Fibroblast growth factor-2 bound to specific dermal fibroblast-derived extracellular vesicles is protected from degradation.

Fibroblast growth factor-2 (FGF2) has multiple roles in cutaneous wound healing but its natural low stability prevents the development of its use in skin repair therapies. Here we show that FGF2 binds the outer surface of dermal fibroblast (DF)-derived extracellular vesicles (EVs) and this association protects FGF2 from fast degradation. EVs isolated from DF cultured in the presence of FGF2 harbor FGF2 on their surface and FGF2 can bind purified EVs in absence of cells. Remarkably, FGF2 binding to EVs is restricted to a specific subpopulation of EVs, which do not express CD63 and CD81 markers. Treatment of DF with FGF2-EVs activated ERK and STAT signaling pathways and increased cell proliferation and migration. Local injection of FGF2-EVs improved wound healing in mice. We further demonstrated that binding to EVs protects FGF2 from both thermal and proteolytic degradation, thus maintaining FGF2 function. This suggests that EVs protect soluble factors from degradation and increase their stability and half-life. These results reveal a novel aspect of EV function and suggest EVs as a potential tool for delivering FGF2 in skin healing therapies.

Purification of Extracellular Microvesicles Secreted by Dermal Fibroblasts.

Extracellular vesicles (EVs) secreted by all cells are key players in information transfer within a tissue or organism. With their highly cell-specific protein and RNA content, EVs can propagate cellular signals and modulate distant cells' behavior. Dermal fibroblasts are supportive cells for all skin cells and the roles of their EVs start to come to light only recently. In this chapter, we describe a protocol to isolate small EVs from primary human fibroblast culture using classical differential centrifugation methodology.

Effects of a novel medial meniscus implant on the knee compartments: imaging and biomechanical aspects.

The altered biomechanical function of the knee following partial meniscectomy results in ongoing articular cartilage overload, which may lead to progressive osteoarthritis (OA). An artificial medial meniscus implant (NUsurface® Meniscus Implant, Active Implants LLC., Memphis, TN, USA) was developed to mimic the native meniscus and may provide an effective long-term solution for OA patients, alleviate pain, and restore joint function. The goal of the current study was to investigate the potential effect of an artificial medial meniscus implant on the function of the lateral compartment of the knee and on the potential alterations in load distribution between the two compartments under static axial loading, using advanced piezo-resistive sensors. We used an integrated in situ/in vivo experimental approach combining contact pressure measurements of cadaveric knees with MRI joint space measurements of 72 mild OA patients. We employed this integrated approach to evaluate the mechanical consequences in both the medial (treated) and lateral knee compartments of two levels of meniscectomy and implantation of an artificial meniscus implant. Partial and subtotal meniscectomies of the medial meniscus resulted in statistically significant decrease in contact areas (p = 0.008 and p < 0.0001, respectively) and increased contact pressures in the medial compartment; however, implantation of the artificial meniscus implant restored the average contact pressure to 93 ± 14% of its pre-meniscectomy, intact value. Additionally, we found that neither the two different grades of medial meniscectomies, nor implantation of the artificial medial meniscus implant affected the lateral compartment of the knee. The MRI data from the patient cohort facilitated the integration of real-life clinical results together with the laboratory measurements from our cadaveric study, as these two approaches complement each other. We conclude that the use of the artificial medial meniscus implant may re-establish normal load distribution across the articulating surfaces of the medial compartment and not increase loading across the lateral knee compartment.

Release of sodium pyruvate from sacral prophylactic dressings: A computational model.

The use of sacral dressings for pressure ulcer prevention is growing rapidly. In addition to their passive biomechanical role in pressure and shear reduction, in the near future, prophylactic dressings may also provide active tissue protection by releasing preventive agents or drugs into skin and deeper tissues. We investigated delivery of sodium pyruvate (NaPy) from an active dressing to potentially protect the sacral skin and underlying tissues in addition. We used four finite element model variants describing different skin roughness levels to determine time profiles of NaPy diffusion from the dressing into the skin layers. The NaPy concentrations for the different modelled cases stabilised after 1 to 6.5 hours from the time of application of the dressings, at 1% to 3% of the NaPy concentration in the dressing reservoir, which is considered potent. We conclude that prophylactic sacral dressings have the potential to deliver NaPy into skin and subdermally, to potentially increase soft tissue tolerance to sustained bodyweight-caused cell and tissue deformations. The time durations to achieve the steady-state potent NaPy dermal concentrations are clinically feasible, for example, for preparation of patients for surgery or for use in intensive care units.

