Controlling Biomedical Devices Using Pneumatic Logic.

Many biomedical devices are powered and controlled by electrical components. These electronics add to the cost of a device (possibly making the device too expensive for use in resource-limited or point-of-care settings) and can also render the device unsuitable for use in some environments (for example, high-humidity areas such as incubators where condensation could cause electrical short circuits, ovens where electronic components may overheat, or explosive or flammable environments where electric sparks could cause serious accidents). In this work, we show that pneumatic logic can be used to power and control biomedical devices without the need for electricity or electric components. Originally developed for controlling microfluidic "lab-on-a-chip" devices, these circuits use microfluidic valves like transistors in air-powered logic "circuits." We show that a modification to the basic valve design-adding additional air channels in parallel through the valve-creates a "high-flow" valve that is suitable for controlling a broad range of bioinstruments, not just microfluidics. As a proof-of-concept, we developed a high-flow pneumatic oscillator that uses five high-flow Boolean NOT gates arranged in a loop. Powered by a single constant vacuum source, the oscillator provides five out-of-phase pneumatic outputs that switch between vacuum and atmospheric pressure every 1.3 s. Additionally, a user can adjust the frequency of the oscillator by squeezing a bellows attached to one of the pneumatic outputs. We then used the pneumatic oscillator to power a low-cost 3D-printed laboratory rocker/shaker commonly used to keep blood products, cell cultures, and other heterogeneous samples in suspension. Our air-powered rocker costs around $12 USD to build and performs as well as conventional electronic rockers that cost $1000 USD or more. This is the first of many biomedical devices that can be made cheaper and safer using pneumatic logic.

Flexible multimaterial fibers in modern biomedical applications.

Biomedical devices are indispensable in modern healthcare, significantly enhancing patients' quality of life. Recently, there has been a drastic increase in innovations for the fabrication of biomedical devices. Amongst these fabrication methods, the thermal drawing process has emerged as a versatile and scalable process for the development of advanced biomedical devices. By thermally drawing a macroscopic preform, which is meticulously designed and integrated with functional materials, hundreds of meters of multifunctional fibers are produced. These scalable flexible multifunctional fibers are embedded with functionalities such as electrochemical sensing, drug delivery, light delivery, temperature sensing, chemical sensing, pressure sensing, etc. In this review, we summarize the fabrication method of thermally drawn multifunctional fibers and highlight recent developments in thermally drawn fibers for modern biomedical application, including neural interfacing, chemical sensing, tissue engineering, cancer treatment, soft robotics and smart wearables. Finally, we discuss the existing challenges and future directions of this rapidly growing field.

Synergistic potential of stem cells and microfluidics in regenerative medicine.

Regenerative medicine has immense potential to revolutionize healthcare by using regenerative capabilities of stem cells. Microfluidics, a cutting-edge technology, offers precise control over cellular microenvironments. The integration of these two fields provides a deep understanding of stem cell behavior and enables the development of advanced therapeutic strategies. This critical review explores the use of microfluidic systems to culture and differentiate stem cells with precision. We examined the use of microfluidic platforms for controlled nutrient supply, mechanical stimuli, and real-time monitoring, providing an unprecedented level of detail in studying cellular responses. The convergence of stem cells and microfluidics holds immense promise for tissue repair, regeneration, and personalized medicine. It offers a unique opportunity to revolutionize the approach to regenerative medicine, facilitating the development of advanced therapeutic strategies and enhancing healthcare outcomes.

Contact Dermatitis From Biomedical Devices, Implants, and Metals-Trouble From Within.

