Bioengineering considerations in the prevention of medical device-related pressure ulcers.

BACKGROUND: In recent years, it has become increasingly apparent that medical device-related pressure ulcers represent a significant burden to both patients and healthcare providers. Medical devices can cause damage in a variety of patients from neonates to community based adults. To date, devices have typically incorporated generic designs with stiff polymer materials, which impinge on vulnerable soft tissues. As a result, medical devices that interact with the skin and underlying soft tissues can cause significant deformations due to high interface pressures caused by strapping or body weight. METHODS: This review provides a detailed analysis of the latest bioengineering tools to assess device related skin and soft tissue damage and future perspectives on the prevention of these chronic wounds. This includes measurement at the device-skin interface, imaging deformed tissues, and the early detection of damage through biochemical and biophysical marker detection. In addition, we assess the potential of computational modelling to provide a means for device design optimisation and material selection. INTERPRETATION: Future collaboration between academics, industrialists and clinicians should provide the basis to improve medical device design and prevent the formation of these potentially life altering wounds. Ensuring clinicians report devices that cause pressure ulcers to regulatory agencies will provide the opportunity to identify and improve devices, which are not fit for purpose.

Early identification of wound infection: understanding wound odour.

Malodorous wounds can be distressing for patients and their families, negatively impacting on quality-of-life outcomes. For health professionals malodorous wounds can also cause distress manifesting in feelings of disgust when faced with a wound emitting an unpleasant or repulsive odour. There has been investigation into the management of controlling odour particularly in relation to fungating wounds. However, there is limited research that explores techniques for early identification and recognition of wound odours that may be indicative of infection. Electronic nose technology has received some attention, but to date has not been integrated into either diagnostics of infection in wounds or education of health professionals to prepare them for the realities of clinical practice.

Clinical and biomechanical perspectives on pressure injury prevention research: The case of prophylactic dressings.

In this perspective paper, we discuss clinical and biomechanical viewpoints on pressure injury (or pressure ulcer) prevention research. We have selected to focus on the case of prophylactic dressings for pressure injury prevention, and the background of the historical context of pressure injury research, as an exemplar to illuminate some of the good and not so good in current biomechanical and clinical research in the wound prevention and care arena. Investigators who are conducting medical or clinical research in academia, in medical settings or in industry to determine the efficacy of wound prevention and care products could benefit from applying some basic principles that are detailed in this paper, and that should leverage the research outcomes, thereby contributing to setting higher standards in the field.

Modelling the immune system response to epithelial wound infections.

In this paper, a cell-colony based formalism for the healing of superficial wounds is presented. The paper incorporates the migration, proliferation, and death of constituent cells, in the context of wound healing. The present study considers wound healing under ischemic conditions where a bacterial infection develops, which impairs the motility of the constituent cells. In this work, the performance of the immune response system is incorporated in the sense that migrating leukocyte are modelled which engulf the infectious pathogens. The model is based on both deterministic and stochastic principles. Simulation results are discussed in a biological context.

Semi-stochastic cell-level computational modelling of cellular forces: application to contractures in burns and cyclic loading.

A phenomenological model is formulated to model cellular forces on extracellular material. The model is capable of modelling both expansion and contractile forces. This work is based on the assumption of linear elasticity, which allows a superposition argument to arrive at fundamental expressions for cellular forces. It is also shown how the cellular forces can be implemented using different strategies, as well as an extension to cellular point sources. Illustrations are given for modelling a (permanent) contraction (e.g. a contracture) of burns and for cyclic loading by the cells.

Towards a Mathematical Formalism for Semi-stochastic Cell-Level Computational Modeling of Tumor Initiation.

A phenomenological model is formulated to model the early stages of tumor formation. The model is based on a cell-based formalism, where each cell is represented as a circle or sphere in two-and three dimensional simulations, respectively. The model takes into account constituent cells, such as epithelial cells, tumor cells, and T-cells that chase the tumor cells and engulf them. Fundamental biological processes such as random walk, haptotaxis/chemotaxis, contact mechanics, cell proliferation and death, as well as secretion of chemokines are taken into account. The developed formalism is based on the representation of partial differential equations in terms of fundamental solutions, as well as on stochastic processes and stochastic differential equations. We also take into account the likelihood of seeding of tumors. The model shows the initiation of tumors and allows to study a quantification of the impact of various subprocesses and possibly even of various treatments.

Semi-stochastic cell-level computational modeling of the immune system response to bacterial infections and the effects of antibiotics.

