A review of foot finite element modelling for pressure ulcer prevention in bedrest: Current perspectives and future recommendations.

Pressure ulcers (PUs) are a major public health challenge, having a significant impact on healthcare service and patient quality of life. Computational biomechanical modelling has enhanced PU research by facilitating the investigation of pressure responses in subcutaneous tissue and skeletal muscle. Extensive work has been undertaken on PUs on patients in the seated posture, but research into heel ulcers has been relatively neglected. The aim of this review was to address the key challenges that exist in developing an effective FE foot model for PU prevention and the confusion surrounding the wide range of outputs reported. Nine FE foot studies investigating heel ulcers in bedrest were identified and reviewed. Six studies modelled the posterior part of the heel, two included the calf and foot, and one modelled the whole body. Due to the complexity of the foot anatomy, all studies involved simplification or assumptions regarding parts of the foot structure, boundary conditions and material parameters. Simulations aimed to understand better the stresses and strains exhibited in the heel soft tissues of the healthy foot. The biomechanical properties of soft tissue derived from experimental measurements are critical for developing a realistic model and consequently guiding clinical decisions. Yet, little to no validation was reported in each of the studies. If FE models are to address future research questions and clinical applications, then sound verification and validation of these models is required to ensure accurate conclusions and prediction of patient outcomes. Recommendations and considerations for future FE studies are therefore proposed.

An evaluation of dermal microcirculatory occlusion under repeated mechanical loads: Implication of lymphatic impairment in pressure ulcers.

OBJECTIVE: Pressure ulcers are caused by prolonged mechanical loads deforming the underlying soft tissues. However, the mechanical loads for microcirculatory occlusion are unknown. The present study was designed to characterize the simultaneous response of microvascular and lymphatic structures under repeated mechanical loading. METHODS: The effects of two distinct loading/unloading cycles involving (a) incremental pressures 30, 60, and 90 mmHg and (b) three repeated cycles of 30 mmHg were evaluated on a cohort of able-bodied volunteers. Microvascular response involved the monitoring of transcutaneous gas tensions, while dermal lymphatic activity was estimated from near-infrared imaging. Responses were compared during each load and recovery cycle. RESULTS: Changes in microvascular response were dependent on the load magnitudes, with 30 mmHg resulting in a reduction in oxygen tension only, while 90 mmHg affected both oxygen and carbon dioxide values in most cases (54%). By contrast, lymphatics revealed near total occlusion at 30 mmHg. Although there were intersubject differences, temporal trends consistently revealed partial or full impairment under load, with recovery during off-loading. CONCLUSIONS: The pressure required to cause microcirculatory occlusion differed between individuals, with lymphatic impairment occurring at a lower pressure to that of microvascular vessels. This highlights the need for personalized care strategies and regular off-loading of vulnerable tissues.

Magnetic resonance elastography of skeletal muscle deep tissue injury.

The current state-of-the-art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury development is therefore highly desired. In this paper we quantified the spatial-temporal changes in mechanical properties upon damage development and recovery in a rat model of deep tissue injury. Deep tissue injury was induced in nine rats by two hours of sustained deformation of the tibialis anterior muscle. Magnetic resonance elastography (MRE), T2 -weighted, and T2 -mapping measurements were performed before, directly after indentation, and at several timepoints during a 14-day follow-up. The results revealed a local hotspot of elevated shear modulus (from 3.30 ± 0.14 kPa before to 4.22 ± 0.90 kPa after) near the center of deformation at Day 0, whereas the T2 was elevated in a larger area. During recovery there was a clear difference in the time course of the shear modulus and T2 . Whereas T2 showed a gradual normalization towards baseline, the shear modulus dropped below baseline from Day 3 up to Day 10 (from 3.29 ± 0.07 kPa before to 2.68 ± 0.23 kPa at Day 10, P < 0.001), followed by a normalization at Day 14. In conclusion, we found an initial increase in shear modulus directly after two hours of damage-inducing deformation, which was followed by decreased shear modulus from Day 3 up to Day 10, and subsequent normalization. The lower shear modulus originates from the moderate to severe degeneration of the muscle. MRE stiffness values were affected in a smaller area as compared with T2 . Since T2 elevation is related to edema, distributing along the muscle fibers proximally and distally from the injury, we suggest that MRE is more specific than T2 for localization of the actual damaged area.

The Mechanical Contribution of Vimentin to Cellular Stress Generation.

