This review addresses the convergence of 3D bioprinting with artificial intelligence (AI) and machine learning (ML) as a new frontier in healthcare to revolutionize personalized medicine. The article first discusses several key components such as pre-printing, material selection, post-printing, and role of AI/ML algorithms during the printing process by predicting tissue construct outcomes and optimizing bioprinting parameters. It follows with discussion of applications of AI-integrated 3D bioprinting such as for drug testing models, surgical planning, and the production of regenerative combination therapies. Finally, it discussed several challenges including ethics, data privacy and security, and governmental regulations in the field of AI driven bioprinting process. By leveraging AI within the 3D bioprinting process, healthcare practitioners can enhance bioprinting fidelity and automate error corrections. Overall, there are several key components of AI-driven bioprinting, including aspects of pre-printing, material selection, and post-printing. AI/ML algorithms can play a vital role during the printing process by predicting tissue construct outcomes and optimizing bioprinting parameters. Additionally, cybersecurity measures, including blockchain and secure networks, are essential to safeguard the bioprinting process against potential threats. Applications of AI-integrated 3D bioprinting include drug testing models, surgical planning, and the production of regenerative combination therapies. Despite the potential of integrating AI and 3D bioprinting in healthcare, several challenges have been identified, including ethics, data privacy and security, and governmental regulations. This review highlights the promise of AI in healthcare, which is vast, and aims to understand its potential for the 3D bioprinting area. AI requires robust governance frameworks, ethical standards, and interdisciplinary collaboration to ensure responsible innovation, transparency, and regulatory alignment. By addressing these considerations, scientistswill be critical to accelerate AI driven bioprinting and deliver impactful, patient-centered solutions in the future.

Microchannels possess enhanced thermal convection due to its greater surface-to-volume ratio. Empirical evidence depicts that flows in microchannels are an effective means of dissipating heat flux from small, localized heat source points over a larger surface area. It formulates symmetric heat distribution, holding promising applications for tiny biological regulators. The size, shape, structures, and density distribution of heat sources in microchannels greatly influence heat distribution, whereas the medium of heat transfer was found to have a marginal effect in the case of a minute viscosity difference between two fluids. The thermo-fluid coupling effects in microchannels are highlighted to evaluate the modulation of temperature and variations of velocity within the working fluid. The effect of heat distributions on fluid flow in the presence of micro-fins within a microchannel was studied numerically in the presence of both Newtonian and non-Newtonian fluid, while considering the case of two different fin configuration conditions, i.e., decreasing inter-fin distance with decreasing fin height, and increasing inter-fin distance with increasing fin height. The flow domain was considered to have inlet boundary conditions: pulsatile flow (time varying inlet velocity and fin's temperature). Whereas, fins of different shapes: rectangular, elliptical, and conical shapes, were considered in the study. The local Nusselt number was found to be influenced by the effective surface area and boundary layer thickness linked to the varied micro-fin structures, as well as the pressure drop caused by the varying fin separation lengths. In the case of decreasing inter-fin distance, the highest Nu was found to be 30.41 and the lowest Nu was found to be 7.19 for non-Newtonian fluid for conical fins. In the case of increasing inter-fin distance, the highest Nu was found to be 30.40 and the lowest Nu was found to be 7.20 for non-Newtonian fluid for conical fins.

The purpose of this review is to share insights from recognized experts in 3D biopriniting on the recent advances in these technologies discussed during a recent workshop held in conjunction with the 2024 ISS National Laboratory Research and Development Conference (ISSRDC). We seek to answer how microgravity can be used as a disruptor to make further advances not possible through conventional means. This review will cover current efforts underway to use microgravity for 3D bioprinting. For instance multi-levitation biofabrication technology funded under the EU PULSE project is currently being used to create cardiovascular 3D in vitro models to better mimic cardiac and vascular physiology compared to organoids. These types of models could be expanded to other organ systems and disease models to use the environment of microgravity to unlock new signaling pathways to cure disease. The major takeaway from this review is that microgravity will unlock new opportunities for 3D bioprinting that were simply not possible using conventional means. We provide forward looking answers to what microgravity will inspire from advanced biomaterials to new disease models to even creating a knowledge hub for 3D bioprinting to launch new platforms at record speeds.