Allergic contact dermatitis is characterized by its appearance of red, raised and infiltrated, scaling or scabbed skin and intense pruritus, and distinguished from irritant contact dermatitis by its specific immune process and histopathology. Many contact allergens are low-molecular- weight chemicals including metals such as nickel, cobalt, and chromium, preservatives, and adhesives. When such materials are used internally in biomedical devices, they are similarly capable of causing sensitization and an inflammatory response. Sometimes, the reaction remains internal, and presents as swelling, pain, stiffness, decreased range of motion, and internal itching around the implant. Such reactions may, in some cases, also extend to include a localized or, rarely, systemic contact dermatitis indicative of the same process. This review will present an overview of reported skin and local internal reactions to orthopedic implants, which are the largest category of implanted internal metal devices. Immune reactions to smaller categories of medical appliances include cardiac devices and vascular stents, neuromodulation devices, diabetic appliances, Nuss bar surgery for pectus excavatum, and dental and spinal implants. We will review the available diagnostic tools, the consensus on interpretation, and reported strategies for treatment.

Inspiring a convergent engineering approach to measure and model the tissue microenvironment.

Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics of the TiME in unprecedented detail; however, many advances still occur in silos that rarely integrate information to study the TiME in its full detail. This review provides an integrative overview of the engineering principles underlying chemical, optical, electrical, mechanical, and computational science to probe, sense, model, and fabricate the TiME. In individual sections, we first summarize the underlying principles, capabilities, and scope of emerging technologies, the breakthrough discoveries enabled by each technology and recent, promising innovations. We provide perspectives on the potential of these advances in answering critical questions about the TiME and its role in various disease and developmental processes. Finally, we present an integrative view that appreciates the major scientific and educational aspects in the study of the TiME.

Incorporating a Hands-On Device-Based Activity in a Human Factors Biomedical Engineering Course in Sub-Saharan Africa.

A challenge in building the biomedical engineering human factors course at Malawi University of Business and Applied Sciences was integrating meaningful direct experiences with medical products. The instructor also noticed a significant gap between the topics in the course and their surrounding clinical context, a low-income setting. Recognizing that devices should be designed and evaluated in the context of the local users' needs and situations, new hands-on modules were created and implemented in this BME human factors course. Students were asked to critically evaluate and make recommendations to improve the human factors aspects of the software and hardware of the IMPALA, a vital signs monitoring device developed for use in Malawi. Engaging with this medical device, students observed and understood many issues discussed in human factors, including the design of ports, controls, and other user interfaces. The collaboration between the course and the IMPALA project harnessed the local expertise of students to improve the design of a new patient monitoring system. Thus, the IMPALA project itself benefited from this collaboration. Second, students greatly benefited from applying the class concepts to the IMPALA. Students were engaged far more during the interactive components than during the lecture components. Many students successfully translated their knowledge on human factors to their final-year design project.

Artificial urinary bladder model.

Technological advancements in the medical field are often slow and expensive, sometimes due to complexities associated with pre-clinical testing of medical devices and implants. There is therefore a growing need for new test beds that can mimic more closely the in vivo environment of physiological systems. In the present study, a novel bladder model was designed and fabricated with the aim of providing a pre-clinical testing platform for urological stents and catheters. The model is collapsible, has a Young's modulus that is comparable to a biological bladder, and can be actuated on-demand to enable voiding. Moreover, the developed fabrication technique provides versatility to adjust the model's shape, size, and thickness, through a rapid and relatively inexpensive process. When compared to a biological bladder, there is a significant difference in compliance; however, the model exhibits cystometry profiles during priming and voiding that are qualitatively comparable to a biological bladder. The developed bladder model has therefore potential for future usage in urological device testing; however, improvements are required to more closely replicate the architecture and relevant flow metrics of a physiological bladder.

Spinning the Future: The Convergence of Nanofiber Technologies and Yarn Fabrication.

