Self-Searching Writing of Human-Organ-Scale Three-Dimensional Topographic Scaffolds with Shape Memory by Silkworm-like Electrospun Autopilot Jet.

Bioengineered scaffolds satisfying both the physiological and anatomical considerations could potentially repair partially damaged tissues to whole organs. Although three-dimensional (3D) printing has become a popular approach in making 3D topographic scaffolds, electrospinning stands out from all other techniques for fabricating extracellular matrix mimicking fibrous scaffolds. However, its complex charge-influenced jet-field interactions and the associated random motion were hardly overcome for almost a century, thus preventing it from being a viable technique for 3D topographic scaffold construction. Herein, we constructed, for the first time, geometrically challenging 3D fibrous scaffolds using biodegradable poly(ε-caprolactone), mimicking human-organ-scale face, female breast, nipple, and vascular graft, with exceptional shape memory and free-standing features by a novel field self-searching process of autopilot polymer jet, essentially resembling the silkworm-like cocoon spinning. With a simple electrospinning setup and innovative writing strategies supported by simulation, we successfully overcame the intricate jet-field interactions while preserving high-fidelity template topographies, via excellent target recognition, with pattern features ranging from 100's µm to 10's cm. A 3D cell culture study ensured the anatomical compatibility of the so-made 3D scaffolds. Our approach brings the century-old electrospinning to the new list of viable 3D scaffold constructing techniques, which goes beyond applications in tissue engineering.

Single-cell RNA-Seq reveals the potential risk of anti-mesothelin CAR T Cell therapy toxicity to different organs in humans.

"On-target off-tumor" toxicity is a major challenge to the use of chimeric antigen receptor (CAR)-engineered T cells in the treatment of solid malignancies, because of the expression of target antigens in normal tissues. Mesothelin overexpression is associated with poor prognosis of multiple solid tumors, and would therefore appear to be a suitable antigen target. To understand the risk of toxicity to different organs on anti-mesothelin CAR T cell therapy, single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems were analyzed in this study, including the respiratory, cardiovascular, digestive, and urinary systems. According to scRNA-seq datasets, the organs were stratified into high or low risk based on the level of mesothelin expression. We report that the proportion of mesothelin-positive cells was 7.71%, 2.40% and 2.20% of myocardial cells, pulmonary cells and stomach cells, respectively, indicating that these organs could be at high risk of "on-target off-tumor" toxicity on anti-mesothelin CAR T cell therapy. By contrast, esophagus, ileum, liver, kidney and bladder exhibited low mesothelin expression (<1%). Therefore, these organs could be regarded as at low risk. Thus, the risk of toxicity to different organs and tissues in anti-mesothelin CAR T cell therapy may be predicted by these scRNA-seq data.

Artificial Intelligence Radiotherapy Planning: Automatic Segmentation of Human Organs in CT Images Based on a Modified Convolutional Neural Network.

Objective: Precise segmentation of human organs and anatomic structures (especially organs at risk, OARs) is the basis and prerequisite for the treatment planning of radiation therapy. In order to ensure rapid and accurate design of radiotherapy treatment planning, an automatic organ segmentation technique was investigated based on deep learning convolutional neural network. Method: A deep learning convolutional neural network (CNN) algorithm called BCDU-Net has been modified and developed further by us. Twenty two thousand CT images and the corresponding organ contours of 17 types delineated manually by experienced physicians from 329 patients were used to train and validate the algorithm. The CT images randomly selected were employed to test the modified BCDU-Net algorithm. The weight parameters of the algorithm model were acquired from the training of the convolutional neural network. Result: The average Dice similarity coefficient (DSC) of the automatic segmentation and manual segmentation of the human organs of 17 types reached 0.8376, and the best coefficient reached up to 0.9676. It took 1.5-2 s and about 1 h to automatically segment the contours of an organ in an image of the CT dataset for a patient and the 17 organs for the CT dataset with the method developed by us, respectively. Conclusion: The modified deep neural network algorithm could be used to automatically segment human organs of 17 types quickly and accurately. The accuracy and speed of the method meet the requirements of its application in radiotherapy.

Infection and utilization rates of bone allografts in a hospital-based musculoskeletal tissue bank in north India.

