Biological Response to Bioinspired Microporous 3D-Printed Scaffolds for Bone Tissue Engineering.

The scaffold is a key element in the field of tissue engineering, especially when large defects or substitutions of pathological tissues or organs need to be clinically addressed. The expected outcome is strongly dependent on the cell-scaffold interaction and the integration with the surrounding biological tissue. Indeed, mimicking the natural extracellular matrix (ECM) of the tissue to be healed represents a further optimization that can limit a possible morphological mismatch between the scaffold and the tissue itself. For this aim, and referring to bone tissue engineering, polylactic acid (PLA) scaffolds were 3D printed with a microstructure inspired by the trabecular architecture and biologically evaluated by means of human osteosarcoma SAOS-2 cells. The cells were seeded on two types of scaffolds differing for the designed pore size (i.e., 400 and 600 µm), showing the same growth exponential trend found in the control and no significant alterations in the actin distribution. The microporous structure of the two tested samples enhanced the protein adsorption capability and mRNA expression of markers related to protein synthesis, proliferation, and osteoblast differentiation. Our findings demonstrate that 3D-printed scaffolds support the adhesion, growth, and differentiation of osteoblast-like cells and the microporous architecture, mimicking the natural bone hierarchical structure, and favoring greater bioactivity. These bioinspired scaffolds represent an interesting new tool for bone tissue engineering and regenerative medicine applications.

Essure Permanent Birth Control, Effectiveness and Safety: An Italian 11-Year Survey.

STUDY OBJECTIVE: To describe safety, tolerability, and effectiveness results through a minimum 2-year follow-up of patients who underwent permanent sterilization with the Essure insert. DESIGN: A retrospective multicenter study (Canadian Task Force classification II2). SETTING: Seven general hospitals and 4 clinical teaching centers in Italy. PATIENTS: A total of 1968 women, mean age 39.5 years (range, 23-48 years) who underwent office hysteroscopic sterilization using the Essure insert between April 1, 2003, and December 30, 2014. INTERVENTION: The women underwent office hysteroscopic bilateral Essure insert placement, with satisfactory device location and tube occlusion based on hysterosalpingography or hysterosalpingo-contrast sonography (HyCoSy). MEASUREMENTS AND MAIN RESULTS: Placement rate, successful bilateral tubal occlusion, perioperative adverse events, early postoperative (during the first 3 months of follow-up), and late complications were evaluated. Satisfactory insertion was accomplished in 97.2% of women and, in 4, perforation and 1 expulsion were detected during hysterosalpingography. Three unintended pregnancies occurred before the 3-month confirmation test. Two pregnancies were reported among women relying on the Essure inserts. Postprocedure pain was minimal and brief; in 9 women, pelvic pain became intractable, necessitating removal of the devices via laparoscopy. On telephone interviews, overall satisfaction was rated as "very satisfied" by the majority of women (97.6%), and no long-term adverse events were reported. CONCLUSION: The findings from this extended Italian survey further support the effectiveness, tolerability, and satisfaction of Essure hysteroscopic sterilization when motivated women are selected and well informed of the potential risks of the device. Moreover, the results do not demonstrate an increased incidence of complications and pregnancies associated with long-term Essure use. Patients with a known hypersensitivity to nickel may be less suitable candidates for the Essure insert.

Adaptable test bench for ASTM-compliant permeability measurement of porous scaffolds for tissue engineering.