A mathematical model for the immune system response to bacterial infections is proposed. The formalism is based on modeling the chemokine-determined transmigration of leukocytes from a venule through the venule walls and the subsequent in-tissue migration and engulfment of the pathogens that are responsible for the infection. The model is based on basic principles, such as Poiseuille blood flow through the venule, fundamental solutions of the diffusion-reaction equation for the concentration field of pathogen-released chemokines, linear chemotaxis of the leukocytes, random walk of pathogens, and stochastic processes for the death and division of pathogens. Thereby, a computationally tractable and, as far as we know, original framework has been obtained, which is used to incorporate the interaction of a substantial number of leukocytes and thereby to unravel the significance of biological processes and parameters regarding the immune system response. The developed model provides a neat way for visualization of the biophysical mechanism of the immune system response. The simulations indicate a weak correlation between the immune system response in terms of bacterial clearing time and the leukocyte stiffness, and a significant decrease in the clearing time with increasing in-blood leukocyte density, decreasing pathogen motility, and increasing venule wall transmissivity. Finally, the increase in the pathogen death rate and decrease in pathogen motility induce a decrease in the clearing time of the infection. The adjustment of the latter two quantities mimic the administration of antibiotics.

A phenomenological model for chemico-mechanically induced cell shape changes during migration and cell-cell contacts.

A phenomenological model for the evolution of shape transition of cells is considered. These transitions are determined by the emission of growth-factors, as well as mechanical interaction if cells are subjected to hard impingement. The originality of this model necessitates a formal treatment of the mathematical model, as well as the presentation of elementary cases in order to illustrate the consistence of the model. We will also show some small-scale relevant applications.

A semi-stochastic cell-based model for in vitro infected 'wound' healing through motility reduction: a simulation study.

We consider the migration and viability of individual cells in bacterial-infected cell colonies. Cell movement is assumed to take place as a result of sensing the strain energy density as a mechanical stimulus. The model is based on tracking the motion and viability of each individual cell in a cell colony, and the formalism was published in an earlier paper. The present innovations are an application to a simulation of a 'wound healing assay' in which bacteria infect the wound through impairing the motility of cells and an extension with effects from inertia. Though based on simple principles, the model is based on experiments on living fibroblasts on a flat substrate.

A semi-stochastic cell-based formalism to model the dynamics of migration of cells in colonies.

We consider the movement and viability of individual cells in cell colonies. Cell movement is assumed to take place as a result of sensing the strain energy density as a mechanical stimulus. The model is based on tracking the displacement and viability of each individual cell in a cell colony. Several applications are shown, such as the dynamics of filling a gap within a fibroblast colony and the invasion of a cell colony. Though based on simple principles, the model is qualitatively validated by experiments on living fibroblasts on a flat substrate.

A pilot study of a phenomenological model of adipogenesis in maturing adipocytes using Cahn-Hilliard theory.

We consider the accumulation and formation of lipid droplets in an adipocyte cell. The process incorporates adipose nucleation (adipogenesis) and growth. At later stages, there will be merging of droplets and growth of larger droplets at the expense of the smaller droplets, which will essentially undergo lipolysis. The process is modeled by the use of the Cahn-Hilliard equation, which is mass-conserving and allows the formation of secondary phases in the context of spinodal decomposition. The volume of fluid (VOF) method is used to determine the total area that is occupied by the lipids in a given cross section. Further, we present an algorithm, applicable to all kinds of grids (structured or unstructured) in two spatial dimensions, to count the number of lipid droplets and the portion of the domain of computation that is occupied by the lipid droplets as a function of time during the process. The results are preliminary and are validated from a qualitative point using experiments carried out on cell cultures. It turns out that the Cahn-Hilliard theory can model many of the features during adipogenesis qualitatively.

Effects of sitting postures on risks for deep tissue injury in the residuum of a transtibial prosthetic-user: a biomechanical case study.

Transtibial amputation prosthetic-users are at risk of developing deep tissue injury (DTI) while donning their prosthesis for prolonged periods; however, no study addresses the mechanical loading of the residuum during sitting with a prosthesis. We combined MRI-based 3D finite element modelling of a residuum with an injury threshold and a muscle damage law to study risks for DTI in one sitting subject in two postures: 30°-knee-flexion vs. 90°-knee-flexion. We recorded skin-socket pressures, used as model boundary conditions. During the 90°-knee-flexion simulations, major internal muscle injuries were predicted (>1000 mm(3)). In contrast, the 30°-knee-flexion simulations only produced minor injury ( < 14 mm(3)). Predicted injury rates at 90°-knee-flexion were over one order of magnitude higher than those at 30°-knee-flexion. We concluded that in this particular subject, prolonged 90°-knee-flexion sitting theoretically endangers muscle viability in the residuum. By expanding the studies to large subject groups, this research approach can support development of guidelines for DTI prevention in prosthetic-users.

Surgical and morphological factors that affect internal mechanical loads in soft tissues of the transtibial residuum.