Measuring Adult Children's Perceptions of Their Parents' Acceptance and Rejection of Their Sexual Orientation: Initial Development of the Parental Acceptance and Rejection of Sexual Orientation Scale (PARSOS).

The Parental Acceptance and Rejection of Sexual Orientation Scale was administered to 256 self-identified lesbian, gay, bisexual, or queer adults who had been out of the closet to their parents for at least 1 year. Principal component analysis revealed a clear two-component solution: parental acceptance and parental rejection. Findings showed that perceived maternal sexual orientation-specific acceptance was higher, and perceived maternal sexual orientation-specific rejection was lower, for gay/bisexual sons compared to their lesbian/bisexual daughters. Results of regression analyses suggest that both perceived sexual orientation specific acceptance and rejection predicted adult children's psychological symptoms after accounting for perceived global parental acceptance and rejection and the child's gender. The scale's utility for research and practice are noted.

Sacral Soft Tissue Deformations When Using a Prophylactic Multilayer Dressing and Positioning System: MRI Studies.

PURPOSE: The sacrum is the most common location of pressure injuries (PIs) in bedridden patients. The purpose of this study was to measure the effect of specific pressure preventive devices on sacral skeletal muscle, subcutaneous fat, and skin tissue deformations. SUBJECTS AND SETTING: The sample comprised 3 healthy adults residing in a community setting in Tel Aviv, Israel. DESIGN: Descriptive, comparative design. METHODS: Tissue thickness changes of 3 healthy adults were measured using magnetic resonance imaging (MRI) in weight-bearing sacral skin, subcutaneous fat, and muscle. Changes in tissue thickness were compared under the following conditions: (1) lying supine on a rigid surface (unpadded MRI table), (2) lying on a standard foam mattress, (3) lying on a mattress after application of a prophylactic multilayer dressing, and (4) lying on a standard foam mattress with a prophylactic multilayer dressing and a positioning system. One-way analysis of variance and post hoc Tukey-Kramer multiple pairwise comparisons were used to compare outcomes. RESULTS: The mattress, the prophylactic multilayer dressing, and the turning and positioning device when applied together resulted in significantly lower deformation levels of each of the soft tissue layers (ie, skin, subcutaneous fat, and muscle separately) as well as of the total soft tissue bulk, with respect to the rigid MRI table (P < .05). CONCLUSION: Study findings suggest that a combination of preventive interventions may reduce the risk of developing a sacral PI.

A Computer Modeling Study to Assess the Durability of Prophylactic Dressings Subjected to Moisture in Biomechanical Pressure Injury Prevention.

The sacral area is the most common site for pressure injuries (PIs) associated with prolonged supine bedrest. In previous studies, an anisotropic multilayer prophylactic dressing was found to reduce the incidence of PIs and redistribute pressure. The purpose of the current study was to further investigate relationships between design features and biomechanical efficacy of sacral prophylactic dressings. Using computer modeling, the anisotropic multilayer dressing and a hypothetical dressing with different mechanical properties were tested under dry and 3 levels of moist/wet conditions. Sixteen (16) finite element model variants representing the buttocks were developed. The model variants utilized slices of the weight-bearing buttocks of a 28-year-old healthy woman for segmentation of the pelvic bones and soft tissues. Effective stresses and maximal shear stresses in a volume of interest of soft tissues surrounding the sacrum were calculated from the simulations, and a protective endurance (PE) index was further calculated. Resistance to deformations along the direction of the spine when wet was determined by rating simulation outcomes (volumetric exposures to effective stress) for the different dressing conditions. Based on this analysis, the anisotropic multilayer prophylactic dressing exhibited superior PE (80%), which was approximately 4 times that of the hypothetical dressing (22%). This study provides additional important insights regarding the optimal design of prophylactic dressings, especially when exposed to moisture. A next step in research would be to optimize the extent of the anisotropy, particularly the property ratio of stiffnesses (elastic moduli).

Effects of humidity on skin friction against medical textiles as related to prevention of pressure injuries.