Contractile stress generation by adherent cells is largely determined by the interplay of forces within their cytoskeleton. It is known that actin stress fibers, connected to focal adhesions, provide contractile stress generation, while microtubules and intermediate filaments provide cells compressive stiffness. Recent studies have shown the importance of the interplay between the stress fibers and the intermediate filament vimentin. Therefore, the effect of the interplay between the stress fibers and vimentin on stress generation was quantified in this study. We hypothesized that net stress generation comprises the stress fiber contraction combined with the vimentin resistance. We expected an increased net stress in vimentin knockout (VimKO) mouse embryonic fibroblasts (MEFs) compared to their wild-type (vimentin wild-type (VimWT)) counterparts, due to the decreased resistance against stress fiber contractility. To test this, the net stress generation by VimKO and VimWT MEFs was determined using the thin film method combined with sample-specific finite element modeling. Additionally, focal adhesion and stress fiber organization were examined via immunofluorescent staining. Net stress generation of VimKO MEFs was three-fold higher compared to VimWT MEFs. No differences in focal adhesion size or stress fiber organization and orientation were found between the two cell types. This suggests that the increased net stress generation in VimKO MEFs was caused by the absence of the resistance that vimentin provides against stress fiber contraction. Taken together, these data suggest that vimentin resists the stress fiber contractility, as hypothesized, thus indicating the importance of vimentin in regulating cellular stress generation by adherent cells.

Adaptation of a MR imaging protocol into a real-time clinical biometric ultrasound protocol for persons with spinal cord injury at risk for deep tissue injury: A reliability study.

BACKGROUND: High strain in soft tissues that overly bony prominences are considered a risk factor for pressure ulcers (PUs) following spinal cord impairment (SCI) and have been computed using Finite Element methods (FEM). The aim of this study was to translate a MRI protocol into ultrasound (US) and determine between-operator reliability of expert sonographers measuring diameter of the inferior curvature of the ischial tuberosity (IT) and the thickness of the overlying soft tissue layers on able-bodied (AB) and SCI using real-time ultrasound. MATERIAL AND METHODS: Part 1: Fourteen AB participants with a mean age of 36.7 ± 12.09 years with 7 males and 7 females had their 3 soft tissue layers in loaded and unloaded sitting measured independently by 2 sonographers: tendon/muscle, skin/fat and total soft tissue and the diameter of the IT in its short and long axis. Part 2: Nineteen participants with SCI were screened, three were excluded due to abnormal skin signs, and eight participants (42%) were excluded for abnormal US signs with normal skin. Eight SCI participants with a mean age of 31.6 ± 13.6 years and all male with 4 paraplegics and 4 tetraplegics were measured by the same sonographers for skin, fat, tendon, muscle and total. Skin/fat and tendon/muscle were computed. RESULTS: AB between-operator reliability was good (ICC = 0.81-0.90) for 3 soft tissues layers in unloaded and loaded sitting and poor for both IT short and long axis (ICC = -0.028 and -0.01). SCI between-operator reliability was good in unloaded and loaded for total, muscle, fat, skin/fat, tendon/muscle (ICC = 0.75-0.97) and poor for tendon (ICC = 0.26 unloaded and ICC = -0.71 loaded) and skin (ICC = 0.37 unloaded and ICC = 0.10). CONCLUSION: A MRI protocol was successfully adapted for a reliable 3 soft tissue layer model and could be used in a 2-D FEM model designed to estimate soft tissue strain as a novel risk factor for the development of a PU.

3D Fiber Orientation in Atherosclerotic Carotid Plaques.

Atherosclerotic plaque rupture is the primary trigger of fatal cardiovascular events. Fibrillar collagen in atherosclerotic plaques and their directionality are anticipated to play a crucial role in plaque rupture. This study aimed assessing 3D fiber orientations and architecture in atherosclerotic plaques for the first time. Seven carotid plaques were imaged ex-vivo with a state-of-the-art Diffusion Tensor Imaging (DTI) technique, using a high magnetic field (9.4Tesla) MRI scanner. A 3D spin-echo sequence with uni-polar diffusion sensitizing pulsed field gradients was utilized for DTI and fiber directions were assessed from diffusion tensor measurements. The distribution of the 3D fiber orientations in atherosclerotic plaques were quantified and the principal fiber orientations (circumferential, longitudinal or radial) were determined. Overall, 52% of the fiber orientations in the carotid plaque specimens were closest to the circumferential direction, 34% to the longitudinal direction, and 14% to the radial direction. Statistically no significant difference was measured in the amount of the fiber orientations between the concentric and eccentric plaque sites. However, concentric plaque sites showed a distinct structural organization, where the principally longitudinally oriented fibers were closer to the luminal side and the principally circumferentially oriented fibers were located more abluminally. The acquired unique information on 3D plaque fiber direction will help understanding pathobiological mechanisms of atherosclerotic plaque progression and pave the road to more realistic biomechanical plaque modeling for rupture assessment.

