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Introduction: Intensive research is dedicated to the development of novel biomaterials and medical devices to be used as grafts in reconstructive surgery, with the purpose of enhancing their therapeutic effectiveness, safety, and durability. A variety of biomaterials, from autologous bone to polymethylmetacrylate, polyether ether ketone, titanium, and calcium-based ceramics are used in cranioplasty. Porous hydroxyapatite (PHA) is reported as a possible material for bone reconstruction, with good signs of biocompatibility, osteoconductive and osteointegrative properties. In the present paper we studied the possible antibacterial properties of PHA in a laboratory test in order to provide a possible overview of the occurrence of post-operative infections in PHA cranioplasty. Method: The test method has been designed to evaluate the potential antimicrobial activity of specimens under dynamic contact conditions to overcome difficulties in ensuring contact of inoculum to the specimen surface. The test was conducted using Staphylococcus aureus ATCC6538 as a bacterial strain. Results: Two experimental sets were performed to evaluate the antimicrobial properties of the specimens against two different Staphylococcus aureus concentrations. The first preliminary test (a) verified the antibacterial property at 0, 1, 2, and 4 h of contact time; the second confirmatory test (b) was repeated to verify the antibacterial property at 0, 4, 8 h. In the first experiment, after the first hour of contact, the bacterial inoculum was reduced by 7.96% compared to "inoculum only," which increased to 26.11% at the second hour, and up to 52.33% after 4 h. In the second experiment, the confirmation test showed that bacterial growth reaches maximum inhibition after 4 h of contact. At 4 h, there was a higher bacterial reduction of 72.93%, which decreased at 8 h (36.45%). Conclusion: Analyzing the growth trend of viable microorganisms under Dynamic Contact Conditions it can be seen that PHA cranioplasty appears to inhibit exponential growth by inducing bacterial stasis in the early hours of contact, reaching a maximum reduction within 4 h, in this adopted experimental condition. [ABSTRACT FROM AUTHOR]

Calcium phosphate nanoparticles (CaP NPs) are an efficient class of nanomaterials mainly used for biomedical applications but also very promising in other sectors such as cosmetics, catalysis, water remediation, and agriculture. Unfortunately, as in the case of other nanomaterials, their wide application is hindered by the difficulty to control size, morphology, purity and degree of particle aggregation in the translation from laboratory to industrial scale production that is usually carried out in batch or semi-batch systems. In this regard, the use of continuous flow synthesis can help to solve this problem, providing more homogenous reaction conditions and highly reproducible synthesis. In this paper, we have studied with a design of experiment approach the precipitation of citrate functionalized CaP NPs aided by sonication using a continuous flow wet chemical precipitation, and the effect of some of the most relevant process factors (i.e., reactant flow rate, sonication amplitude, and maturation time) on the physico-chemical properties of the NPs were evaluated. From the statistical data analysis, we have found that CaP NP dimensions are influenced by the reactor flow rate, while the crystalline domain dimensions and product purity are influenced by the maturation process. This work provides a deeper understanding of the relationships between reaction process factors and CaP NP properties, and is a relevant contribution for the scale-up production of CaP NPs for nanomedical or other applications. [ABSTRACT FROM AUTHOR]

The lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking. In this study, the authors sought to assess tolerability and efficacy of an inhalable lung-to-heart nano-in-micro technology (LungToHeartNIM) for cardiac-specific targeting of a mimetic peptide (MP), a first-in-class for modulating impaired L-type calcium channel (LTCC) trafficking, in a clinically relevant porcine model of HF. Heart failure with reduced ejection fraction (HFrEF) was induced in Göttingen minipigs by means of tachypacing over 6 weeks. In a setting of overt HFrEF (left ventricular ejection fraction [LVEF] 30% ± 8%), animals were randomized and treatment was started after 4 weeks of tachypacing. HFrEF animals inhaled either a dry powder composed of mannitol-based microparticles embedding biocompatible MP-loaded calcium phosphate nanoparticles (dpCaP-MP) or the LungToHeartNIM only (dpCaP without MP). Efficacy was evaluated with the use of echocardiography, invasive hemodynamics, and biomarker assessment. DpCaP-MP inhalation restored systolic function, as shown by an absolute LVEF increase over the treatment period of 17% ± 6%, while reversing cardiac remodeling and reducing pulmonary congestion. The effect was recapitulated ex vivo in cardiac myofibrils from treated HF animals. The treatment was well tolerated, and no adverse events occurred. The overall tolerability of LungToHeartNIM along with the beneficial effects of the LTCC modulator point toward a game-changing treatment for HFrEF patients, also demonstrating the effective delivery of a therapeutic peptide to the diseased heart. [Display omitted] [ABSTRACT FROM AUTHOR]