Traumatic brain injury (TBI), particularly among military personnel, poses significant challenges in acute management and long-term outcomes. Difficult-to-diagnose autoregulatory and inflammatory changes lead to neurocognitive impairment, anxiety, sleep disturbance, and chronic pain. To optimize readiness and test therapeutics for both diagnostic and future TBI treatments, this feasibility study introduces a novel wearable multimodal platform that integrates photoplethysmography and infra-red (IR) sensing from a camera and a wearable sensor to detect vital signs and then leverages machine learning (ML) to predict the need for acute treatment. This prospective observational study involving 28 healthy volunteers simulated a triage emergency room workflow to test sensor accuracy and mobile app functionality. The wearable device demonstrated high accuracy in pulse rate (mean error 7.3%) and oxygen saturation (mean error -1.2%) compared to standard-of-care devices. Camera-based pulse and respiratory rate, and wearable pulse, oxygen, and temperature sensing were tested in a mock triage setting to simulate activation of light-based treatment upon detection of physiological changes of concern after acute TBI. Preliminary ML models to predict hypotension and pain based on retrospective data achieved 98.4% and 93% accuracy but showed limitations in prospective real-time applications. This study provided insights to prepare for future iterations that will integrate near-IR spectroscopy to detect cerebral oximetry, and quantum dot light-emitting diodes to activate light-based treatment (photobiomodulation) from within a wearable head dressing. The findings underscore the potential of this platform to bridge critical gaps in acute TBI care through early detection and future therapeutic intervention. Further development is needed to address environmental challenges, improve accuracy across diverse populations, and refine the device for real-time clinical use. This innovative approach has the potential to revolutionize TBI care by bridging current gaps in diagnostic and therapeutic management.

The viscosity of fluid plays a major role in the flow dynamics of microchannels. Viscous drag and shear forces are the primary tractions for microfluidic fluid flow. Capillary blood vessels with a few microns diameter are impacted by the rheology of blood flowing through their conduits. Hence, regenerated capillaries should be able to withstand such impacts. Consequently, there is a need to understand the flow physics of culture media through the lumen of the substrate as it is one of the vital promoting factors for vasculogenesis under optimal shear conditions at the endothelial lining of the regenerated vessel. Simultaneously, considering the diffusive role of capillaries for ion exchange with the surrounding tissue, capillaries have been found to reorient themselves in serpentine form for modulating the flow conditions while developing sustainable shear stress. In the current study, S-shaped (S1) and delta-shaped (S2) serpentine models of capillaries were considered to evaluate the shear stress distribution and the oscillatory shear index (OSI) and relative residual time (RRT) of the derivatives throughout the channel (due to the phenomena of near-wall stress fluctuation), along with the influence of culture media rheology on wall stress parameters. The non-Newtonian power-law formulation was implemented for defining rheological viscosity of the culture media. The flow actuation of the media was considered to be sinusoidal and physiological, realizing the pulsatile blood flow behavior in the circulatory network. A distinct difference in shear stress distributions was observed in both the serpentine models. The S1 model showed higher change in shear stress in comparison to the S2 model. Furthermore, the non-Newtonian viscosity formulation was found to produce more sustainable shear stress near the serpentine walls compared to the Newtonian formulation fluid, emphasizing the influence of rheology on stress generation. Further, cell viability improved in the bending regions of serpentine channels compared to the long run section of the same channel.