A new method to evaluate the effects of shear on the skin.

Currently, pressure ulcer preventive strategies focus mainly on pressure redistribution. Little attention is paid to reduce the harmful effects of shear-force, because little is known about pathophysiological aspects of shear-force. Even today, no method to measure the effects of shear-force on the skin is available. Therefore, the aim of this study was to investigate the response to shear-forces in terms of analyzing a noninvasive biomarker and reactive hyperemic parameter measured at the skin of healthy participants. A physical model was developed to produce a combination of pressure and shear or pressure alone on the skin. Ten healthy male participants were included and pressure (3.9 kPa) and a combined loading of pressure and shear (2.4 kPa + 14.5 N) was applied at the volar aspect of the forearms for 15 and 30 minutes. A Sebutape sample was used to collect IL-1α and total protein (TP) noninvasively. The reactive hyperemic parameter was derived from a laser Doppler flowmeter. The increase in IL-1α/TP-ratio after a combined loading of pressure and shear for 30 minutes of 6.2 ± 2.5 was significantly higher compared with all other test conditions (p < 0.05). The increase in cutaneous blood cell flux was already significantly higher when a combined loading of pressure and shear was applied for 15 minutes compared with pressure alone. These results shows that the IL-1α/TP-ratio and cutaneous blood cell flux can be used as robust measures of the effect of shear-force on skin in humans. Therefore, this model can be used to evaluate materials aimed at the reduction of shear.

A new pressure ulcer conceptual framework.

AIM: This paper discusses the critical determinants of pressure ulcer development and proposes a new pressure ulcer conceptual framework. BACKGROUND: Recent work to develop and validate a new evidence-based pressure ulcer risk assessment framework was undertaken. This formed part of a Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research. The foundation for the risk assessment component incorporated a systematic review and a consensus study that highlighted the need to propose a new conceptual framework. DESIGN: Discussion Paper. DATA SOURCES: The new conceptual framework links evidence from biomechanical, physiological and epidemiological evidence, through use of data from a systematic review (search conducted March 2010), a consensus study (conducted December 2010-2011) and an international expert group meeting (conducted December 2011). IMPLICATIONS FOR NURSING: A new pressure ulcer conceptual framework incorporating key physiological and biomechanical components and their impact on internal strains, stresses and damage thresholds is proposed. Direct and key indirect causal factors suggested in a theoretical causal pathway are mapped to the physiological and biomechanical components of the framework. The new proposed conceptual framework provides the basis for understanding the critical determinants of pressure ulcer development and has the potential to influence risk assessment guidance and practice. It could also be used to underpin future research to explore the role of individual risk factors conceptually and operationally. CONCLUSION: By integrating existing knowledge from epidemiological, physiological and biomechanical evidence, a theoretical causal pathway and new conceptual framework are proposed with potential implications for practice and research.

Developing a pressure ulcer risk factor minimum data set and risk assessment framework.

AIM: To agree a draft pressure ulcer risk factor Minimum Data Set to underpin the development of a new evidenced-based Risk Assessment Framework. BACKGROUND: A recent systematic review identified the need for a pressure ulcer risk factor Minimum Data Set and development and validation of an evidenced-based pressure ulcer Risk Assessment Framework. This was undertaken through the Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research and incorporates five phases. This article reports phase two, a consensus study. DESIGN: Consensus study. METHOD: A modified nominal group technique based on the Research and Development/University of California at Los Angeles appropriateness method. This incorporated an expert group, review of the evidence and the views of a Patient and Public Involvement service user group. Data were collected December 2010-December 2011. FINDINGS: The risk factors and assessment items of the Minimum Data Set (including immobility, pressure ulcer and skin status, perfusion, diabetes, skin moisture, sensory perception and nutrition) were agreed. In addition, a draft Risk Assessment Framework incorporating all Minimum Data Set items was developed, comprising a two stage assessment process (screening and detailed full assessment) and decision pathways. CONCLUSION: The draft Risk Assessment Framework will undergo further design and pre-testing with clinical nurses to assess and improve its usability. It will then be evaluated in clinical practice to assess its validity and reliability. The Minimum Data Set could be used in future for large scale risk factor studies informing refinement of the Risk Assessment Framework.