The residual limb of transtibial amputation (TTA) prosthetic users is threatened daily by pressure ulcers (PU) and deep tissue injury (DTI) caused mainly by sustained mechanical strains and stresses. Several risk factors dominate the extent of internal tissue loads in the residuum. In this study, we developed a set of three-dimensional finite element (FE) models that were variants of a patient-specific FE model, built from magnetic resonance imaging scans. The set of FE modes was utilized to assess the impact of the following risk factors on the strain/stress distribution in the muscle flap: (i) the tibial length, (ii) the tibial bevelment, (iii) a fibular osteophyte, (iv) the mechanical properties of the muscle, and (v) scarring in different locations and depths. A total of 12 nonlinear FE model configurations, representing variations in these factors, were built and solved. We present herein calculations of compression, tension and shear strains and stresses, von Mises stresses, and strain energy density averaged in critical locations in the muscle flap as well as volumes of concentration of elevated stresses in these areas. Our results overall show higher stresses accumulating in the bone proximity rather than in outlying soft tissues. The longer bone configurations spread the loads toward the external surfaces of the muscle flap. When shortening the truncated bones from 11.2 to 9.2 cm, the von Mises stresses at the distal edges of the bones were relieved considerably (by up to 80%), which indicates a predicted decreased risk for DTI. Decreasing the tibial bevelment mildly, from 52.3 degrees to 37.7 degrees caused propagation of internal stresses from the bone proximity toward the more superficial soft tissues of the residuum, thereby also theoretically reducing the risk for DTI. An osteophyte at the distal fibular end increased the strain and stress distributions directly under the fibula but had little effect (<1%) on stresses at other sites, e.g., under the tibia. Elevation of muscle stiffness (instantaneous shear modulus increase from 8.5 to 16.2 kPa), simulating variation between patients, and muscle flap contraction or spasm, showed the most substantial effect by an acute rise of the von Mises stresses at the bone proximity. The mean von Mises stresses at the bone proximity were approximately twofold higher in the contracted/spastic muscle when compared to the flaccid muscle. Locating a surgical scar in different sites and depths of the residuum had the least influence on the overall loading of the muscle flap (where stresses changed by <7%). Pending further validation by epidemiological PU and DTI risk factor studies, the conclusions of this study can be incorporated as guidelines for TTA surgeons, physical therapists, prosthetists, and the TTA patients themselves to minimize the onset of PU and DTI in this population. Additionally, the present analyses can be used to guide or focus epidemiological research of PU and DTI risk factors in the TTA population.

Patient-specific analyses of deep tissue loads post transtibial amputation in residual limbs of multiple prosthetic users.

Active transtibial amputation (TTA) patients are at risk for developing pressure ulcers (PU) and deep tissue injury (DTI) while using their prosthesis. It is therefore important to obtain knowledge of the mechanical state in the internal soft tissues of the residuum, as well as knowledge of the mechanical state upon its surface. Our aim was to apply patient-specific MRI-based non-linear finite element (FE) models to quantify internal strains in TTA prosthetic users (n=5) during load-bearing. By further employing a strain injury threshold for skeletal muscle, we identified patients susceptible to DTI. The geometrical characteristics of the residuum of the TTA participants varied substantially between patients, e.g. the residuum lengths were 7.6, 8.1, 9.2, 11.5 and 13.3cm. We generally found that internal strains were higher in the bone proximity than in the muscle flap periphery. The highest strains, which in some patients exceeded 50% (engineering strain) for compressive, tensile and shear strains, were found in the shortest residual limbs, i.e. the 7.6 and 8.1cm-long limbs. Correspondingly, the lowest strains were found in the 13.3cm-long residuum, which had the bulkiest muscle flap. Yet, even in the case of a long residuum, about a third of the soft tissue volume at the distal tibial proximity area was occupied by large (>5%) internal compressive, tensile and shear strains. For both patients with shorter residual limbs, the internal principal compressive strains above 5% occupied almost the entire distal tibial proximity area. For a patient whose distal tibial end was flat (non-beveled), internal strains were more uniformly distributed, compared to the strain distributions in the other models, where focal elevated strains accumulated in the bone proximity. We found no muscle strains above the immediate injury threshold, indicating that all patients were not at immediate risk for DTI. Two patients whose residuum fat padding was minimal to none, were the only ones identified as theoretically prone to DTI at long (>3h) continuous weight-bearing periods. We conclude that there is a wide variability in internal mechanical conditions between residual limbs across subjects, which necessitates patient-specific quantitative analyses of internal mechanical states in TTA patients, to assess the mechanical performance of the reconstructed limb and in particular, the individual risk for deep PU or DTI.

Reswick and Rogers pressure-time curve for pressure ulcer risk. Part 2.