Sustained pressure, shear forces, and friction, as well as elevated humidity/moisture, are decisive physical factors in the development of pressure injuries (PIs). To date, further research is needed in order to understand the influence of humidity and moisture on the coefficient of friction (COF) of skin against different types of medical textiles. The aim of this work was to investigate the effects of moisture caused by sweat, urine, or saline on the resulting COF of skin against different textiles used in the medical setting in the context of PI prevention. For that purpose, we performed physical measurements of static COFs of porcine skin followed by finite element (FE) computational modelling in order to illustrate the effect of increased COF at the skin on the resulting strains and stresses deep within the soft tissues of the buttocks. The COF of dry skin obtained for the 3 textiles varied between 0.59 (adult diaper) and 0.91 (polyurethane dressing). In addition, the COF increased with the added moisture in all of the tested cases. The results of the FE simulations further showed that increased COF results in elevated strain energy density and shear strain values in the skin and deeper tissues and, hence, in an increased risk for PI development. We conclude that moisture may accelerate PI formation by increasing the COF between the skin and the medical textile, regardless of the type of the liquid that is present. Hence, reduction of the wetness/moisture between the skin and fabrics in patients at a high risk of developing PIs is a key measure in PI prevention.

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.

Effects of ambient conditions on the risk of pressure injuries in bedridden patients-multi-physics modelling of microclimate.

Scientific evidence regarding microclimate and its effects on the risk of pressure ulcers (PU) remains sparse. It is known that elevated skin temperatures and moisture may affect metabolic demand as well as the mechanical behaviour of the tissue. In this study, we incorporated these microclimate factors into a novel, 3-dimensional multi-physics coupled model of the human buttocks, which simultaneously determines the biothermal and biomechanical behaviours of the buttocks in supine lying on different support surfaces. We compared 3 simulated thermally controlled mattresses with 2 reference foam mattresses. A tissue damage score was numerically calculated in a relevant volume of the model, and the cooling effect of each 1°C decrease of tissue temperature was deduced. Damage scores of tissues were substantially lower for the non-foam mattresses compared with the foams. The percentage tissue volume at risk within the volume of interest was found to grow exponentially as the average tissue temperature increased. The resultant average sacral skin temperature was concluded to be a good predictor for an increased risk of PU/injuries. Each 1°C increase contributes approximately 14 times as much to the risk with respect to an increase of 1 mmHg of pressure. These findings highlight the advantages of using thermally controlled support surfaces as well as the need to further assess the potential damage that may be caused by uncontrolled microclimate conditions on inadequate support surfaces in at-risk patients.

Assessment of the Biomechanical Effects of Prophylactic Sacral Dressings on Tissue Loads: A Computational Modeling Analysis.

The sacrum is the most susceptible anatomical site for developing pressure injuries, including deep tissue injuries, during supine lying. Prophylactic dressings generally are designed to reduce friction, alleviate internal tissue shear, manage the microclimate, and overall cushion the soft tissues subjected to sustained deformations under the sacrum. Using computational modeling, the authors developed a set of 8 magnetic resonance imaging-based, 3-dimensional finite element models of the buttocks of a healthy 28-year-old woman for comparing the biomechanical effects of different prophylactic sacral dressing designs when used during supine lying on a standard hospital foam mattress. Computer simulation data from model variants incorporating an isotropic (same stiffness in every direction) multilayer compliant dressing, an anisotropic (directionally dependent stiffness properties) multilayer compliant dressing, and a completely stiff dressing were compared to control (no dressing). Specific outcome measures that were compared across these simulation cases were strain energy density (SED) and maximal shear stresses in a volume of interest (VOI) of soft tissues surrounding the sacrum. The SED and shear stress measurements were obtained in pure compression loading of the buttocks (ie, simulating a horizontal supine bed rest) and in combined compression-and-shear loads applied to the buttocks (ie, 45˚ Fowler position causing frictional and shear forces) on a standard foam mattress. Compared to the isotropic dressing design, the anisotropic dressing facilitated more soft tissue protection through an additional 11% reduction in exposure to SED at the VOI. In this model, use of the anisotropic compliant dressing resulted in the lowest exposures to internal tissue SED and shear stresses. Research to examine the clinical inference of this modeling technique and studies to compare the effects of prophylactic dressings on healthy volunteers and patients in different positions are warranted.

The contribution of a directional preference of stiffness to the efficacy of prophylactic sacral dressings in protecting healthy and diabetic tissues from pressure injury: computational modelling studies.