There is an individual tolerance to mechanical loading in compression induced deep tissue injury.

BACKGROUND: Deep tissue injury is a type of pressure ulcer which originates subcutaneously due to sustained mechanical loading. The relationship between mechanical compression and damage development has been extensively studied in 2D. However, recent studies have suggested that damage develops beyond the site of indentation. The objective of this study was to compare mechanical loading conditions to the associated damage in 3D. METHODS: An indentation test was performed on the tibialis anterior muscle of rats (n = 39). Changes in the form of oedema and structural damage were monitored with MRI in an extensive region. The internal deformations were evaluated using MRI based 3D finite element models. FINDINGS: Damage propagates away from the loaded region. The 3D analysis indicates that there is a subject specific tolerance to compression induced deep tissue injury. INTERPRETATION: Individual tolerance is an important factor when considering the mechanical loading conditions which induce damage.

The free diffusion of macromolecules in tissue-engineered skeletal muscle subjected to large compression strains.

Pressure-related deep tissue injury (DTI) represents a severe pressure ulcer, which initiates in compressed muscle tissue overlying a bony prominence and progresses to more superficial tissues until penetrating the skin. Individual subjects with impaired motor and/or sensory capacities are at high risk of developing DTI. Impaired diffusion of critical metabolites in compressed muscle tissue may contribute to DTI, and impaired diffusion of tissue damage biomarkers may further impose a problem in developing early detection blood tests. We hypothesize that compression of muscle tissue between a bony prominence and a supporting surface locally influences the diffusion capacity of muscle. The objective of this study was therefore, to determine the effects of large compression strains on free diffusion in a tissue-engineered skeletal muscle model. Diffusion was measured with a range of fluorescently labeled dextran molecules (10, 20, 150kDa) whose sizes were representative of both hormones and damage biomarkers. We used fluorescence recovery after photobleaching (FRAP) to compare diffusion coefficients (D) of the different dextrans between the uncompressed and compressed (48-60% strain) states. In a separate experiment, we simulated the effects of local partial muscle ischemia in vivo, by reducing the temperature of compressed specimens from 37 to 34 degrees C. Compared to the D in the uncompressed model system, values in the compressed state were significantly reduced by 47+/-22% (p<0.02). A 3 degrees C temperature decrease further reduced D in the compressed specimens by 10+/-6% (p<0.05). In vivo, the effects of large strains and ischemia are likely to be summative, and hence, the present findings suggest an important role of impaired diffusion in the etiology of DTI, and should also be considered when developing biochemical screening methods for early detection of DTI.

Diffusion measurements in epidermal tissues with fluorescent recovery after photobleaching.

BACKGROUND/PURPOSE: Pressure ulcers are areas of soft tissue breakdown, resulting from sustained mechanical loading of the skin and underlying tissues. Measuring biochemical markers that are released upon mechanical loading by the epidermis seems a promising method for objective risk assessment of the development of pressure ulcers. This risk assessment method will better determine the risk of a patient to develop pressure ulcers than the risk score lists currently used. So far, experimental studies have been performed that measure the tissue response in the culture supernatant. To elucidate the transport of the biochemical markers within the epidermis, the diffusion coefficient needs to be established. METHODS: In the current study, fluorescent recovery after photobleaching (FRAP) is used to determine the diffusion coefficient of fluorescent-labeled dextran molecules in human epidermis, porcine epidermis and engineered epidermal equivalents. These dextran molecules have a similar weight to the biochemical markers. RESULTS: Similar diffusion coefficients were found for human and porcine epidermal samples (6.2 x 10(-5)+/-1.2 x 10(-5) and 5.9 x 10(-5)+/-6.1 x 10(-6) mm2/s, respectively), whereas the diffusion coefficient of the engineered epidermal equivalent was significantly lower (2.3 x 10(-5)+/-1.0 x 10(-5) mm2/s). CONCLUSION: The diffusion could be measured in epidermal tissues using FRAP. In the future, the diffusion coefficients obtained in the current study will be used to study the difference between the transport in EpiDerm cultures and in human epidermis.

Linear viscoelastic behavior of subcutaneous adipose tissue.