The rapid advancement in nanofiber technologies has revolutionized the domain of yarn materials, marking a significant leap in textile technology. This review dissects the nexus between cutting-edge nanofiber technologies and yarn manufacturing, aiming to illuminate the pathway toward engineering advanced textiles with unparalleled functionality. It first discusses the fundamentals of nanofiber assemblies and spinning techniques, primarily focusing on electrospinning, centrifugal spinning, and blow spinning. Additionally, the study delves into integrating nanofiber spinning technologies with traditional and modern yarn fabrication principles, elucidating the design principles that underlie the creation of yarns incorporating nanofibers. Twisting technologies are explored to examine how they can be optimized and adapted for incorporating nanofibers, thus enabling the production of innovative nanofiber-based yarns. Special attention is given to scalable strategies like centrifugal and blow spinning, which are spotlighted for their efficiency and scalability in fabricating nanofiber yarns. This review further analyses recently developed nanofiber yarn applications, including wearable sensors, biomedical devices, moisture management textiles, and energy harvesting and storage devices. We finally present a forward-looking perspective to address unresolved issues in nanofiber-based yarn technologies.

Exploring the current state of technology transfer in the United States: perspectives and improvement strategies from the experts.

Technology transfer (TT) is a necessary, yet complex process to convey and disseminate scientific knowledge to the commercial sector. However, multiple barriers in TT can impede commercialization and innovative progress. To cultivate a deeper understanding, we conducted five interviews with strategic, elite leaders in different areas of TT in the United States. Experts shared their perspectives on the current state of TT, what needs improvement, and potential solutions to enhance the TT landscape, with a focus on biotechnology and medical devices. The formation of strong management teams, a comprehension of the regulatory, reimbursement, and funding pathways and policies, and thorough market assessments were noted as key aspects for venture success. Collaboration with Technology Transfer Offices (TTOs), industry experts, and strategic partners are also essential to support academic innovators and guide them throughout the complex commercialization process. There is agreement that a venture should have a defined vision and clear goals with a robust business case for the innovation; early involvement of TTOs is essential. Comprehension of the complexities and key facets of TT, while also streamlining the process, will better position biomedical innovators for success.

Computed tomography technologies to measure key structural features of polymeric biomedical implants from bench to bedside.

Implanted polymeric devices, designed to encourage tissue regeneration, require porosity. However, characterizing porosity, which affects many functional device properties, is non-trivial. Computed tomography (CT) is a quick, versatile, and non-destructive way to gain 3D structural information, yet various CT technologies, such as benchtop, preclinical and clinical systems, all have different capabilities. As system capabilities determine the structural information that can be obtained, seamless monitoring of key device features through all stages of clinical translation must be engineered intentionally. Therefore, in this study we tested feasibility of obtaining structural information in pre-clinical systems and high-resolution micro-CT (µCT) under physiological conditions. To overcome the low CT contrast of polymers in hydrated environments, radiopaque nanoparticle contrast agent was incorporated into porous devices. The size of resolved features in porous structures is highly dependent on the resolution (voxel size) of the scan. As the voxel size of the CT scan increased (lower resolution) from 5 to 50 µm, the measured pore size was overestimated, and percentage porosity was underestimated by nearly 50%. With the homogeneous introduction of nanoparticles, changes to device structure could be quantified in the hydrated state, including at high-resolution. Biopolymers had significant structural changes post-hydration, including a mean increase of 130% in pore wall thickness that could potentially impact biological response. By incorporating imaging capabilities into polymeric devices, CT can be a facile way to monitor devices from initial design stages through to clinical translation.

Design and Development of Transient Sensing Devices for Healthcare Applications.

With the ever-growing requirements in the healthcare sector aimed at personalized diagnostics and treatment, continuous and real-time monitoring of relevant parameters is gaining significant traction. In many applications, health status monitoring may be carried out by dedicated wearable or implantable sensing devices only within a defined period and followed by sensor removal without additional risks for the patient. At the same time, disposal of the increasing number of conventional portable electronic devices with short life cycles raises serious environmental concerns due to the dangerous accumulation of electronic and chemical waste. An attractive solution to address these complex and contradictory demands is offered by biodegradable sensing devices. Such devices may be able to perform required tests within a programmed period and then disappear by safe resorption in the body or harmless degradation in the environment. This work critically assesses the design and development concepts related to biodegradable and bioresorbable sensors for healthcare applications. Different aspects are comprehensively addressed, from fundamental material properties and sensing principles to application-tailored designs, fabrication techniques, and device implementations. The emerging approaches spanning the last 5 years are emphasized and a broad insight into the most important challenges and future perspectives of biodegradable sensors in healthcare are provided.