The sacral region is the most common site for pressure injuries (PIs) associated with lying in bed, and such sacral PIs often commence as deep tissue injuries (DTIs) that later present as open wounds. In complex patients, diabetes is common. Because, among other factors, diabetes affects connective tissue stiffness properties, making these tissues less able to dissipate mechanical loads through physiological deformations, diabetes is an additional biomechanical risk factor for PIs and DTIs. A preventive measure with established successful clinical outcomes is the use of sacral prophylactic dressings. The objective of this study has been to expand our previous work regarding the modes of action and biomechanical efficacy of prophylactic dressings in protecting the soft tissues adjacent to the sacrum by specifically examining the role of a directional stiffness preference (anisotropy) of the dressing while further accounting for diabetic tissue conditions. Multiple three-dimensional anatomically detailed finite element (FE) model variants representing diabetic tissue conditions were used, and tissue loading state data were compared with healthy tissue simulations. We specifically compared soft tissue exposures to elevated internal shear stresses and strain energy densities (SED) near the sacrum during supine weight bearing on a standard (foam) hospital mattress without a dressing, with a prophylactic dressing lacking directional stiffness preferences and with an anisotropic dressing. Our results have clearly shown that an anisotropic dressing design reduces the peak tissue stresses and exposure to sustained tissue deformations in both healthy and diabetic cases. The present study provides additional important insights regarding the optimal structural and material design of prophylactic dressings, which in turn, informs clinicians and decision makers regarding beneficial features.

Device-related pressure ulcers from a biomechanical perspective.

Pressure ulcers (PUs) in the pediatric population are inherently different from those in adults, in their risk factors and etiology, with more than 50% of the cases related to contact with medical equipment at the care setting. The aims of this study were to: (i) Determine the mechanical loads in the scalp of a newborn lying supine, near a wedged encephalogram electrode or wire, which is deforming the scalp at the occiput. (ii) Evaluate the effect of a doughnut-shaped headrest on the mechanical state of tissues at the same site. We used finite element computational modeling to simulate a realistic three-dimensional head of a newborn interacting with the above devices. We examined effective (von Mises) stresses, shear stresses and strain energy density (SED) in the fat and skin tissues at the occipital region. The interfering wire resulted in the worse mechanical conditions in the soft tissues, compared to the lodged electrode and use of a doughnut-shaped headrest, with 345% and 50% increase in effective stresses in skin and fat tissues, respectively. Considering that elevated and localized tissue deformations, stresses and SED indicate a risk for PUs, our simulations suggest that misplaced medical devices, and using a doughnut-shaped headrest, impose an actual risk for developing device-related PUs. We conclude that guidelines for pediatric clinical care should recommend routine inspection of the medical device placement to prevent harmful contact conditions with the patient. Furthermore, improved design of medical equipment for pediatric settings is needed in order to protect these fragile young patients from PUs.

A multiscale modeling framework for studying the mechanobiology of sarcopenic obesity.

An inactive sedentary lifestyle is a common risk factor contributing to sarcopenic obesity. At the cell scale, sustained mechanical deformations of the plasma membrane (PM) in adipocytes, characterizing chronic static loading in weight-bearing tissues during prolonged sitting or lying, were found to promote adipogenesis. Taking a mechanobiological perspective, we correlated here the macroscale mechanical deformations of weight-bearing adipose tissues (subcutaneous and intramuscular) with mechanical strains developing in the PMs of differentiating adipocytes. An innovative multiscale modeling framework for adipose tissues was developed for this purpose, where the buttocks, adipose tissues, adipocytes and the subcellular components: intracytoplasmic nucleus and lipid droplets as well as the PMs of the cells, were all represented. We found that a positive feedback loop very likely exists and is involved in the onset and progression of sarcopenic obesity, as follows. Adipogenesis in statically deformed adipocytes results in gaining more macroscopic subcutaneous and intramuscular fat mass, which then increases fat deformations macroscopically and microscopically, and hence triggers additional adipogenesis, and so on. Our present study is highly relevant in research of sarcopenic obesity and other adipose-related diseases such as diabetes, since mechanical distortion of adipocytes promotes adipogenesis and fat gain at the different dimensional scales.

Penile compression clamps: A model of the internal mechanical state of penile soft tissues.