Fibroblast cell migration plays a crucial role in the wound-healing process. Hence, its quantitative investigation is important to understand the mechanism of the wound-healing process. The dynamic nature of the wound-healing process can be easily implemented using a microfluidic-based wound-healing assay. This work presented the use of a microfluidics device to simulate traumatic wounds on fibroblast cell monolayers by utilizing trypsin flow and PDMS barrier. In this study, a microfluidic chip with a transparent silk film is reported. The placement of film provides 3D cell culture conditions that mimic a 3D extracellular matrix (ECM) like environment and allows real-time monitoring of cells. A numerical study was conducted to evaluate the influence of dynamic medium-induced shear stress on the base and wall of the microchannel. This could facilitate the optimization of the inlet flow conditions of the media in the channel. At the same time, it could help in identifying stress spots in the channel. The scaffolds were placed in those spots for evaluating the influence of shear forces on the migratory behavior of fibroblast cells. The in vitro microfluidic assembly was then evaluated for cell migration under the influence of external shear forces during the wound-healing phenomena. A faster wound healing was obtained at the end of 24 h of the creation of the wound in the presence of optimal shear stress. On increasing the shear stress beyond a threshold limit, it dissociates fibroblast cells from the surface of the substrate, thereby decelerating the wound-healing process. The above phenomena were transformed in both coplanar microfluidics surfaces (by realizing in the multichannel interlinked model) and transitional microfluidics channels (by realizing in the sandwich model).

The application of 3D printing technologies fields for biological tissues, organs, and cells in the context of medical and biotechnology applications requires a significant amount of innovation in a narrow printability range. 3D bioprinting is one such way of addressing critical design challenges in tissue engineering. In a more general sense, 3D printing has become essential in customized implant designing, faithful reproduction of microenvironmental niches, sustainable development of implants, in the capacity to address issues of effective cellular integration, and long-term stability of the cellular constructs in tissue engineering. This review covers various aspects of 3D bioprinting, describes the current state-of-the-art solutions for all aforementioned critical issues, and includes various illustrative representations of technologies supporting the development of phases of 3D bioprinting. It also demonstrates several bio-inks and their properties crucial for being used for 3D printing applications. The review focus on bringing together different examples and current trends in tissue engineering applications, including bone, cartilage, muscles, neuron, skin, esophagus, trachea, tympanic membrane, cornea, blood vessel, immune system, and tumor models utilizing 3D printing technology and to provide an outlook of the future potentials and barriers.

3D bioprinting has emerged as a tool for developing in vitro tissue models for studying disease progression and drug development. The objective of the current study was to evaluate the influence of flow driven shear stress on the viability of cultured cells inside the luminal wall of a serpentine network. Fluid–structure interaction was modeled using COMSOL Multiphysics for representing the elasticity of the serpentine wall. Experimental analysis of the serpentine model was performed on the basis of a desirable inlet flow boundary condition for which the most homogeneously distributed wall shear stress had been obtained from numerical study. A blend of Gelatin-methacryloyl (GelMA) and PEGDA200 PhotoInk was used as a bioink for printing the serpentine network, while facilitating cell growth within the pores of the gelatin substrate. Human umbilical vein endothelial cells were seeded into the channels of the network to simulate the blood vessels. A Live-Dead assay was performed over a period of 14 days to observe the cellular viability in the printed vascular channels. It was observed that cell viability increases when the seeded cells were exposed to the evenly distributed shear stresses at an input flow rate of 4.62 mm/min of the culture media, similar to that predicted in the numerical model with the same inlet boundary condition. It leads to recruitment of a large number of focal adhesion point nodes on cellular membrane, emphasizing the influence of such phenomena on promoting cellular morphologies.

Cerebral blood flow (CBF) dysregulation has been implicated in a wide variety of conditions. Cerebrovascular reactivity (CVR) to CO2 may be a biomarker of CBF dysregulation. NIRS-measured regional cerebral tissue oxygen saturation (rSO2) is a non-invasive measurement made with portable and relatively inexpensive devices. We previously reported that monitoring rSO2 can identify changes in cerebrovascular dynamics in response to hypercapnic breathing challenges. The present study builds on this work, employing rSO2 to characterize changes in CBF correlates during hypercapnic breathing challenges, with a new focus on correlations with NIRS-measured vital signs. A custom breathing circuit was used to deliver a series of hypercapnic breathing challenges and recovery periods to healthy young adult subjects grouped into three exercise factors. Change in rSO2 from intra- to pre-challenge (ΔrSO2) correlated positively with change in heart rate (ΔHRhyp). Athletes showed higher ∆HRhyp than casual and non-exercisers. We previously established that athletes showed higher ΔrSO2 responses to hypercapnic breathing challenges. While the relationships between ΔrSO2 and ΔHRhyp and change in end tidal CO2 (ΔPETCO2) in response to hypercapnic breathing challenges appears to be in tact in the healthy young adults studied, and more pronounced in athletes, these relationships may not be preserved in cases of compromised CVR. Change in respiration rate correlated negatively with ΔPETCO2. Establishing baseline values of rSO2, PETCO2, HR, and RR may be useful in identifying changes in an individual’s CVR. Combined monitoring of rSO2, PETCO2, HR, and RR presents a portable, inexpensive, noninvasive NIRS-based modality for detecting changes in cerebrovascular health.