Design and validation of a low-cost photomodulator for in vivo photoactivation of a mGluR5 inhibitor.

Purpose: Severe side effects prevent the utilization of otherwise promising drugs in treatments. These side effects arise when drugs affect untargeted tissues due to poor target specificity. In photopharmacology, light controls the timing and the location of drug delivery, improving treatment specificity and pharmacokinetic control. Photopharmaceuticals have not seen widespread adoption in part because researchers do not always have access to reliable and reproducible light delivery devices at prices which fit within the larger research budget. Method: In this work, we present a customizable photomodulator for use in both wearable and implantable devices. For experimental validation of the photomodulator, we photolyse JF-NP-26 in rats. Results: We successfully drive in vivo photopharmacology with a tethered photomodulator and demonstrate modifications which enable the photomodulator to operate wirelessly. Conclusion: By documenting our photomodulator development, we hope to introduce researchers to a simple solution which significantly lowers the engineering barriers to photopharmacology research. Graphical abstract: Researchers present a photomodulator, a device designed to facilitate in vivo photopharmacology. They demonstrate the in vivo capabilities of the photomodulator by photoreleasing raseglurant, an mGluR5 inhibitor, to treat pain in an acute rat model and follow this study by showing how to reconfigure the photomodulator to work wirelessly and interface with other biomedical devices. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00334-3.

An Optical Signal Simulator for the Characterization of Photoplethysmographic Devices.

(1) Background: An optical simulator able to provide a repeatable signal with desired characteristics as an input to a photoplethysmographic (PPG) device is presented in order to compare the performance of different PPG devices and also to test the devices with PPG signals available in online databases. (2) Methods: The optical simulator consists of an electronic board containing a photodiode and LEDs at different wavelengths in order to simulate light reflected by the body; the PPG signal taken from the chosen database is reproduced by the electronic board, and the board is used to test a wearable PPG medical device in the form of earbuds. (3) Results: The PPG device response to different average and peak-to-peak signal amplitudes is shown in order to assess the device sensitivity, and the fidelity in tracking the actual heart rate is also investigated. (4) Conclusions: The developed optical simulator promises to be an affordable, flexible, and reliable solution to test PPG devices in the lab, allowing the testing of their actual performances thanks to the possibility of using PPG databases, thus gaining useful and significant information before on-the-field clinical trials.

The Use of Functional Biomaterials in Aesthetic and Functional Restoration in Orbital Surgery.

The integration of functional biomaterials in oculoplastic and orbital surgery is a pivotal area where material science and clinical practice converge. This review, encompassing primary research from 2015 to 2023, delves into the use of biomaterials in two key areas: the reconstruction of orbital floor fractures and the development of implants and prostheses for anophthalmic sockets post-eye removal. The discussion begins with an analysis of orbital floor injuries, including their pathophysiology and treatment modalities. It is noted that titanium mesh remains the gold standard for orbital floor repair due to its effectiveness. The review then examines the array of materials used for orbital implants and prostheses, highlighting the dependence on surgeon preference and experience, as there are currently no definitive guidelines. While recent innovations in biomaterials show promise, the review underscores the need for more clinical data before these new materials can be widely adopted in clinical settings. The review advocates for an interdisciplinary approach in orbital surgery, emphasizing patient-centered care and the potential of biomaterials to significantly enhance patient outcomes.

Review of Piezoelectrical Materials Potentially Useful for Peripheral Nerve Repair.