AIMS: Prostate cancer is the most frequently diagnosed male cancer and urinary incontinence represents a major consequence following surgery. Penile compression clamps (PCCs) which externally occlude the urethra may be used to manage the incontinence. Despite potential complication of PCCs, such as deformation-inflicted tissue damage, to date, there are no reported biomechanical criteria for design of PCCs, in terms of quantitative parameters for evaluating the safety-versus-efficacy of existing or future designs. METHODS: We developed a set of computational three-dimensional models of the penis, to which compression was applied using five generic PCC designs. The internal mechanical states of the soft tissues of the penis were then analysed using finite element simulations. RESULTS: Stresses in skin, fat, and tunica albuginea regularly exceeded 10 kPa (75 mmHg). Cuff-type and knurl-type PCCs pose the highest potential risks to tissue health with elevated tissue stresses around the entire penile perimeter (cuff) or urethral stress concentrations (knurl). The soft and contoured PCCs produced the lowest values of these mechanical parameters. CONCLUSIONS: The present study identified design characteristics, including envelopment, adaptability, and durability which provide the safest mechanical conditions in the penis and thus minimize the risk of tissue damage while still managing incontinence. Such data should help to design a safer clamp.

Computer Modeling Studies to Assess Whether a Prophylactic Dressing Reduces the Risk for Deep Tissue Injury in the Heels of Supine Patients with Diabetes.

Heels are susceptible to pressure ulcer (PU) development. Some evidence suggests dressings may provide mechanical cushioning, reduce friction with support, and lower localized internal tissue loading, which together may minimize the risk for heel ulcers (HUs). To examine the effect of dressing application on pressure ulcer prevention, 20 computer simulations were performed. Volumetric exposure of soft tissues to effective and shear strains and stresses, with and without a multilayered foam dressing, were assessed, with the extent of tissue exposure considered as measures of the theoretical risk for PUs. The simulations, conducted using the finite element method, provided the mechanical strain and stress magnitudes and distributions in the weight-bearing tissues of the heel, which were visualized and analyzed post-hoc for comparing diabetic to healthy tissue loads with/without prophylactic dressings and at different foot (plantar flexion) postures. The volumetric exposure of the soft tissues of the heel to elevated strains and stresses was considerably reduced by the presence of the dressing, whether diabetic or nondiabetic tissue conditions existed, and for the entire range of the simulated plantar flexion positions. Further, greater plantar flexion, which occurs with elevation of the head of the bed, reduced the volumetric exposure of subcutaneous fat to increased effective strains and stresses, again, particularly when the dressing was on. Specifically, peak (maximum of raw data) effective strains in the soft tissues of the heel decreased by 14.8% and 13.5% with the use of the dressing for healthy persons and persons with diabetes, respectively. Additionally, volumetric exposures of the soft tissues to large effective strains, defined as exposures to >50% strain, decreased substantially, by at least a factor of 2, with the angle of plantar flexion and with respect to a neutral foot posture. Volumetric exposures to midrange (less than 50%) strains were more mildly affected by the foot posture (ie, less than 10% difference was noted across plantar flexion angles). The differences in tissue exposures to strains and stresses between the dressing and nondressing models suggest this dressing provides an important biomechanical protective effect, specifically when diabetic tissue conditions exist. In addition, the data suggest alleviating shear by repositioning the heels after elevating the head of the bed may be critical in order to limit the increase in tissue stress and subsequent PU risk. Randomized, controlled clinical studies to examine the efficacy of dressings for the prevention of heel PUs are warranted.

A Computer Modeling Study to Evaluate the Potential Effect of Air Cell-based Cushions on the Tissues of Bariatric and Diabetic Patients.

Sitting-acquired pressure ulcers (PUs) are a potentially life-endangering complication for wheelchair users who are obese and have diabetes mellitus. The increased body weight and diabetes-related alterations in weight-bearing tissue properties have been identified in the literature to increase the risk for PUs and deep tissue injuries (DTIs). A computer modeling study was conducted to evaluate the biomechanical effect of an air cell-based (ACB) cushion on tissues with increased fat mass and diabetes, which causes altered stiffness properties in connective tissues with respect to healthy tissues. Specifically, 10 finite element (FE) computer simulations were developed with the strain and stress distributions and localized magnitudes considered as measures of the theoretical risk for PUs and DTIs to assess the effects of fat mass and pathological tissue properties on the effective strains and stresses in the soft tissues of buttocks during sitting on an ACB cushion. The FE modeling captured the anatomy of a seated buttocks acquired in an open magnetic resonance imaging examination of an individual with a spinal cord injury. The ACB cushion facilitated a moderate increase in muscle strains (up to 15%) and stresses (up to 30%), and likewise a moderate increase in size of the affected tissue areas with the increase in fat mass, for both diabetic and nondiabetic conditions. These simulation results suggest wheelchair users who are obese and have diabetes may benefit from using an ACB to minimize the increased mechanical strains and stresses in the weight-bearing soft tissues in the buttocks that result from these conditions. Clinical studies to increase understanding about the risk factors of both obesity and diabetes mellitus for the development of PUs and DTIs, as well as robust preclinical comparative studies, may provide much-needed evidence to help clinicians make informed PU prevention and wheelchair cushion decisions for this patient population and other wheelchair-bound individuals.