Understanding of the thermochemical stability of Mg-2(Si,Sn) thermoelectric materials is crucial for their applicability in thermoelectric modules. A miscibility gap was reported for the quasi-binary Mg2Si-Mg2Sn series and the exact compositions of its limits are disputed. In this work we study the phase evolution and stability of Mg2SixSn1-x with x = 0.5. Samples were annealed at 600 degrees C, 525 degrees C, and 450 degrees C both with and without excess elemental Mg in quartz ampules in order to manipulate the Mg vapor pressure. This led to two qualitatively different evolution routes of phase constitution, namely, (I) progressive phase separation and material degradation related to intense Mg loss accompanied by formation of side phases such as elemental Si and (II) much slower phase separation without formation of elemental precipitates when the sample was kept under Mg vapor atmosphere. Accordingly, XRD and EDAX gave evidence that the phase evolution and demixing behavior in magnesium silicide stannide depend sensitively on the amount and rate of Mg loss. We also observe stabilization of solid solutions against demixing by coherency strain and can show that the phase separation which will occur in thermodynamic equilibrium due to the miscibility gap, can be inhibited if Mg loss is suppressed. Then Mg2Si0.5Sn0.5 shows improved stability at typical application temperatures (450 - 600 degrees C) which are far below the previously reported upper limit of the coherent miscibility gap (720 degrees C). The improvement of the phase stability of thermoelectric Mg 2 (Si,Sn) by controlling the Mg vapor pressure is of essential importance for long-term utilization of the material in thermogenerators at elevated temperatures. (C) 2021Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

MicroRNAs (miRNAs) are potent regulators of multiple biological processes. Previous studies have demonstrated that miR-146a-5p increases in normal mice during aging, while long-living Ames dwarf (df/df) mice maintain youthful levels of this miRNA. The aim of this study was to elucidate the involvement of miR-146a-5p in modulating cellular senescence and apoptosis in visceral adipose tissue of df/df mice and cultured pre-adipocytes. To test the effects of miR-146a-5p overexpression on visceral adipose tissue, wild-type, and df/df mice, were treated with miRNA-negative control-base and df/df were transfected with 4 or 8 µg/g of a miR-146a-5p mimetic, respectively. Effects of miR-146a-5p overexpression were also evaluated in 3T3-L1 cells cultured under high and normal glucose conditions. Treatment with miR-146a-5p mimetic increased cellular senescence and inflammation and decreased pro-apoptotic factors in visceral adipose tissue of df/df mice. The miR-146a-5p mimetic induced similar effects in 3T3-L1 cells cultivated at normal but not high glucose levels. Importantly, 3T3-L1 HG cells in high glucose conditions showed significantly higher expression of miR-146a-5p than 3T3-L1 grown in normal glucose conditions. These results indicate that miR-146a-5p can be a marker for cellular senescence. This miRNA represents one of the significant SASP factors that if not precisely regulated, can accentuate inflammatory responses and stimulate senescence in surrounding non-senescent cells. The role of miR-146a-5p is different in healthy versus stressed cells, suggesting potential effects of this miRNA depend on overall organismal health, aging, and metabolic state.

