Frontiers in Medical Technology最新文献

Background: Medical device manufacturers are obliged to prove the biocompatibility of their products when they come into contact with the human body. The requirements for the biological evaluation of medical devices are specified by the international standard series ISO 10993. Part five of this series describes the performance of in vitro cytotoxicity tests. This test evaluates the effects of medical device use on cell health. The existence of the specific standard suggests that the tests will produce reliable and comparable results. However, the ISO 10993-5 offers wide latitude in the test specifications. In the past, we noticed inconsistencies of the results from different laboratories.

Objective: To determine if the specifications of the standard ISO 10993-5 are explicit to ensure the comparability of test results and, if not, identify potential influencing factors.

Methods: An interlaboratory comparison was conducted for the in vitro cytotoxicity test according to ISO 10993-5. Fifty-two international laboratories evaluated the cytotoxicity for two unknown samples. One was polyethylene (PE) tubing, which is expected to be non-cytotoxic and the other was polyvinyl chloride (PVC) tubing, for which a cytotoxic potential was presumed. All laboratories were asked to perform an elution test with predefined extraction specifications. The other test parameters were freely chosen by the laboratories according to the guidelines set by the standard.

Results: To our surprise only 58 percent of the participating laboratories identified the cytotoxic potential of both materials as expected. Particularly for PVC a considerable variation of the results between the laboratories was observed [mean = 43 ± 30 (SD), min = 0, max = 100]. We showed that ten percent serum supplementation to the extraction medium, as well as longer incubation of the cells with the extract, greatly increased the test sensitivity for PVC.

Conclusion: The results clearly show that the specifications set by the ISO 10993-5 are not explicit enough to obtain comparable results for an identical medical device. To set requirements that ensure reliable cytotoxicity assessments, further research will be necessary to identify the best test conditions for specific materials and/or devices and the standard needs to be revised accordingly.

Introduction: Wound healing consists of a dynamic series of events that are highly dependent on paracrine factors for proper progression through the phases of wound healing. Inappropriate progression through the phases is associated with insufficient epidermal regeneration (i.e., re-epithelialization) of wounds and subsequent propagation of chronic wounds, such as diabetic ulcers, which are associated with increased patient morbidity. Recently, investigation into the dynamic secretome of Adipose-derived Mesenchymal Stem Cells (ASCs), have shown promise in augmenting the wound healing response of chronic diabetic wounds. However, currently utilized 2D culture techniques are known to drastically alter the regenerative phenotype of ASCs. In this study a novel tissue-mimetic 3D system was utilized as a means to culture ASCs.

Methods: The capacity for the ASC secretome to augment epidermal regeneration activity was then evaluated after exposure of ASCs to "wound priming stimuli" in 2D and 3D. The priming stimuli consisted of coating the 2D and 3D systems with the wound matrix proteins, collagen type I, fibronectin, and fibrin. To understand the potential benefit of the ASC secretome in the context of diabetic wounds, keratinocytes (KCs) were exposed to super-physiological glucose levels to induce a diabetic-like phenotype (idKCs).

Results: Relative to KCs, idKC exhibited a 52% and 23% decline in proliferation and migration, respectively. Subsequently, analyses of the ASC secretome were performed. ASC conditioned media (ASC-CM) from tissue-mimetic culture demonstrated a > 50% increase secretion of proteins and a 2-fold increase in secreted EVs, relative to 2D culture. Interestingly, the different priming stimuli did not alter the total amount of protein or EVs secreted within the tissue-mimetic system. However, evaluation of specific soluble proteins via ELISA revealed significant differences in key epidermal regeneration factors, such as EGF, IGF-1, FGF-2, MMP-1, TIMP-1, and TGFβ-1. Additionally, the relative effect of ASC-EVs from the 2D and 3D system on idKCs epidermal regeneration functionality varied significantly, with EVs from 3D-Collagen culture providing the most significant benefit on idKC activity.

Discussion: Together, these data support the utilization of tissue-mimetic culture system to enhance the adaptability and secretory activity of MSC-like populations in order to generate tailored biologics, via priming stimuli, for specific wound healing applications.