BACKGROUND: The bone bank unit of interest in this article was established in January 2018, in a tertiary care teaching institute of north India. Aim of this article is to describe the sources of allografts obtained, discard rates of allografts and infection rates in the recipients after use. MATERIAL AND METHODS: All the relevant details of donors and recipients were maintained, and donors were screened for standard inclusion and exclusion criteria before obtaining the grafts. Aerobic culture was performed before storage and just prior to use. Samples with incomplete documentation, incomplete donor screening or positive cultures were discarded. Data on surgical site infection in recipients was collected from hospital records retrospectively. Initially ELISA based serological tests were used for screening. Donor has to undergo these tests again after 6 months to account for the window period of proliferation of viruses. Nucleic acid amplification tests (NAAT) for these viral agents were introduced in the hospital in May 2018. RESULTS: Allografts from a total of 196 donors were obtained in the bone bank over 2 years. Major source of bone was femoral heads harvested during total hip arthroplasty or hemi-arthroplasty. 44(22.4%) grafts had to be discarded. 95 allografts were used in 88 patients during this time. Most common indication for use was surgery for bone tumors (40%), followed by complex primary or revision arthroplasty (30.5%). Three (3.4%) recipients developed deep infection postoperatively. CONCLUSION: Frozen allograft bone from hospital based bone banks is a reliable source of allografts. When meticulous precautions for sterility are followed, risk of infection is low. Monitoring of such bone banks should fall within a framework of the local legislature. Incomplete documentation is the major reason for wastage of the samples obtained. NAAT may be useful in screening of donors, as it reduces the wastage and the holding time of the allografts.

Graphene Oxide: Opportunities and Challenges in Biomedicine.

Desirable carbon allotropes such as graphene oxide (GO) have entered the field with several biomedical applications, owing to their exceptional physicochemical and biological features, including extreme strength, found to be 200 times stronger than steel; remarkable light weight; large surface-to-volume ratio; chemical stability; unparalleled thermal and electrical conductivity; and enhanced cell adhesion, proliferation, and differentiation properties. The presence of functional groups on graphene oxide (GO) enhances further interactions with other molecules. Therefore, recent studies have focused on GO-based materials (GOBMs) rather than graphene. The aim of this research was to highlight the physicochemical and biological properties of GOBMs, especially their significance to biomedical applications. The latest studies of GOBMs in biomedical applications are critically reviewed, and in vitro and preclinical studies are assessed. Furthermore, the challenges likely to be faced and prospective future potential are addressed. GOBMs, a high potential emerging material, will dominate the materials of choice in the repair and development of human organs and medical devices. There is already great interest among academics as well as in pharmaceutical and biomedical industries.

Electromagnetic pollution alert: Microwave radiation and absorption in human organs and tissues.

Electromagnetic radiation from communication and electronic devices, networks, systems and base stations has drawn concern due to excessive global usage with increasing power and operating frequency level. Numerous previous researches only focus on how the radiation from certain frequency ranges of particular devices could harm specific human organs and tissues, resulting in distinct symptoms. In this research, electromagnetic propagation and properties in 14 human organs and tissues were analyzed and investigated based on the organs and tissues' electromagnetic and mechanical parameters, and chemical composition. Counting the organs and tissues as electromagnetic materials, their permittivity and conductivity, computed by a 4-Cole-Cole mode, directly respective to the operating frequency, are interrelated to wave behavior and hence influence the organs' response. Tests were conducted in 1 GHz to 105 GHz system settings, covering most microwave frequency uses: 2.4 GHz of 4G-LTE, Wi-Fi, Bluetooth, ZigBee and the 5G ranges: 28 GHz of 5G-mmW and 95 GHz of 5G-IoT. Trial human organs and tissues were placed in the wave propagation direction of 2.4 GHz and 28 GHz dipole antennas, and a waveguide port operating from 95 to 105 GHz. The quantitative data on the effects of 5G penetration and dissipation within human tissues are presented. The absorbance in all organs and tissues is significantly higher as frequency increases. As the wave enters the organ-tissue model, the wavelength is shortened due to the high organ-tissue permittivity. Skin-Bone-Brain layer simulation results demonstrate that both electric and magnetic fields vanish before passing the brain layer at all three focal frequencies of 2.4 GHz, 28 GHz and 100 GHz.

Plasma-Rich in Growth Factor and its Clinical Application.