Intrinsic permeability describes the ability of a porous medium to be penetrated by a fluid. Considering porous scaffolds for tissue engineering (TE) applications, this macroscopic variable can strongly influence the transport of oxygen and nutrients, the cell seeding process, and the transmission of fluid forces to the cells, playing a crucial role in determining scaffold efficacy. Thus, accurately measuring the permeability of porous scaffolds could represent an essential step in their optimization process. In literature, several methods have been proposed to characterize scaffold permeability. Most of the currently adopted approaches to assess permeability limit their applicability to specific scaffold structures, hampering protocols standardization, and ultimately leading to incomparable results among different laboratories. The content of novelty of this study is in the proposal of an adaptable test bench and in defining a specific testing protocol, compliant with the ASTM International F2952-22 guidelines, for reliable and repeatable measurements of the intrinsic permeability of TE porous scaffolds. The developed permeability test bench (PTB) exploits the pump-based method, and it is composed of a modular permeability chamber integrated within a closed-loop hydraulic circuit, which includes a peristaltic pump and pressure sensors, recirculating demineralized water. A specific testing protocol was defined for characterizing the pressure drop associated with the scaffold under test, while minimizing the effects of uncertainty sources. To assess the operational capabilities and performance of the proposed test bench, permeability measurements were conducted on PLA scaffolds with regular (PS) and random (RS) micro-architecture and on commercial bovine bone matrix-derived scaffolds (CS) for bone TE. To validate the proposed approach, the scaffolds were as well characterized using an alternative test bench (ATB) based on acoustic measurements, implementing a blind randomized testing procedure. The consistency of the permeability values measured using both the test benches demonstrated the reliability of the proposed approach. A further validation of the PTB's measurement reliability was provided by the agreement between the measured permeability values of the PS scaffolds and the theory-based predicted permeability value. Once validated the proposed PTB, the performed measurements allowed the investigation of the scaffolds' transport properties. Samples with the same structure (guaranteed by the fused-deposition modeling technique) were characterized by similar permeability values, and CS and RS scaffolds showed permeability values in agreement with the values reported in the literature for bovine trabecular bone. In conclusion, the developed PTB and the proposed testing protocol allow the characterization of the intrinsic permeability of porous scaffolds of different types and dimensions under controlled flow regimes, representing a powerful tool in view of providing a reliable and repeatable framework for characterizing and optimizing scaffolds for TE applications.

Advanced Electrospun Composites Based on Polycaprolactone Fibers Loaded with Micronized Tungsten Powders for Radiation Shielding.

Exposure to high levels of radiation can cause acute, long-term health effects, such as acute radiation syndrome, cancer, and cardiovascular disease. This is an important occupational hazard in different fields, such as the aerospace and healthcare industry, as well as a crucial burden to overcome to boost space applications and exploration. Protective bulky equipment made of heavy metals is not suitable for many advanced purporses, such as mobile devices, wearable shields, and manned spacecrafts. In the latter case, the in-space manufacturing of protective shields is highly desirable and remains an unmet need. Composites made of polymers and high atomic number fillers are potential means for radiation protection due to their low weight, good flexibility, and good processability. In the present work, we developed electrospun composites based on polycaprolactone (polymer matrix) and tungsten powder for application as shielding materials. Electrospinning is a versatile technology that is easily scalable at an industrial level and allows obtaining very lightweight, flexible sheet materials for wearables. By controlling tungsten powder size, we engineered homogeneous, stable and processable suspensions to fabricate radiation composite shielding sheets. The shielding capability was assessed by an in vivo model on prototype composite sheets containing 80 w% of W filler in a polycaprolactone (PCL) fibrous matrix by means of irradiation tests (X-rays) on mice. The obtained results are promising; as expected, the shielding effectivity of the developed composite material increases with the thickness/number of stacked layers. It is worth noting that a thin barrier consisting of 24 layers of the innovative shielding material reduces the extent of apoptosis by 1.5 times compared to the non-shielded mice.

Unraveling the transcriptome profile of pulsed electromagnetic field stimulation in bone regeneration using a bioreactor-based investigation platform.

INTRODUCTION: Human mesenchymal stem cells (hMSCs) sense and respond to biomechanical and biophysical stimuli, yet the involved signaling pathways are not fully identified. The clinical application of biophysical stimulation including pulsed electromagnetic field (PEMF) has gained momentum in musculoskeletal disorders and bone tissue engineering. METHODOLOGY: We herein aim to explore the role of PEMF stimulation in bone regeneration by developing trabecular bone-like tissues, and then, culturing them under bone-like mechanical stimulation in an automated perfusion bioreactor combined with a custom-made PEMF stimulator. After selecting the optimal cell seeding and culture conditions for inspecting the effects of PEMF on hMSCs, transcriptomic studies were performed on cells cultured under direct perfusion with and without PEMF stimulation. RESULTS: We were able to identify a set of signaling pathways and upstream regulators associated with PEMF stimulation and to distinguish those linked to bone regeneration. Our findings suggest that PEMF induces the immune potential of hMSCs by activating and inhibiting various immune-related pathways, such as macrophage classical activation and MSP-RON signaling in macrophages, respectively, while promoting angiogenesis and osteogenesis, which mimics the dynamic interplay of biological processes during bone healing. CONCLUSIONS: Overall, the adopted bioreactor-based investigation platform can be used to investigate the impact of PEMF stimulation on bone regeneration.