Subcutaneous adipose tissue contributes to the overall mechanical behavior of the skin. Until today, however, no thorough constitutive model is available for this layer of tissue. As a start to the development of such a model, the objective of this study was to measure and describe the linear viscoelastic behavior of subcutaneous adipose tissue. Although large strains occur in vivo, this work only focuses on the linear behavior to show the applicability of the described methods to adipose tissue. Shear experiments are performed on porcine samples on a rotational rheometer using parallel plate geometry. In the linear viscoelastic regime, up to 0.1% strain, the storage and loss modulus showed a frequency- and temperature-dependent behavior. The ratio between the two moduli, the phase angle, did not show any dependency on temperature and frequency. The shear modulus was found to be 7.5 kPa at 10 rad/s and 37 degrees C. Time-temperature superposition was applicable through shifting the shear modulus horizontally. A power-law function model was introduced to describe both the frequency dependent behavior at constant temperature and the stress relaxation behavior. In addition, the effect of snap freezing as a preservation method was analyzed. Histological examination demonstrated possible tissue damage after freezing, but the mechanical properties did not change. Since results were reproducible, it is concluded that the methods we used are most probably suited to explore the non-linear behavior of subcutaneous adipose tissue.

The non-linear mechanical properties of soft engineered biological tissues determined by finite spherical indentation.

The mechanical properties of soft biological tissues in general and early stage engineered tissues in particular limit the feasibility of conventional tensile tests for their mechanical characterisation. Furthermore, the most important mode in development of deep tissue injury (DTI) is compression. Therefore, an inverse numerical-experimental approach using a finite spherical indentation test is proposed. To demonstrate the feasibility of the approach indentation tests are applied to bio-artificial muscle (BAM) tissue. BAMs are cultured in vitro with (n = 20) or without (n = 12) myoblast cells to quantify the effect of the cells on the passive transverse mechanical properties. Indentation tests are applied up to 80% of the tissue thickness. A non-linear Neo-Hookean constitutive model is fitted to the experimental results for parameter estimation. BAMs with cells demonstrated both stiffer and more non-linear material behaviour than BAMs without cells.

Intrinsic Cell Stress is Independent of Organization in Engineered Cell Sheets.

Understanding cell contractility is of fundamental importance for cardiovascular tissue engineering, due to its major impact on the tissue's mechanical properties as well as the development of permanent dimensional changes, e.g., by contraction or dilatation of the tissue. Previous attempts to quantify contractile cellular stresses mostly used strongly aligned monolayers of cells, which might not represent the actual organization in engineered cardiovascular tissues such as heart valves. In the present study, therefore, we investigated whether differences in organization affect the magnitude of intrinsic stress generated by individual myofibroblasts, a frequently used cell source for in vitro engineered heart valves. Four different monolayer organizations were created via micro-contact printing of fibronectin lines on thin PDMS films, ranging from strongly anisotropic to isotropic. Thin film curvature, cell density, and actin stress fiber distribution were quantified, and subsequently, intrinsic stress and contractility of the monolayers were determined by incorporating these data into sample-specific finite element models. Our data indicate that the intrinsic stress exerted by the monolayers in each group correlates with cell density. Additionally, after normalizing for cell density and accounting for differences in alignment, no consistent differences in intrinsic contractility were found between the different monolayer organizations, suggesting that the intrinsic stress exerted by individual myofibroblasts is independent of the organization. Consequently, this study emphasizes the importance of choosing proper architectural properties for scaffolds in cardiovascular tissue engineering, as these directly affect the stresses in the tissue, which play a crucial role in both the functionality and remodeling of (engineered) cardiovascular tissues.

MRI based 3D finite element modelling to investigate deep tissue injury.

Pressure ulcers occur due to sustained mechanical loading. Deep tissue injury is a severe type of pressure ulcer, which is believed to originate in subcutaneous tissues adjacent to bony prominences. In previous experimental-numerical studies the relationship between internal tissue state and damage development was investigated using a 2D analysis. However, recent studies suggest that a local analysis is not sufficient. In the present study we developed a method to create animal-specific 3D finite element models of an indentation test on the tibialis anterior muscle of rats based on MRI data. A detailed description on how the animal specific models are created is given. Furthermore, two indenter geometries are compared and the influence of errors in determining the indenter orientation on the resulting internal strain distribution in a defined volume of tissue was investigated. We conclude that with a spherically-shaped indenter errors in estimating the indenter orientation do not unduly influence the results of the simulation.

An advanced magnetic resonance imaging perspective on the etiology of deep tissue injury.