The potential use of growth factors in stem cell-based therapies for the repair and regeneration of tissues and organs offers a paradigm shift in regenerative medicine. Growth factors are critical signalling molecules that play an important role in tissue development and remodelling. Plasma rich in growth factor (PRGF) is a biotechnological strategy for the harvesting of the active substances of platelets, including growth factors, from the patient's blood. Because of their tremendous essential growth factor and bioactive agents, as well as their paracrine mechanisms, PRGF has been used as an efficacious option and adjuvant biological therapy in the repair and replacement of damaged organs. This article provides an overview of PRGF extraction and its properties and critically reviewed its clinical benefit and clinical trials in the treatment and regeneration of human organs. Regenerative medicine is a multi-billion-dollar industry with huge interest to clinicians, academics and industries, being considered as an emerging technology.

Nickel Content in Human Internal Organs.

With the growing interest in new applications of metals in modern technologies, an increase in their concentration in the environment can be observed, which, in consequence, may constitute a hazard to human health. That is why it is of a great importance to establish "reference" levels of particular elements (essential or toxic) in human biological samples.The aim of this paper was to determine nickel in autopsy tissues of non-occupationally exposed subjects in Southern Poland (n = 60). Measurements were performed by means of electrothermal atomic absorption spectrometry after microwave-assisted acid digestion according to previously optimized and validated procedure. The results obtained indicate that data cover the wide range of concentrations and generally are consistent with other published findings. Nickel levels in the brain, stomach, liver, kidneys, lungs and heart (wet weight) were between 2.15-79.4 ng/g, 0.5-44.2 ng/g,7.85-519 ng/g, 12.8-725 ng/g, 8.47-333 ng/g and 2.3-97.7 ng/g, respectively. Females had generally lower levels of nickel in tissues than males (statistically significant relationships were found for the liver, kidneys and lungs), and median nickel concentrations in all studied material within all age groups had very similar values, with the exception of stomach.

Investigation of absorption, metabolism and toxicity of ginsenosides compound K based on human organ chips.

Organ-on-a-chip as a new technology distinguishes it from animal and cell models at least in three aspects: (1) it responds to drugs' efficacy or toxicity more really by mimicking the human body's fluid microenvironment; (2) it can be used for high throughput screening a large number of compounds; (3) it has physiological accuracy. It is well known that ginsenosides compound K (CK) as a carbohydrate drug has numerous biological activities and physiological functions. However, pharmacokinetic studies of carbohydrate-based CK haven't been performed on organ chips. Here, we established and evaluated the function of single-organ chips and multi-organ chips based on intestinal, vascular, liver, and kidney chips. Each single-organ-on-a-chip performed itself well. Based on organ-on-chips, absorption, metabolism and toxicity of CK were successfully investigated. The pharmacokinetic results of CK provided by chip were consistent with previous reports, demonstrating the reliability of the organ-on-a-chip platform and its potential for use in pharmacokinetic studies of carbohydrate-drugs. As far as we know, this study would be the first report on the pharmacological investigation of carbohydrate drugs on organ-on-a-chip, which provides a theoretical basis for carbohydrate-based drug discovery.

Organ-on-a-chip: recent breakthroughs and future prospects.

The organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.

Dual stir bar sorptive extraction coupled to thermal desorption-gas chromatography-mass spectrometry for the determination of endocrine disruptors in human tissues.

The validation of a procedure for the determination of six alkylphenols (APs), 4-tert-butylphenol, 4-pentylphenol, 4-tert-octylphenol, 4-hexylphenol, 4-octylphenol and 4-nonylphenol, and three bisphenols (BPs), bisphenol A, bisphenol F and bisphenol Z, in seven human organs and tissues (kidney, liver, heart, lung, spleen, brain and abdominal fat) obtained from eight autopsies is presented. Previously ground samples were treated by salt-assisted liquid-liquid extraction (SALLE) for isolation of the analytes and then pre-concentrated using dual stir bar sorptive extraction (SBSE), allowing two different extraction conditions for the same sample. Finally, thermal desorption was used as the injector system in combination with gas chromatography coupled to mass spectrometry (GC-MS). To determine BPs, derivatization using acetic anhydride was required, although this step was not necessary for the APs. Two parallel extractions of the contaminants with the stir bars were performed, followed by thermal desorption and chromatographic analysis. The procedure provided quantification limits between 0.050 and 4.0 ng g-1 for APs and from 0.26 to 2.6 ng g-1 for BPs. Repeatability and reproducibility values were lower than 15% in all cases. The accuracy of the procedure was established by a recovery study, which provided values in the 85.8-115% range for APs and 83.6-120% for BPs. Samples were analyzed with the proposed methodology and data were processed by ANOVA tests to study the behaviour and bioaccumulation of these compounds in human tissues or organs. In addition, discriminant analysis detected age- and sex-dependent differences in bioaccumulation.