Pre-cervical ripening and hygroscopic cervical dilators in pre-labor induction.

INTRODUCTION: Induction of labor (IOL) is becoming a universal topic in Obstetrics, when the risk of continuing a pregnancy outweighs the benefits. Preinduction is a more recent tool to prepare the cervix when the BISHOP-score is low. About one-third of IOL cases require cervical ripening, which is the physical softening, thinning, and dilation of the cervix in preparation for labor and birth. We report a single center experience regarding the use of hygroscopic dilators in the pre-labor phase to obtain cervical ripening before labor induction. MATERIALS & METHODS: We conducted a retrospective observational study comparing patient records from the Gynecology and Obstetrics Unit in "Santo Stefano" Hospital in Prato, Tuscany. The inclusion criteria for participants were women who had undergone pre-labor induction because of a BISHOP-score < 3. The gestational age of all the pregnant women was at term (> 37 weeks). RESULTS: From January 2022 to April 2022, a total of 581 women delivered at term of gestational age at the Gynecology and Obstetrics Unit in "Santo Stefano" Hospital. Cervical ripening was necessary for 82 women with a Bishop score < 3 and hygroscopic cervical dilators were used in 35/82 (42.7%) patients. All patients showed a change in Bishop-score upon removal of the dilators. All 35 patients (100%) reported an increase in terms of consistency and dilation of the cervix but not in terms of length. None of the patients reported discomfort during the 24 h that they kept the hygroscopic dilators in place. No patients reported uterine tachysystole on cardiotocographic tracing, vaginal bleeding, rupture of membranes or cervical tears. CONCLUSIONS: Our results are in line with those in the literature, demonstrating the validity of hygroscopic dilators in cervical maturation of pregnancies at term and their efficacy was again highlighted in terms of both maternal and fetal safety and patient satisfaction.

Scaffold-based bone tissue engineering in microgravity: potential, concerns and implications.

One of humanity's greatest challenges is space exploration, which requires an in-depth analysis of the data continuously collected as a necessary input to fill technological gaps and move forward in several research sectors. Focusing on space crew healthcare, a critical issue to be addressed is tissue regeneration in extreme conditions. In general, it represents one of the hottest and most compelling goals of the scientific community and the development of suitable therapeutic strategies for the space environment is an urgent need for the safe planning of future long-term manned space missions. Osteopenia is a commonly diagnosed disease in astronauts due to the physiological adaptation to altered gravity conditions. In order to find specific solutions to bone damage in a reduced gravity environment, bone tissue engineering is gaining a growing interest. With the aim to critically investigate this topic, the here presented review reports and discusses bone tissue engineering scenarios in microgravity, from scaffolding to bioreactors. The literature analysis allowed to underline several key points, such as the need for (i) biomimetic composite scaffolds to better mimic the natural microarchitecture of bone tissue, (ii) uniform simulated microgravity levels for standardized experimental protocols to expose biological materials to the same testing conditions, and (iii) improved access to real microgravity for scientific research projects, supported by the so-called democratization of space.

Contrast Agents during Pregnancy: Pros and Cons When Really Needed.

Many clinical conditions require radiological diagnostic exams based on the emission of different kinds of energy and the use of contrast agents, such as computerized tomography (CT), positron emission tomography (PET), magnetic resonance (MR), ultrasound (US), and X-ray imaging. Pregnant patients who should be submitted for diagnostic examinations with contrast agents represent a group of patients with whom it is necessary to consider both maternal and fetal effects. Radiological examinations use different types of contrast media, the most used and studied are represented by iodinate contrast agents, gadolinium, fluorodeoxyglucose, gastrographin, bariumsulfate, and nanobubbles used in contrast-enhanced ultrasound (CEUS). The present paper reports the available data about each contrast agent and its effect related to the mother and fetus. This review aims to clarify the clinical practices to follow in cases where a radiodiagnostic examination with a contrast medium is indicated to be performed on a pregnant patient.

