An anatomically-realistic computational framework for evaluating the efficacy of protective plates in mitigating non-penetrating ballistic impacts.

BACKGROUND: A major threat in combat scenarios is the 'behind armor blunt trauma' (BABT) of a non-penetrating ballistic impact with a ballistic protective plate (BPP). This impact results in pressure waves that propagate through tissues, potentially causing life-threatening damage. To date, there is no standardized procedure for rapid virtual testing of the effectiveness of BPP designs. The objective of this study was to develop a novel, anatomically-accurate, finite element modeling framework, as a decision-making tool to evaluate and rate the biomechanical efficacy of BPPs in protecting the torso from battlefield-acquired non-penetrating impacts. METHODS: To simulate a blunt impact with a BPP, two types of BPPs representing generic designs of threat-level III and IV plates, and a generic 5.56 mm bullet were modeled, based on their real dimensions, physical and mechanical characteristics (plate level-III is smaller, thinner, and lighter than plate level-IV). The model was validated by phantom testing. RESULTS: Plate level-IV induced greater strains and stresses in the superficial tissues post the ballistic impact, due to the fact that it is larger, thicker and heavier than plate level-III; the shock wave which is transferred to the superficial tissues behind the BPP is greater in the case of a non-penetrating impact. For example - the area under volumetric tissue exposure histograms of strains and stresses for the skin and adipose tissues were 16.6-19.2% and 17.3-20.3% greater in the case of plate level-IV, for strains and stresses, respectively. The validation demonstrates a strong agreement between the physical phantom experiment and the simulation, with only a 6.37% difference between them. CONCLUSIONS: Our modelling provides a versatile, powerful testing framework for both industry and clients of BPPs at the prototype design phase, or for quantitative standardized evaluations of candidate products in purchasing decisions and bids.

The biomechanical efficacy of a dressing with a soft cellulose fluff core in protecting prone surgical patients from chest injuries on the operating table.

Pressure ulcers are soft-tissue damage associated with tissue exposure to sustained deformations and stress concentrations. In patients who are proned for ventilation or surgery, such damage may occur in the superficial chest tissues that are compressed between the rib cage and the support surface. Prophylactic dressings have been previously proven as generally effective for pressure ulcer prevention. In this study, our goal was to develop a novel computational modelling framework to investigate the biomechanical efficacy of a dressing with a soft cellulose fluff core in protecting proned surgical patients from chest pressure ulcers occurring on the operating table, due to body fixation by the Relton-Hall frame. We compared the levels of mechanical compressive stresses developing in the soft chest tissues, above the sternum and ribs, due to the trunk weight, whilst the body is supported by the Relton-Hall frame pads, with versus without the prophylactically applied bilateral dressings. The protective efficacy index for the extremely high stresses, above the 95th-percentile, were 40.5%, 25.6% and 24.2% for skin, adipose and muscle, respectively, indicating that the dressings dispersed elevated soft-tissue stresses. The current results provide additional support for using soft cellulose fluff core dressings for pressure ulcer prophylaxis, including during surgery.

A machine learning algorithm for early detection of heel deep tissue injuries based on a daily history of sub-epidermal moisture measurements.

Sub-epidermal moisture is an established biophysical marker of pressure ulcer formation based on biocapacitance changes in affected soft tissues, which has been shown to facilitate early detection of these injuries. Artificial intelligence shows great promise in wound prevention and care, including in automated analyses of quantitative measures of tissue health such as sub-epidermal moisture readings acquired over time for effective, patient-specific, and anatomical-site-specific pressure ulcer prophylaxis. Here, we developed a novel machine learning algorithm for early detection of heel deep tissue injuries, which was trained using a database comprising six consecutive daily sub-epidermal moisture measurements recorded from 173 patients in acute and post-acute care settings. This algorithm was able to achieve strong predictive power in forecasting heel deep tissue injury events the next day, with sensitivity and specificity of 77% and 80%, respectively, revealing the clinical potential of artificial intelligence-powered technology for hospital-acquired pressure ulcer prevention. The current work forms the scientific basis for clinical implementation of machine learning algorithms that provide effective, early, and anatomy-specific preventive interventions to minimise the occurrence of hospital-acquired pressure ulcers based on routine tissue health status measurements.

Computational studies of the biomechanical efficacy of a minimum tissue deformation mattress in protecting from sacral pressure ulcers in a supine position.

Sustained soft tissue exposure to localised deformations is a trigger for the formation of pressure ulcers. Immersion and envelopment are critical benchmarks that determine comfort and the pressure ulcer risk mitigation, as they have considerable influence on tissue stress concentrations near bony prominences. In the present study, we developed a computer modelling framework for quantifying the extent by which optimal envelopment disperses tissue stress concentrations near the sacrum. To compare the risk of developing a sacral pressure ulcer while lying supine on a regular foam mattress with respect to lying on a specialised, minimum tissue deformation mattress (which closely conforms to the body contours), we used a three-dimensional anatomically-realistic model of the adult female buttocks. The strains and stresses in the subdermal soft tissues reached peak values of 65% and 2.4 kPa for the regular mattress, respectively, but always remained below 45% and 1.2 kPa for the minimum tissue deformation mattress, which indicates longer safe times for supine support on the latter mattress. Our work demonstrates that alleviation of localised, sustained stress concentrations through good immersion and envelopment of the support surface protects from pressure ulcers, and has the potential to relieve chronic pain which is associated with the pressure ulcer risk.