Three-dimensional Printing in Anatomy Education: Assessing Potential Ethical Dimensions.

New technological developments have frequently had major consequences for anatomy education, and have raised ethical queries for anatomy educators. The advent of three-dimensional (3D) printing of human material is showing considerable promise as an educational tool that fits alongside cadaveric dissection, plastination, computer simulation, and anatomical models and images. At first glance its ethical implications appear minimal, and yet the more extensive ethical implications around clinical bioprinting suggest that a cautious approach to 3D printing in the dissecting room is in order. Following an overview of early groundbreaking studies into 3D printing of prosections, organs, and archived fetal material, it has become clear that their origin, using donated bodies or 3D files available on the Internet, has ethical overtones. The dynamic presented by digital technology raises questions about the nature of the consent provided by the body donor, reasons for 3D printing, the extent to which it will be commercialized, and its comparative advantages over other available teaching resources. In exploring questions like these, the place of 3D printing within a hierarchical sequence of value is outlined. Discussion centers on the significance of local usage of prints, the challenges created by regarding 3D prints as disposable property, the importance of retaining the human side to anatomy, and the unacceptability of obtaining 3D-printed material from unclaimed bodies. It is concluded that the scientific tenor of 3D processes represents a move away from the human person, so that efforts are required to prevent them accentuating depersonalization and commodification.

Regulatory aspects of tissue donation, banking and transplantation in India.

Amendments to India's Transplantation of Human Organs Act, 1994, have established the legality of tissue donation and transplantation from deceased donors and the conditions under which they are permitted. The amended Act, now known as The Transplantation of Human Organs and Tissues Act, 1994, seeks to prevent the commercialization of tissue donation and to guarantee the safety of indigenous allografts. Registration of tissue banks, compliance with national standards and the appointment of transplant co-ordinators in hospitals registered under the Act are now mandatory. A national registry and Regional and State networks for donation and transplantation of tissues have been introduced. Despite the amendments a few anomalies of the principal Act persist as some of the differences between tissue and organ donation and transplantation have been overlooked. These include the possibility of skin donation in locations other than hospitals; the donation of medical and surgical tissue residues which does not pose any risk to the living donor; the non-requirement for compatibility between donor and recipient; the delayed time factor between tissue donation and transplantation which makes identification of a recipient at the time of donation impossible; and the easy availability of alternatives to tissues which make waiting lists redundant for many tissues. Rules for the implementation of the amended Act were framed in 2014 but like the Act must be adopted by the State health assemblies to become universally applicable in the country.

Chromium in Postmortem Material.

Recently, considerable attention has been paid to the negative effects caused by the presence and constant increase in concentration of heavy metals in the environment, as well as to the determination of their content in human biological samples. In this paper, the concentration of chromium in samples of blood and internal organs collected at autopsy from 21 female and 39 male non-occupationally exposed subjects is presented. Elemental analysis was carried out by an electrothermal atomic absorption spectrometer after microwave-assisted acid digestion. Reference ranges of chromium in the blood, brain, stomach, liver, kidneys, lungs, and heart (wet weight) in the population of Southern Poland were found to be 0.11-16.4 ng/mL, 4.7-136 ng/g, 6.1-76.4 ng/g, 11-506 ng/g, 2.9-298 ng/g, 13-798 ng/g, and 3.6-320 ng/g, respectively.

3D Miniaturization of Human Organs for Drug Discovery.

"Engineered human organs" hold promises for predicting the effectiveness and accuracy of drug responses while reducing cost, time, and failure rates in clinical trials. Multiorgan human models utilize many aspects of currently available technologies including self-organized spherical 3D human organoids, microfabricated 3D human organ chips, and 3D bioprinted human organ constructs to mimic key structural and functional properties of human organs. They enable precise control of multicellular activities, extracellular matrix (ECM) compositions, spatial distributions of cells, architectural organizations of ECM, and environmental cues. Thus, engineered human organs can provide the microstructures and biological functions of target organs and advantageously substitute multiscaled drug-testing platforms including the current in vitro molecular assays, cell platforms, and in vivo models. This review provides an overview of advanced innovative designs based on the three main technologies used for organ construction leading to single and multiorgan systems useable for drug development. Current technological challenges and future perspectives are also discussed.