As an approach to maintain patency in femoropopliteal stenting, a helical stent configuration was proposed, which showed improved patency in clinical trials. However, the effects of helical stent placement on the flow have not been quantitatively analyzed. The purpose of this study was to estimate flow velocities to quantify the influence of helical stent placement. Helical and straight stents were implanted in three healthy pigs, and the flow velocities were estimated using the time-intensity curve (TIC) in the angiography images. The angiographic images indicated thinning of the leading edge of the contrast medium through the helically deformed artery, which was not observed in the straight stent. The slower rise of the TIC peak in the helical stent indicated faster travel of this thinner edge. Arterial expansion due to stenting was observed in all cases, and the expansion rate varied according to location. All cases of helical stent implantation showed that velocity was maintained (55.0%-71.3% velocity retention), unlike for straight stent implantation (43.0%-68.0% velocity retention); however, no significant difference was observed.

Background: Laboratory dissections are essential to acquire practical skills to perform neurosurgical procedures. Despite being traditionally done on cadavers, they are often unavailable and suffer from cultural barriers in the African context. Non-cadaveric UpSurgeOn neurosurgery models have been developed to bridge this barrier, providing an almost similar experience with the human body. This study aimed to assess the impact of the UpSurgeOn hands-on-touch non-cadaver model training amongst selected Cameroon medical students.

Methods: An anonymous 35-item questionnaire was distributed online using Google drive systems to medical students who attended UpSurgeOn's hands-on-touch non-cadaver model training course. These questions aimed to capture data on previous experience with neuroanatomy and neurosurgery practicals and the perception, attitudes, and impact of the UpSurgeOn neurosurgery tool.

Results: Eighty-six students completed the survey. The mean age was 21.2 ± 1.868 years, 61.6% were males with 62.8% of respondents being medical students in preclinical years. Before the training, 29.4% had a fair knowledge of neuroanatomy. Textbooks and Youtube videos were the main sources of neuroanatomy and neurosurgery knowledge for more than half of the respondents. Up to 91.5% had no prior exposure to a neuroanatomy/neurosurgery cadaver laboratory dissection, and 22.6% and 17.6% had witnessed and performed at least one craniotomy before, respectively. There were 11.1%, 15.5%, and 31.3% of our respondents who had used a surgical microscope, a neurosurgical instrument, and the UpSurgeOn Neurosurgery tool before, respectively. The majority perceived the UpSurgeOn tool easy to use and felt they needed to learn just a few things before getting going with the box. Most thought of increasing the use of the UpSurgeOn Box and saw the need to be part of the training curriculum. Finally, the majority felt this tool helped to increase familiarity and acquire neurosurgical skills, and to develop the orientation skills needed during neurosurgical approaches.

Conclusion: Undergraduate exposure to traditional neurosurgery/neuroanatomy labs is limited in Cameroon. Neurosurgery/neuroanatomy practical skills are gained essentially using non-practical means. Most students found the UpSurgeOn tool user-friendly, saw the need to incorporate it as part of their training, and perceived it to be essential in getting acquainted with neurosurgical skills.

This case report discusses an elderly male patient (86 years old), suffering from limb pain related to ulcers in the lower limbs resulting from peripheral arterial disease (PAD). Clinically evaluated with the aid of infrared thermal imaging before, during and after treatment, he was submitted to treatment with neuromodulation protocols with REAC Technology, Neuro Postural Optimization (NPO) and Neuropsychophysical Optimization (NPPO) in association with traditional treatments for PAD. It was followed clinically with the aid of infrared thermal imaging of the lower limbs before, during and after treatment. He had a clinical result with a significant reduction in pain and infrared thermal images with complete revascularization of both feet. Evidencing that the treatment of dysfunctional adaptive responses by managing psychological factors often associated with anxiety, depression and stress performed by the REAC NPO and NPPO protocols can be a useful intervention to improve symptoms of patients with lower limb pain and circulatory disturbances.

Objective: A medical device must undergo rigorous regulatory processes to verify its safety and effectiveness while in use. In low-and middle-income countries like Uganda however, medical device innovators and designers face challenges around bringing a device from ideation to being market-ready. This is mainly attributed to a lack of clear regulatory procedures among other factors. In this paper, we illustrate the current landscape of investigational medical devices regulation in Uganda.