ART Innovations: Fostering Women's Psychophysical Health between Bioethics Precepts and Human Rights.

Infertility is a highly relevant global issue affecting the reproductive health of at least 15% of reproductive-aged couples worldwide. The scope and severity of the infertility problem is even more prevalent in developing countries, mostly due to untreated reproductive tract infections (RTIs). Infertility, however, goes beyond the mere inability to procreate, but brings about profound psychological, social, and ethical implications of enormous magnitude. In vitro fertilization (IVF) and other assisted reproduction technologies (ARTs) have gradually become widespread therapeutic options. After all, the implementation of medically assisted reproductive procedures in order to overcome infertility is in keeping with the tenets of the reproductive rights agenda laid out at the International Conference on Population and Development (ICPD) in Cairo in 1994. Nonetheless, concerns still linger about how to implement and regulate such interventions in an ethically tenable fashion. The unremitting pace at which such techniques develop have upset the very notion of sexuality relating to reproduction as well as the concept of family itself. That rift risks causing a crisis in terms of bioethics sustainability and enforcement, which is bound to happen when science and innovation outpace the bioethical precepts on which we rely for essential guidance in medical practice. The authors argue in favor of an approach to regulation and policy-making that puts on the forefront a thorough assessment as to potential risks that such interventions might entail for foundational bioethics principles and inalienable human rights.

Raman Spectroscopy and Aptamers for a Label-Free Approach: Diagnostic and Application Tools.

Raman spectroscopy is a powerful optical technique based on the inelastic scattering of incident light to assess the chemical composition of a sample, including biological ones. Medical diagnostic applications of Raman spectroscopy are constantly increasing to provide biochemical and structural information on several specimens, being not affected by water interference, and potentially avoiding the constraint of additional labelling procedures. New strategies have been recently developed to overcome some Raman limitations related, for instance, to the need to deal with an adequate quantity of the sample to perform a reliable analysis. In this regard, the use of metallic nanoparticles, the optimization of fiber optic probes, and other approaches can actually enhance the signal intensity compared to spontaneous Raman scattering. Moreover, to further increase the potential of this investigation technique, aptamers can be considered as a valuable means, being synthetic, short, single, or double-stranded oligonucleotides (RNAs or DNAs) that fold up into unique 3D structures to specifically bind to selected molecules, even at very low concentrations, and thus allowing an early diagnosis of a possible disease. Due to the paramount relevance of the topic, this review focuses on the main Raman spectroscopy techniques combined with aptamer arrays in the label-free mode, providing an overview on different applications to support healthcare management.

Thrombin Assessment on Nanostructured Label-Free Aptamer-Based Sensors: A Mapping Investigation via Surface-Enhanced Raman Spectroscopy.

Aptamers, synthetic single-stranded DNA or RNA molecules, can be regarded as a valuable improvement to develop novel ad hoc sensors to diagnose several clinical pathologies. Their intrinsic potential is related to the high specificity and sensitivity to the selected target biomarkers, being capable of detecting very low concentrations and thus allowing an early diagnosis of a possible disease. This kind of probe can be usefully integrated into a number of different devices in order to provide a reliable acquisition of the analyte and properly elaborate the related signal. The study presents the fabrication and characterization of a label-free aptamer sensor designed using a gold-coated silicon nanostructured substrate to map the target molecule by means of surface-enhanced Raman spectroscopy (SERS). As a proof, thrombin was used as a model at four different concentrations (i.e., 0.0873, 0.873, 8.73, and 87.3 nM). SERS mapping analysis was carried out considering each representative band of the aptamer-thrombin complex (centered at 822, 1140, and 1558 cm-1) and then combining them in order to acquire a comprehensive and unambiguous measure of the target. In both cases, a valuable correlation was evaluated, even if the first approach can suffer from some limitations in the third band related to lower definition of the characteristic peak compared to those in the other two bands.