Early diagnosis of deep tissue injury remains problematic due to the complicated and multifactorial nature of damage induction and the many processes involved in damage development and recovery. In this paper, we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multiparametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multiparametric in vivo MRI, consisting of T2, T2*, mean diffusivity (MD), and angiography measurements, was applied before, during, and directly after indentation as well as at several time points during a 14-day follow-up. MRI readouts were linked to histological analyses of the damaged tissue. The results showed dynamic change in various MRI parameters, reflecting the histopathological status of the tissue during damage induction and repair. Increased T2 corresponded with edema, muscle cell damage, and inflammation. T2* was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease was reported on the tissue's microstructural integrity and reflected muscle degeneration and edema as well as fibrosis. Angiography provided information on blockage of blood flow during deformation. Our results indicate that the effects of a single damage-causing event of only 2 h of deformation were present up to 14 days. The initial tissue response to deformation, as observed by MRI, starts at the edge of the indentation. The quantitative MRI readouts provided distinct and complementary information on the extent, temporal evolution, and microstructural basis of deep tissue injury-related muscle damage. NEW & NOTEWORTHY We have applied a multiparametric MRI approach linked to histopathology to characterize damage development and remodeling in a rat model of deep tissue injury. Our approach provided several relevant insights in deep tissue injury. Response to damage, as observed by MRI, started at some distance from the deformation. Damage after a single indentation period persisted up to 14 days. The MRI parameters provided distinct and complementary information on the microstructural basis of the damage.

Temporal differences in the influence of ischemic factors and deformation on the metabolism of engineered skeletal muscle.

Prolonged periods of tissue compression may lead to the development of pressure ulcers, some of which may originate in, for example, skeletal muscle tissue and progress underneath intact skin, representing deep tissue injury. Their etiology is multifactorial and the interaction between individual causal factors and their relative importance remain unknown. The present study addressed the relative contributions of deformation and ischemic factors to altered metabolism and viability. Engineered muscle tissue was prepared as previously detailed (14) and subjected to a combination of factors including 0% oxygen, lactic acid concentrations resulting in pH from 5.3 to 7.4, 34% compression, and low glucose levels. Deformation had an immediate effect on tissue viability {[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay}, which increased with time. By contrast, hypoxia evoked metabolic responses (glucose and lactate levels) within 24 h, but viability was only reduced after 48 h. In addition, lactic acidification downregulated tissue metabolism up to an acid concentration ( approximately 23 mM) where metabolism was arrested and cell death enhanced. A similar tissue response was observed during glucose deprivation, which, at negligible concentration, resulted in both a cessation of metabolic activity and a reduction in cell viability. The combination of results suggests that in a short-term (<24 h) deformation, extreme acidification and glucose deprivation increased the level of cell death. By contrast, nonextreme acidification and hypoxia influenced tissue metabolism, but not the development of cell death. These data provide more insight into how compression-induced factors can lead to the onset of deep tissue injury.

Understanding the requirements of self-expandable stents for heart valve replacement: Radial force, hoop force and equilibrium.

A proper interpretation of the forces developed during stent crimping and deployment is of paramount importance for a better understanding of the requirements for successful heart valve replacement. The present study combines experimental and computational methods to assess the performance of a nitinol stent for tissue-engineered heart valve implantation. To validate the stent model, the mechanical response to parallel plate compression and radial crimping was evaluated experimentally. Finite element simulations showed good agreement with the experimental findings. The computational models were further used to determine the hoop force on the stent and radial force on a rigid tool during crimping and self-expansion. In addition, stent deployment against ovine and human pulmonary arteries was simulated to determine the hoop force on the stent-artery system and the equilibrium diameter for different degrees of oversizing.

Computationally Designed 3D Printed Self-Expandable Polymer Stents with Biodegradation Capacity for Minimally Invasive Heart Valve Implantation: A Proof-of-Concept Study.

The evolution of minimally invasive implantation procedures and the in vivo remodeling potential of decellularized tissue-engineered heart valves require stents with growth capacity to make these techniques available for pediatric patients. By means of computational tools and 3D printing technology, this proof-of-concept study demonstrates the design and manufacture of a polymer stent with a mechanical performance comparable to that of conventional nitinol stents used for heart valve implantation in animal trials. A commercially available 3D printing polymer was selected, and crush and crimping tests were conducted to validate the results predicted by the computational model. Finally, the degradability of the polymer was assessed via accelerated hydrolysis.