Methods: Information about the different bodies involved in regulation of medical devices in Uganda was obtained online. Nine medical device teams whose devices have gone through the Ugandan regulatory system were interviewed to gain insights into their experiences with the regulatory system. Interviews focused on the challenges they faced, how they navigated them, and factors that supported their progress towards putting their devices on the market.

Results: We identified different bodies that are part of the stepwise regulatory pathway of investigational medical devices in Uganda and roles played by each in the regulatory process. Experiences of the medical device teams collected showed that navigation through the regulatory system was different for each team and progress towards market readiness was fuelled by funding, simplicity of device, and mentorship.

Conclusion: Medical devices regulation exists in Uganda but is characterised by a landscape that is still in development which thereby affects the progress of investigational medical devices.

In silico medicine describes the application of computational modelling and simulation (CM&S) to the study, diagnosis, treatment or prevention of a disease. Tremendous research advances have been achieved to facilitate the use of CM&S in clinical applications. Nevertheless, the uptake of CM&S in clinical practice is not always timely and accurately reflected in the literature. A clear view on the current awareness, actual usage and opinions from the clinicians is needed to identify barriers and opportunities for the future of in silico medicine. The aim of this study was capturing the state of CM&S in clinics by means of a survey toward the clinical community. Responses were collected online using the Virtual Physiological Human institute communication channels, engagement with clinical societies, hospitals and individual contacts, between 2020 and 2021. Statistical analyses were done with R. Participants (n = 163) responded from all over the world. Clinicians were mostly aged between 35 and 64 years-old, with heterogeneous levels of experience and areas of expertise (i.e., 48% cardiology, 13% musculoskeletal, 8% general surgery, 5% paediatrics). The CM&S terms "Personalised medicine" and "Patient-specific modelling" were the most well-known within the respondents. "In silico clinical trials" and "Digital Twin" were the least known. The familiarity with different methods depended on the medical specialty. CM&S was used in clinics mostly to plan interventions. To date, the usage frequency is still scarce. A well-recognized benefit associated to CM&S is the increased trust in planning procedures. Overall, the recorded level of trust for CM&S is high and not proportional to awareness level. The main barriers appear to be access to computing resources, perception that CM&S is slow. Importantly, clinicians see a role for CM&S expertise in their team in the future. This survey offers a snapshot of the current situation of CM&S in clinics. Although the sample size and representativity could be increased, the results provide the community with actionable data to build a responsible strategy for accelerating a positive uptake of in silico medicine. New iterations and follow-up activities will track the evolution of responses over time and contribute to strengthen the engagement with the medical community.

Previously developed spatially-selective Vagus Nerve Stimulation (sVNS) allows the targeting of specific nerve fascicles through current steering in a multi-electrode nerve cuff but relies on a trial-and-error strategy to identify the relative orientation between electrodes and fascicles. Fast Neural Electrical Impedance Tomography (FN-EIT) has been recently used for imaging neural traffic in the vagus nerves of pigs in a cross-correlation study with sVNS and MicroCT fascicle tracking. FN-EIT has the potential for allowing targeted sVNS; however, up to now, stimulation and imaging have been performed with separate electrode arrays. In this study, different options were evaluated in-silico to integrate EIT and stimulation into a single electrode array without affecting spatial selectivity. The original pig vagus EIT electrode array geometry was compared with a geometry integrating sVNS and EIT electrodes, and with direct use of sVNS electrodes for EIT imaging. Modelling results indicated that both new designs could achieve image quality similar to the original electrode geometry in all tested markers (e.g., co-localisation error <100 µm). The sVNS array was considered to be the simplest due to the lower number of electrodes. Experimental results from testing evoked EIT imaging of recurrent laryngeal activity using electrodes from the sVNS cuff returned a signal-to-noise ratio similar to our previous study (3.9 ± 2.4 vs. 4.1 ± 1.5, N = 4 nerves from 3 pigs) and a lower co-localisation error (≈14% nerve diameter vs. ≈25%, N = 2 nerves from 2 pigs). Performing FN-EIT and sVNS on the same nerve cuff will facilitate translation to humans, simplify surgery and enable targeted neuromodulation strategies.