Biomechanical stimulation effects on the metabolism of adipocyte.

Adipose tissue plays a leading role in obesity, which, in turn, can lead to Type 2 diabetes. Adipocytes (AD) respond to the biomechanical stimulation experienced in fat tissue under static stretch during prolonged sitting or lying. To investigate the effect of such chronic stimulation on adipocyte cell metabolism, we used an in vitro system to mimic the static stretch conditions. Under in vitro culture stretching, cells were analyzed at the single-cell level and we measured an increase in the projected area of the AD and higher content of lipid droplets. A decrease in the projected area of these cells' nucleus is associated with peroxisome proliferator-activated receptor-gamma expression and heterochromatin. This is the first study to reveal proteins that were altered under static stretch following a mass spectrometry analysis and main pathways that affect cell fate and metabolism. Bioinformatics analysis of the proteins indicated an increase in mitochondrial activity and associated pathways under static stretch stimulation. Quantification of the mitochondrial activity by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and the ATPase related proteins specifically measured ATP5B indicated an increase in adipogenesis which points to a higher rate of cell metabolism under static stretch. In summary, our results elaborate on the metabolism of AD exposed to biomechanical stimulation, that is, associated with altered cellular protein profile and thereby influenced cell fate. The static stretch stimulation accelerated adipocyte differentiation through increased mitochondrial activity. Hence, in this study, we introduce a new perspective in understanding the molecular regulation of mechano-transduction in adipogenesis.

How patient migration in bed affects the sacral soft tissue loading and thereby the risk for a hospital-acquired pressure injury.

Head-of-bed (HOB) elevation is a common clinical practice in hospitals causing the patient's body to slide down in bed because of gravity. This migration effect likely results in tissue shearing between the sacrum and the support surface, which increases the risk for pressure injuries. StayInPlace (HillRom Inc.) is a commercial migration-reduction technology (MRT) incorporated in intensive care bedframes. Yet, the effects of migration-reduction on tissue shear stresses during HOB elevation are unknown. We analysed relationships between migration and resulting sacral soft tissue stresses by combining motion analysis and three-dimensional finite element modelling of the buttocks. Migration data were collected for 10 subjects, lying supine on two bedframe types with and without MRT, and at HOB elevations of 45°/65°. Migration data were used as displacement boundary conditions for the modelling to calculate tissue stress exposures. Migration values for the conventional bed were 1.75- and 1.6-times greater than those for the migration-reduction bed, for elevations of 45° and 65°, respectively (P < .001). The modelling showed that the farther the migration, the greater the tissue stress exposures. Internal stresses were 1.8-fold greater than respective skin stresses. Our results, based on the novel integrated experimental-computational method, point to clear biomechanical benefits in minimising migration using MRT.

Adipocytes Migration is Altered Through Differentiation.

Adipogenesis is a developmental process in which an elongated preadipocyte differentiates to a round adipocyte along with the accumulation of lipid droplets. In the present study, we focus on the study of cell motility at the single-cell level, toward expanding our knowledge regarding the cytoskeleton alteration during differentiation; since-cell motility is mediated by cytoskeletal components. We used the holographic-microscopy live imaging technique to evaluate, for the first time in the literature, differences between the motility of nondifferentiated preadipocytes and differentiated mature adipocytes in living cell cultures over time. We revealed that mean motility speed of preadipocytes was significantly higher (fourfold) than that of adipocytes, and that the movement of preadipocytes is less consistent and more extensive. Furthermore, we found that preadipocytes tend to migrate to farther distances, while mature adipocytes remain relatively close to their original location. The results presented here are in agreement with the fact that the cytoskeleton of adipocytes is altered during differentiation and similarly, points to the fact that the cell-sensing mechanisms are changing during differentiation. Our research paves the way to gain better insights of the differentiation process and its implications on larger scale systems in the context of obesity.

Noninvasive Continuous Monitoring of Adipocyte Differentiation: From Macro to Micro Scales.

3T3-L1 cells serve as model systems for studying adipogenesis and research of adipose tissue-related diseases, e.g. obesity and diabetes. Here, we present two novel and complementary nondestructive methods for adipogenesis analysis of living cells which facilitate continuous monitoring of the same culture over extended periods of time, and are applied in parallel at the macro- and micro-scales. At the macro-scale, we developed visual differences mapping (VDM), a novel method which allows to determine level of adipogenesis (LOA)-a numerical index which quantitatively describes the extent of differentiation in the whole culture, and percentage area populated by adipocytes (PAPBA) across a whole culture, based on the apparent morphological differences between preadipocytes and adipocytes. At the micro-scale, we developed an improved version of our previously published image-processing algorithm, which now provides data regarding single-cell morphology and lipid contents. Both methods were applied here synergistically for measuring differentiation levels in cultures over multiple weeks. VDM revealed that the mean LOA value reached 1.11 ± 0.06 and the mean PAPBA value reached >60%. Micro-scale analysis revealed that during differentiation, the cells transformed from a fibroblast-like shape to a circular shape with a build-up of lipid droplets. We predict a vast potential for implementation of these methods in adipose-related pharmacological research, such as in metabolic-syndrome studies.