According to recent investigations on p-type Mg2X (X = Si, Sn, Ge), p-type Mg2Ge is found to be far superior to the p-type binaries while having thermoelectric properties comparable to the best solid solutions of p-type Mg-2(Si,Sn). The unexpectedly good properties are supposedly due to a nonrigid band structure with a temperature-dependent interband separation. Further optimization can be expected by alloying Si or Sn into the Ge site to lower the thermal conductivity, thereby increasing the figure of merit. Here, solid solutions of p-type Mg2Ge1-xSnx and p-type Mg2Ge1-zSiz with x, z = 0.1 and 0.2 are successfully synthesized via ball milling. The thermal conductivities are significantly reduced throughout the whole temperature range by around 30% due to the alloying effect. The electronic properties of all Ge-rich samples show similar temperature-dependent behavior to p-type Mg2Ge. For the Mg-2(Ge,Sn) systems, a compensation of reduced thermal conductivity and decreased carrier mobility are found, leading to zT values comparable to p-type Mg2Ge. Whereas for the Si containing samples, a thermoelectric figure of merit zT of 0.49 +/- 0.07 at 675 K for z = 0.1 is achieved, the highest reported so far for the p-type Mg-2(Ge,Si) systems and a zT(avg) that is 30% higher than that of binary Mg2Ge.

Hydrogels such as alginate and gelatin have shown potential as biomaterials in various three-dimensional (3D) bioprinting applications. However, parameters such as viscosity, porosity, and printability influence the performance of hydrogel-based biomaterials, and there are limited characterization studies conducted on the behavior of these constructs. In this work, a syringe-based extrusion bioprinter was used to print 3D constructs with bioink composed of various concentrations of alginate and gelatin along with fibrinogen and human umbilical vein endothelial cells. Instead of crosslinking the gelatin, the gelatin was left uncrosslinked to provide microporosity within the system that can impact the cellular response. Mechanical and biochemical characterization was performed to evaluate the structural stability and integrity of the printed constructs along with viability of embedded cells. Bioprinted constructs of a higher total concentration of alginate and gelatin yielded better stability and structural integrity after culture. More importantly, higher amounts of gelatin (i.e., 1:9 instead of 2:3 alginate:gelatin) were shown to improve printability, which is different than most studies that instead use alginate to improve printability. In addition, higher amounts of gelatin impacted the changes in surface morphological features of the constructs after incubation, and ultimately improved biocompatibility with our system. Overall, this study demonstrated that an uncrosslinked gelatin system can provide flexible printing parameters and surface morphologies, but careful control over the printing parameters may be required. The bioink concentration of 10% (w/v) with minimum alginate and higher gelatin concentration exhibited the best printability, cell survival, and viability.