It has increasingly been recognized that electrical currents play a pivotal role in cell migration and tissue repair, in a process named "galvanotaxis". In this review, we summarize the current evidence supporting the potential benefits of electric stimulation (ES) in the physiology of peripheral nerve repair (PNR). Moreover, we discuss the potential of piezoelectric materials in this context. The use of these materials has deserved great attention, as the movement of the body or of the external environment can be used to power internally the electrical properties of devices used for providing ES or acting as sensory receptors in artificial skin (e-skin). The fact that organic materials sustain spontaneous degradation inside the body means their piezoelectric effect is limited in duration. In the case of PNR, this is not necessarily problematic, as ES is only required during the regeneration period. Arguably, piezoelectric materials have the potential to revolutionize PNR with new biomedical devices that range from scaffolds and nerve-guiding conduits to sensory or efferent components of e-skin. However, much remains to be learned regarding piezoelectric materials, their use in manufacturing of biomedical devices, and their sterilization process, to fine-tune their safe, effective, and predictable in vivo application.

Development of a Carbon Nanotube-Enhanced FAS Bilayer Amphiphobic Coating for Biological Fluids.

This study reports the development of a novel amphiphobic coating. The coating is a bilayer arrangement, where carbon nanotubes (CNTs) form the underlayer and fluorinated alkyl-silane (FAS) forms the overlayer, resulting in the development of highly amphiphobic coatings suitable for a wide range of substrates. The effectiveness of these coatings is demonstrated through enhanced contact angles for water and artificial blood plasma fluid on glass, stainless steel, and porous PTFE. The coatings were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), atomic force microscopy (AFM), and contact angle (CA) measurements. The water contact angles achieved with the bilayer coating were 106 ± 2°, 116 ± 2°, and 141 ± 2° for glass, stainless steel, and PTFE, respectively, confirming the hydrophobic nature of the coating. Additionally, the coating displayed high repellency for blood plasma, exhibiting contact angles of 102 ± 2°, 112 ± 2°, and 134 ± 2° on coated glass, stainless steel, and PTFE surfaces, respectively. The presence of the CNT underlayer improved plasma contact angles by 29%, 21.7%, and 16.5% for the respective surfaces. The presence of the CNT layer improved surface roughness significantly, and the average roughness of the bilayer coating on glass, stainless steel, and PTFE was measured to be 488 nm, 301 nm, and 274 nm, respectively. Mechanistically, the CNT underlayer contributed to the surface roughness, while the FAS layer provided high amphiphobicity. The maximum effect was observed on modified glass, followed by stainless steel and PTFE surfaces. These findings highlight the promising potential of this coating method across diverse applications, particularly in the biomedical industry, where it can help mitigate complications associated with device-fluid interactions.

A Glutaraldehyde-Free Crosslinking Method for the Treatment of Collagen-Based Biomaterials for Clinical Application.

Biological bioprostheses such as grafts, patches, and heart valves are often derived from biological tissue like the pericardium. These bioprostheses can be of xenogenic, allogeneic, or autologous origin. Irrespective of their origin, all types are pre-treated via crosslinking to render the tissue non-antigenic and mechanically strong or to minimize degradation. The most widely used crosslinking agent is glutaraldehyde. However, glutaraldehyde-treated tissue is prone to calcification, inflammatory degradation, and mechanical injury, and it is incapable of matrix regeneration, leading to structural degeneration over time. In this work, we are investigating an alternative crosslinking method for an intraoperative application. The treated tissue's crosslinking degree was evaluated by differential scanning calorimetry. To confirm the findings, a collagenase assay was conducted. Uniaxial tensile testing was used to assess the tissue's mechanical properties. To support the findings, the treated tissue was visualized using two-photon microscopy. Additionally, fourier transform infrared spectroscopy was performed to study the overall protein secondary structure. Finally, a crosslinking procedure was identified for intraoperative processing. The samples showed a significant increase in thermal and enzymatic stability after treatment compared to the control, with a difference of up to 22.2 °C and 100%, respectively. Also, the tissue showed similar biomechanics to glutaraldehyde-treated tissue, showing greater extensibility, a higher failure strain, and a lower ultimate tensile strength than the control. The significant difference in the structure band ratio after treatment is proof of the introduction of additional crosslinks compared to the untreated control with regard to differences in the amide-I region. The microscopic images support these findings, showing an alteration of the fiber orientation after treatment. For collagen-based biomaterials, such as pericardial tissue, the novel phenolic crosslinking agent proved to be an equivalent alternative to glutaraldehyde regarding tissue characteristics. Although long-term studies must be performed to investigate superiority in terms of longevity and calcification, our novel crosslinking agent can be applied in concentrations of 1.5% or 2.0% for the treatment of biomaterials.