In part one of this article, the concepts of an injury threshold were explained and it was shown that the Reswick and Rogers pressure-time curve is inaccurate at the extremes of the timescale. It was also shown that their curve cannot be used for studying deep tissue injuries, and that it is likely to be irrelevant for studying most pressure ulcers. The second part of this article describes recent research work focusing on tissue injury thresholds as related to pressure ulcers, with particular emphasis on thresholds that are specific for deep tissue injuries. Clinical implications are also discussed, with particular reference to patients who are obese and those with muscle atrophy.

Time-related PDL: viscoelastic response during initial orthodontic tooth movement of a tooth with functioning interproximal contact-a mathematical model.

Most anteroposterior orthodontic movements of posterior teeth have to overcome the "resistance" of adjacent teeth with functioning interproximal contacts. The aim of this study was to develop a mathematical model describing initial posterior tooth movement associated with functioning interproximal contacts in relation to the viscoelastic mechanical behavior of the human periodontal ligament (PDL). A linear viscoelastic 2D mathematical model was modified to depict tipping movement around the center of rotation (C(rot)) of a premolar where tipping is restrained by adjacent teeth. Equilibrium equations were applied taking into account the sagittal moment developed around the C(rot). The constants of the model were analyzed and applied to a numerical model that can simulate short-term tooth creep movement caused by a tipping force. Changes in force magnitude (0.5-3N) and crown length (6-10mm) were analyzed until no movement was observed (steady state). Premolar displacement in contact with adjacent teeth showed a non-linear progression over time with an initial sharp tipping movement followed by a transient period of 2.6-7.1min. As tipping force increased the transient period increased. A similar but smaller effect was observed with an increase in crown length. The premolar initial displacement within the arch (3.2-19.5microm) is about seven-fold smaller than retraction/protraction movement of an incisor. These suggest reduction in tooth displacement when functioning interproximal contact is present and clinically recommend establishing a space in the direction of tooth displacement before tooth movement.

Internal mechanical conditions in the soft tissues of a residual limb of a trans-tibial amputee.

Most trans-tibial amputation (TTA) patients use a prosthesis to retain upright mobility capabilities. Unfortunately, interaction between the residual limb and the prosthetic socket causes elevated internal strains and stresses in the muscle and fat tissues in the residual limb, which may lead to deep tissue injury (DTI) and other complications. Presently, there is paucity of information on the mechanical conditions in the TTA residual limb during load-bearing. Accordingly, our aim was to characterize the mechanical conditions in the muscle flap of the residual limb of a TTA patient after donning the prosthetic socket and during load-bearing. Knowledge of internal mechanical conditions in the muscle flap can be used to identify the risk for DTI and improve the fitting of the prosthesis. We used a patient-specific modelling approach which involved an MRI scan, interface pressure measurements between the residual limb and the socket of the prosthesis and three-dimensional non-linear large-deformation finite-element (FE) modelling to quantify internal soft tissue strains and stresses in a female TTA patient during static load-bearing. Movement of the truncated tibia and fibula during load-bearing was measured by means of MRI and used as displacement boundary conditions for the FE model. Subsequently, we calculated the internal strains, strain energy density (SED) and stresses in the muscle flap under the truncated bones. Internal strains under the tibia peaked at 85%, 129% and 106% for compression, tension and shear strains, respectively. Internal strains under the fibula peaked at substantially lower values, that is, 19%, 22% and 19% for compression, tension and shear strains, respectively. Strain energy density peaked at the tibial end (104kJ/m(3)). The von Mises stresses peaked at 215kPa around the distal end of the tibia. Stresses under the fibula were at least one order of magnitude lower than the stresses under the tibia. We surmise that our present patient-specific modelling method is an important tool in understanding the etiology of DTI in the residual limbs of TTA patients.

A three dimensional heart model based on anatomically aligned trusses.

A new approach for modeling and simulating the contraction of the heart is presented. The model is based on anatomical images and accounts for cardiac muscle fibers and their orientation. The heart is modeled as a structure built of trusses, each representing a group of myofibers with calculated deformations using matrix structural analysis. Three elements are represented; these are the contractile cardiac muscle, the elastic passive collagen, and intracardiac blood interacting with the heart's preload and afterload. Incompressibility of each element is preserved. The conduction system is simulated in the model by transferring the activating signal from one element to another or by Purkinje fibers activation. The method was demonstrated using a three-dimensional one-layer geometrical ventricle with orthogonal fibers and with anatomically oriented fibers.

Pressure ulcers and deep tissue injury: a bioengineering perspective.

Wheelchair users are highly susceptible to deep tissue injury. Interface pressures are unlikely to predict this, and an alternative assessment approach is needed that can easily monitor internal mechanical stresses and deformations.