Cardiovascular problems are common side effects of cancer therapy, and the heart is one of the major organs that are of concern for potential damage following radiation exposure. Radiation directly affects biological molecules. However, the most impact of radiation‐mediated cell death derives from the generated free radicals, which increase oxidative stress. Reactive oxygen species (ROS) are a hallmark in cardiovascular diseases (CVD), mainly because of its interplay with nitric oxide (NO). NO offers cardioprotection against ROS‐induced damage and ROS, in turn, limits the beneficial effects of NO. Furthermore, radiation induces adaptive alterations in the vasculature leading to vascular dysfunction. Although pathways triggering cardiovascular damage following radiation exposure involve vascular damage in humans, the long‐term mechanisms by which radiation‐induced oxidative stress affects the heart have not yet been clearly defined. We hypothesized that increased ROS contribute to long‐term heart damage following radiation exposure. Flash frozen heart (apex) samples from male C5BL/6J mice (5 months) sacrificed nine months' post radiation was provided by the Department of Surgery at Duke University. Briefly, live animals were subjected to whole body radiation (dose: 200 cGy) at the Brookhaven National Lab. Control animals received Sham treatment. Transverse sections (10 μm) of heart from irradiated and non‐irradiated mice were obtained in a cryostat. Representative images of cardiac fibers were revealed with H&E staining. Additionally, ROS and NO production were evaluated by confocal microscopy. Briefly, the fluorescent probes, Dihydroethidium (DHE) and DAF‐FM Diacetate, were diluted in PBS (5 μM) and the samples were incubated in a humidified chamber at 37° C for 30 minutes. Slides were imaged using a 20x objective and analyzed using ImageJ software (NIH, Bethesda, MD, USA). Protein expression for NOS isoforms was also assessed using a standard Western blotting technique. Our histological analysis indicates loss of cardiac tissue (heart ‐ apex) in irradiated animals compared to Sham animals, suggestive of anatomical remodeling. Confocal microscopy showed an increase in intracellular ROS in irradiated tissue (n=5; p≤0.05), but no significant difference was observed in NO production (n=5; p>0.05). Different NOS isoforms evaluation showed elevated iNOS protein expression levels in irradiated animals. In conclusion, gamma radiation stimulates sustained ROS production in heart tissue and activation of iNOS might be a mechanism for counterbalancing the disruption in the heart antioxidant response system.Support or Funding InformationNASA Florida space Grant Consortium 2018This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Mg2Si based materials are attractive candidates for mid-temperature (hot side around 800 K) thermoelectric generators (TEG). A crucial component of a TEG module is the diffusion barrier layer, which prevents the inter-diffusion between the thermoelectric (TE) material and the metal interconnect at the hot junction. Previous reports indicate that elemental nickel is a suitable diffusion-barrier (DB) layer material in Mg2Si. The contact between the DB layer and the TE material is usually made using the monoblock sintering technique, which is a single-step compaction cum contacting method. Monoblock sintering of Ni/Mg2Si has been reported with the compaction carried out using a current assisted hot-pressing technique. Alternatively, induction assisted hot-pressing can be a low-cost, scalable alterative for monoblock sintering of Ni/Mg2Si. Bi doped Mg2Si was synthesized using induction melting of the constituent elements in an inert argon atmosphere. The obtained ingot was hand crushed and the TE powder sandwiched between nickel foils. The compacting was carried out in an induction assisted hot-uniaxial press. The contact interface was probed using scanning electron microscopy (SEM) along with energy dispersive x-ray spectroscopy. SEM images indicate good adhesion along with the formation of an intermediate layer between nickel and Mg2Si with distinct phases of Ni-Si-Mg combinations. Integral contact resistance measurements indicate an Ohmic contact with excellent contact resistance (rc) value of ∼ 14 μΩ cm2.

Over the last few years, significant advances have been made in the field of additive manufacturing and three-dimensional (3D) printing which has impacted health care industry in a major way. Manufacturers and medical device researchers are using additive manufacturing technology to develop: (a) 3D-printed models and prototypes for presurgical planning and patient education, (b) new designs of medical devices which could not be fabricated using traditional manufacturing techniques, and (c) implantable and nonimplantable medical devices that are designed for the anatomy of a specific patient. In the future, the advancements made in the additive manufacturing technology might enable the clinicians, surgeons, and radiologists to personalize and print on demand medical implants (with appropriate regulatory oversight) that meet the needs of individual patients. Another exciting advance in additive manufacturing is bioprinting which involves the 3D printing of human tissues by depositing cells layer-by-layer to grow organs. Some of the challenges in bioprinting that need to be addressed include cell mapping and sourcing for organ function, development of bio-ink recipes, vascularization of bioprinted structures, bioprinter technologies, and characterization of bioprinted structures.The focus of this Special Issue is on novel additive manufacturing methods that are relevant to 3D printing of medical devices, performance testing of 3D-printed test devices, bioprinting, and the performance and safety challenges related to long-term durability of implantable 3D-printed devices.As Guest and Associate Editors, we would like to greatly thank the authors and co-authors for their valuable contributions and the reviewers for the time and efforts. Over 20 full-length research papers and technical briefs were submitted to the Special Issue, many of which were accepted for publication after undergoing the peer-review process. A very special thanks to Co-editor Professor Rupak Banerjee, for his inspiring guidance and patience over the past several months as we complete the peer-review process. We will also like to thank Professor William Durfee for his help in organizing the review tracking process. We would also like to thank the ASME editorial staff for their fantastic technical support. We sincerely hope that the ASME Journal of Medical Device community will enjoy this Special Issue.Kunal MitraPrasanna Hariharan