Cell shape alteration during adipogenesis is associated with coordinated matrix cues.

Obesity has become one of the leading pathophysiologic disorders in recent years. Adipose tissue is the main tissue related to obesity and is known to play a role in various physiological complications, including type 2 diabetes. To better understand how the fat tissue develops, we used an in vitro live cell imaging system to quantify the adipogenesis by means of nondestructive digital imaging to monitor the accumulation of intracellular lipid droplets (LDs), a hallmark of adipogenesis, from the macro- to the micro-scale. Analyzing the cells' shape at the single-cell level allows to quantify the cells' shape change from a fibroblast to spherical morphology, indicating the start of adipogenesis. To reveal the molecular alterations, we applied a proteomic approach using high-resolution mass spectrometry of the proliferation, confluent fibroblasts and of adipocytes. During this process, we noted the reorganization of the cells' extracellular matrix (ECM) network microenvironment from fibrillary collagen types I, III and V to collagens IV and VI, which affected the cells niche. The changes in ECM are translated for cytoskeleton remodeling according to cell fate-determining mechanisms. We quantified the cytoskeleton rearrangement of long oriented actin fibers or short cortical and disorganized fibers, associated with LDs accumulation in adipocytes. Developing in vitro models and analytical methods enable us to study differentiation into adipocytes that will advance our understanding regarding the niche conditions that affect adipogenesis. Consequently, this will enable the development of new modalities to prevent obesity and its deleterious outcomes and to develop potential treatments to battle pathophysiology-related diseases.

Adipogenesis and lipid production in adipocytes subjected to sustained tensile deformations and elevated glucose concentration: a living cell-scale model system of diabesity.

Adipocyte fate commitment is characterized by morphological changes of fibroblastic pre-adipocyte cells, and specifically by accumulation of lipid droplets (LDs) as part of the adipogenesis metabolism. Formation of LDs indicates the production of triglycerides from glucose through an insulin-regulated glucose internalization process. In obesity, adipocytes typically become insulin resistant, and glucose transport into the cells is impaired, resulting in type 2 diabetes. In the present study, we monitored the adipogenesis in 3T3-L1 cultured cells exposed to high (450 mg/dL hyperglycemia) and low (100 mg/dL physiological) glucose concentrations, in a novel cell culture model system of diabesity. In addition to glucose conditions, cells were concurrently exposed to different substrate tensile strains (12% and control) based on our prior work which revealed that adipogenesis is accelerated in cultures subjected to static, chronic substrate tensile deformations. Phase-contrast images were taken throughout the adipogenesis process (3 weeks) and were analyzed by an image processing algorithm which quantitatively monitors cell differentiation and lipid accumulation (number of LDs per cell and their radius as well as cell size and shape). The results indicated that high glucose concentrations and substrate tensile strains delivered to adipocytes accelerated lipid production by 1.7- and 1.4-fold, respectively. In addition, significant changes in average cell projected area and in other morphological attributes were observed during the differentiation process. The importance of this study is in characterizing the adipogenesis parameters as potential read-outs that can predict the occurrence of insulin resistance in the development of diabesity.

Beware of the toilet: The risk for a deep tissue injury during toilet sitting.

A pressure injury (PrI) compromises quality of life and can be life-threatening. The fundamental cause of PrIs is sustained deformations in weight-bearing soft tissues, e.g., during prolonged sitting on inadequate surfaces such as a toilet seat. In nursing homes and geriatric facilities, patients need assistance using the restroom, and patients being left on the toilet for tens-of-minutes is a real-world scenario, unfortunately. Nevertheless, there are no published studies regarding sustained tissue loads during toilet sitting and their effects on tissue physiology. Here, the biomechanical and microcirculatory responses of the buttock tissues to toilet sitting were investigated using finite element modeling and cutaneous hemodynamic measurements, to explore the potential etiology of PrIs occurring on the toilet. We found that prolonged sitting on toilet seats involves a potential risk for PrI development, the extent of which is affected by the seat design. Additionally, we found that specialized toilet seat cushions are able to reduce this risk, by lowering instantaneous tissue exposures to internal stresses (by up to 88%) and maintaining reduced interface pressures. Furthermore, hemodynamic variables were altered during the toilet sitting; in particular, tcPO2 was decreased by 49% ± 7% (44 ± 2[mmHg] to 22 ± 4[mmHg]) during sitting. The current study confirms that investing in expensive PrI prevention (PIP) products is likely to be ineffective for an immobilized patient who is left to sit on a bare toilet seat for long times. This argument highlights the need for a holistic-care approach, employing PIP devices that span across the entire environment where bodyweight forces apply to tissues.