Customised 3D-Printed Surgical Guide for Breast-Conserving Surgery after Neoadjuvant Chemotherapy and Its Clinical Application.

For patients eligible to undergo breast-conserving surgery (BCS) after neoadjuvant chemotherapy, accurate preoperative localisation of tumours is vital to ensure adequate tumour resection that can reduce recurrence probability effectively. For this reason, we have developed a 3D-printed personalised breast surgery guide (BSG) assisted with supine magnetic resonance imaging (MRI) and image 3D reconstruction technology, capable of mapping the tumour area identified on MRI onto the breast directly using dual positioning based on the manubrium and nipple. In addition, the BSG allows the colour dye to be injected into the breast to mark the tumour region to be removed, yielding more accurate intraoperative resection and satisfactory cosmetic outcomes. The device has been applied to 14 patients from January 2018 to July 2023, with two positive margins revealed by the intraoperative biopsy. This study showed that the BSG-based method could facilitate precise tumour resection of BCS by accurately localising tumour extent and margin, promoting the clinical efficacy in patients with breast cancer as well as simplifying the surgical process.

Development and Validation of a Novel In Vitro Joint Testing System for Reproduction of In Vivo Dynamic Muscle Force.

In vitro biomechanical experiments utilizing cadaveric specimens are one of the most effective methods for rehearsing surgical procedures, testing implants, and guiding postoperative rehabilitation. Applying dynamic physiological muscle force to the specimens is a challenge to reconstructing the environment of bionic mechanics in vivo, which is often ignored in the in vitro experiment. The current work aims to establish a hardware platform and numerical computation methods to reproduce dynamic muscle forces that can be applied to mechanical testing on in vitro specimens. Dynamic muscle loading is simulated through numerical computation, and the inputs of the platform will be derived. Then, the accuracy and robustness of the platform will be evaluated through actual muscle loading tests in vitro. The tests were run on three muscles (gastrocnemius lateralis, the rectus femoris, and the semitendinosus) around the knee joint and the results showed that the platform can accurately reproduce the magnitude of muscle strength (errors range from -6.2% to 1.81%) and changing pattern (goodness-of-fit range coefficient ranges from 0.00 to 0.06) of target muscle forces. The robustness of the platform is mainly manifested in that the platform can still accurately reproduce muscle force after changing the hardware combination. Additionally, the standard deviation of repeated test results is very small (standard ranges of hardware combination 1: 0.34 N~2.79 N vs. hardware combination 2: 0.68 N~2.93 N). Thus, the platform can stably and accurately reproduce muscle forces in vitro, and it has great potential to be applied in the future musculoskeletal loading system.

Novel Material Optimization Strategies for Developing Upgraded Abdominal Meshes.

Over 20 million hernias are operated on globally per year, with most interventions requiring mesh reinforcement. A wide range of such medical devices are currently available on the market, most fabricated from synthetic polymers. Yet, searching for an ideal mesh is an ongoing process, with continuous efforts directed toward developing upgraded implants by modifying existing products or creating innovative systems from scratch. In this regard, this review presents the most frequently employed polymers for mesh fabrication, outlining the market available products and their relevant characteristics, further focusing on the state-of-the-art mesh approaches. Specifically, we mainly discuss recent studies concerning coating application, nanomaterials addition, stem cell seeding, and 3D printing of custom mesh designs.