Adjustability and Adaptability Are Critical Characteristics of Pediatric Support Surfaces.

Significance: Pressure ulcers (PUs) in newborns and children are remarkably different from those in adults, both in their possible causal factors and in the etiology and biomechanical pathways for tissue damage. Recent Advances: Pediatric muscle and fat tissue structures are overall softer than those of adults, making newborns and young children more susceptible to deformation-inflicted injuries at their weight-bearing soft tissues. Critical Issues: The unique medical environment of neonatal and pediatric intensive care units, which is overloaded with medical devices, wiring, tubing, electrodes, and so on, is, in fact, an extrinsic risk factor for device-related PUs, since accidently misplaced tubes, wires, or electrodes can become trapped between the skin and the mattress, causing large sustained soft tissue deformations around them. Future Directions: Mattresses that are being used in neonatal and pediatric intensive care units must be able to respond to frequent movements and changing positions and also be able to effectively adapt and conform around such misplaced tubing or wires, which might contact the body and deform soft tissues. We used computer simulations of a tube caught under a preterm neonate's arm in a supine position to illustrate what adaptability of the support surface means in such cases. Our present simulations indicate that an air-cell-based technology provides considerably better protection against PUs in such cases, as the air-cells are able to locally buckle and conform around objects that are stiffer than the pediatric tissues (e.g., wires, tubes, electrodes), which minimizes exposure to tissue deformations.

Pluripotent stem cells as a cellular model for skin: relevance for physiopathology, cell/gene therapy and drug screening.

The skin represents the largest tissue in the human body. Its external part, the epidermis, accomplishes vital functions such as barrier protection, thermoregulation and immune function. The mammalian skin epidermis has been for decades the paradigm for studying the molecular events that occur in tissue homeostasis and repair. Many genes and signaling pathways have been identified by the use of manipulated transgenic and KO mice. However, despite numerous elegant transgenic mice experiments, absence of an appropriate in vitro model system has hampered the molecular study of the early events responsible for epidermal and dermal commitments, stages at which congenital genetic alterations are responsible for hundreds of rare skin diseases. For most of them, etiology and treatment are still missing. Here we review the last decade of studies aimed at designing cellular models from pluripotent stem cells (PSC) that recapitulate in vitro the main molecular steps of skin formation. As described below, PSC-based models are powerful tools to (i) clarify early molecular events that occur during epithelial/mesenchymal interactions, (ii) produce in large amount skin cells that could become an alternative for cell/gene therapies and (iii) screen for therapeutic compounds to treat genodermatoses.

Contoured Foam Cushions Cannot Provide Long-term Protection Against Pressure-Ulcers for Individuals with a Spinal Cord Injury: Modeling Studies.

OBJECTIVE: To determine changes in internal soft-tissue loads in the buttocks of individuals with a spinal cord injury (SCI), who undergo pathoanatomical changes during the first months and years following the occurrence of the SCI, while sitting on a contoured foam cushion (CFC) that has been fitted close to the time of the injury but has not been replaced in subsequent years. DESIGN: Internal tissue loads in variant buttocks anatomies on a CFC were analyzed by means of finite element computer simulations. The pathoanatomical changes that are characteristic to SCI and were simulated here are: increase in fat tissue mass, intramuscular fat infiltration, muscle atrophy, and combinations of these conditions. SETTING: Computational biomechanical modeling. MAIN RESULTS: Simulating the aforementioned pathoanatomical changes consistently resulted in greater mechanical strain and stress magnitudes and more inhomogeneity in the loading state of muscle and fat tissues, with a more profound effect in fat. The simulations further indicated a clear trend of exacerbation in tissue exposure to loads as the pathoanatomical changes progress chronologically and the CFC is not replaced. CONCLUSIONS: A CFC that has been fitted at a time close to the SCI, but has not been replaced in subsequent years, substantially loses its efficacy in protecting patients from developing pressure ulcers and deep tissue injury in particular.