Sensor-free and Sensor-based Heart-on-a-chip Platform: A Review of Design and Applications.

Drug efficacy and toxicity are key factors of drug development. Conventional 2D cell models or animal models have their limitations for the efficacy or toxicity assessment in preclinical assays, which induce the failure of candidate drugs or withdrawal of approved drugs. Human organs-on-chips (OOCs) emerged to present human-specific properties based on their 3D bioinspired structures and functions in the recent decade. In this review, the basic definition and superiority of OOCs will be introduced. Moreover, a specific OOC, heart-on-achip (HOC) will be focused. We introduce HOC modeling in the sensor-free and sensor-based way and illustrate the advantages of sensor-based HOC in detail by taking examples of recent studies. We provide a new perspective on the integration of HOC technology and biosensing to develop a new sensor-based HOC platform.

Organ Vouchers and Barter Markets: Saving Lives, Reducing Suffering, and Trading in Human Organs.

The essays in this issue of The Journal of Medicine and Philosophy explore an innovative voucher program for encouraging kidney donation. Discussions cluster around a number of central moral and political/theoretical themes: (1) What are the direct and indirect health care costs and benefits of such a voucher system in human organs? (2) Do vouchers lead to more effective and efficient organ procurement and allocation or contribute to greater inequalities and inefficiencies in the transplantation system? (3) Do vouchers contribute to the inappropriate commodification of human body parts? (4) Is there a significant moral difference between such a voucher system and a market in human organs for transplantation? This paper argues that while kidney vouchers constitute a step in the right direction, fuller utilization of market-based incentives, including, but not limited to, barter exchanges (e.g., organ exchanges, organ chains, and organ vouchers), would save more lives and further reduce human suffering.

The five elements of the cell.

Everything in the surrounding universe can be attributed into five elements. Human organs can be also linked to the five elements. Cells, the smallest unit of the human body, consist of cellular organelles as little organs. Here, we extended the concept of the five elements to a cellular level via the human organs, theoretically re-evaluating the overall association of cellular organelles in maintaining the homeostasis of cellular functions.

Human-animal chimeras: ethical issues about farming chimeric animals bearing human organs.

Recent advances in stem cells and gene engineering have paved the way for the generation of interspecies chimeras, such as animals bearing an organ from another species. The production of a rat pancreas by a mouse has demonstrated the feasibility of this approach. The next step will be the generation of larger chimeric animals, such as pigs bearing human organs. Because of the dramatic organ shortage for transplantation, the medical needs for such a transgressive practice are indisputable. However, there are serious technical barriers and complex ethical issues that must be discussed and solved before producing human organs in animals. The main ethical issues are the risks of consciousness and of human features in the chimeric animal due to a too high contribution of human cells to the brain, in the first case, or for instance to limbs, in the second. Another critical point concerns the production of human gametes by such chimeric animals. These worst-case scenarios are obviously unacceptable and must be strictly monitored by careful risk assessment, and, if necessary, technically prevented. The public must be associated with this ethical debate. Scientists and physicians have a critical role in explaining the medical needs, the advantages and limits of this potential medical procedure, and the ethical boundaries that must not be trespassed. If these prerequisites are met, acceptance of such a new, borderline medical procedure may prevail, as happened before for in-vitro fertilization or preimplantation genetic diagnosis.

Liver Transplantation in India: At the Crossroads.

As the liver transplant journey in India reaches substantial numbers and suggests quality technical expertise, it is time to dispassionately look at the big picture, identify problems, and consider corrective measures for the future. Several features characterize the current scenario. Although the proportion of deceased donor liver transplants is increasing, besides major regional imbalances, the activity is heavily loaded in favor of the private sector and live donor transplants. The high costs of the procedure, the poor participation of public hospitals, the lack of a national registry, and outcomes reporting are issues of concern. Organ sharing protocols currently based on chronology or institutional rotation need to move to a more justiciable severity-based system. Several measures can expand the deceased donor pool. The safety of the living donor continues to need close scrutiny and focus. Multiple medical challenges unique to the Indian situation are also being thrown up. Although many of the deficits demand state intervention and policy changes the transplant community needs to take notice and highlight them. The future of liver transplantation in India should move toward a more accountable, equitable, and accessible form. We owe this to our citizens who have shown tremendous faith in us by volunteering to be living donors as well as consenting for deceased donation.