from Agios Pharmaceuticals, Bristol Myers Squibb, and Imara; and advisory board participation for Bristol Myers Squibb. L-PC reports investigator fees for clinical trial paid from Bristol Myers Squibb; and speaker's honoraria for lectures and symposium participation from Bristol Myers Squibb. KHMK reports grants or contracts from Agios Pharmaceuticals and Pfizer; consulting or advisory board participation fees from Agios Pharmaceuticals, Alexion Pharmaceuticals, Biossil, Bristol Myers Squibb, Forma Therapeutics, Novo Nordisk, Pfizer, and Vertex; speaker's honoraria from Agios Pharmaceuticals and Bristol Myers Squibb; and board participation for Sangamo. NH reports previous employment by Bristol Myers Squibb. MP reports employment by Bristol Myers Squibb. ACG reports being employed by and owning stock in Bristol Myers Squibb. YL reports being employed by and owning stock in Bristol Myers Squibb. LFM reports being employed by and owning stock in Bristol Myers Squibb. LMB reports being employed by and owning stock in Bristol Myers Squibb. AKa reports grants or contracts from Bristol Myers Squibb; speaker's honoraria from Agios Pharmaceuticals, Bristol Myers Squibb, Chiesi Farmaceutici, and Vertex; travel or meeting support from Bristol Myers Squibb; and board participation for Agios Pharmaceuticals, Bristol Myers Squibb, Vertex Pharmaceuticals, and Vifor Pharma. ATT reports support and/or consulting fees from Agios Pharmaceuticals, Bristol Myers Squibb, Novo Nordisk, Pharmacosmos, and Vifor Pharma. All other authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)