Background: Defects in α-dystroglycan (DG) glycosylation characterize a group of muscular dystrophies known as dystroglycanopathies. One of the key effectors in the α-DG glycosylation pathway is the glycosyltransferase fukutinrelated protein (FKRP). Mutations in FKRP lead to a large spectrum of muscular dystrophies, including limb girdle muscular dystrophy 2I (LGMD2I). It remains unknown whether stem cell transplantation can promote muscle regeneration and ameliorate the muscle wasting phenotype associated with FKRP mutations.Results: Here we transplanted murine and human pluripotent stem cell-derived myogenic progenitors into a novel immunodeficient FKRP-mutant mouse model by intra-muscular injection. Upon both mouse and human cell transplantation, we observe the presence of donor-derived myofibers even in absence of pre-injury, and the rescue of α-DG functional glycosylation, as shown by IIH6 immunoreactivity. The presence of donor-derived cells expressing Pax7 under the basal lamina is indicative of satellite cell engraftment, and therefore, long-term repopulation potential. Functional assays performed in the mouse-to-mouse cohort revealed enhanced specific force in transplanted muscles compared to PBSinjected controls.Conclusions: Altogether, our data demonstrate for the first time the suitability of a cell-based therapeutic approach to improve the muscle phenotype of dystrophic FKRP-mutant mice.
Surgical repair of hernia and prolapse with prosthetic meshes are well-known to cause pain, infection, hernia recurrence, and mesh contraction and failures. In literature, mesh failure mechanics have been studied with uniaxial, biaxial, and cyclic load testing of dry and wet meshes. Also, extensive experimental studies have been conducted on surrogates, such as non-human primates and rodents, to understand the effect of mesh stiffness, pore size, and knitting patterns on mesh biocompatibility. However, the mechanical properties of such animal tissue surrogates are widely different from human tissues. Therefore, to date, mechanics of the interaction between mesh and human tissues is poorly understood. This work addresses this gap in literature by experimentally and computationally modeling the biomechanical behavior of mesh, sutured to human tissue phantom under tension. A commercially available mesh (Prolene®) was sutured to vaginal tissue phantom material and tested at different uniaxial strains and strain rates. Global and local stresses at the tissue phantom, suture, and mesh were analyzed. The results of this study provide important insights into the mechanics of prosthetic mesh failure and will be indispensable for better mesh design in the future.
Objectives: To identify potential physiologic markers of muscle ischemia to serve as diagnostic indicators of compartment syndrome. We hypothesize that muscle bundles in hypoxic conditions will elicit decreases in potential hydrogen (pH) and increases in lactate and potassium that correlates with decreased muscle twitch forces. Methods: We performed an ex vivo evaluation of individual skeletal muscle bundles obtained from a swine's diaphragm that were exposed to hypoxic conditions and compared with control groups. Over a 4-hour period, we evaluated the following parameters for each muscle bundle: muscle twitch forces and levels of potassium, lactate, and pH. Comparisons between the hypoxic and control groups were calculated at each time point using the 2-tailed Wilcoxon rank sum test for nonparametric data. Longitudinal associations between biomarkers and muscle twitch forces were tested using repeated measures analyses. Results: The hypoxic group elicited more significant decreases in normalized muscle twitch forces than the control group at all time points (0.15 g vs. 0.55 g at 4 hours, P < 0.001). Repeated measures analyses of the hypoxic group demonstrated a statistically significant association between potassium, lactate, and normalized peak force over the course of time. Potassium demonstrated the strongest association with a 1 mmol/L unit increase in potassium associated with a 2.9 g decrease in normalized peak force (95% confidence interval −3.3 to −2.4, P < 0.001). The pH of all muscle baths increased over the course of time at similar rates between the study groups. Conclusions: This study used an ex vivo ischemic skeletal muscle model as a representation for pathophysiologic pathways associated with compartment syndrome. In this experimental approach we were unable to evaluate the pH of the muscle bundles due to continuous applied gassing. Our findings support further evaluations of potassium and lactate levels as potential diagnostic markers.
Skin injury is the most common type of injury, which manifests itself in the form of wounds and cuts. A minor wound repairs itself within a short span of time. However, deep wounds require adequate care and sometime clinical interventions such as surgical suturing for their timely closure and healing. In literature, mechanical properties of skin and other tissues are well known. However, the anisotropic behavior of wounded skin has not been studied yet, specifically with respect to localized overstraining and possibilities of rupture. In the current work, the biomechanics of common skin wound geometries were studied with a biofidelic skin phantom, using uniaxial mechanical testing and Digital Image Correlation (DIC). Global and local mechanical properties were investigated, and possibilities of rupture due to localized overstraining were studied across different wound geometries and locations. Based on the experiments, a finite element (FE) model was developed for a common elliptical skin wound geometry. The fidelity of this FE model was evaluated with simulation of uniaxial tension tests. The induced strain distributions and stress-stretch responses of the FE model correlated very well with the experiments (R2 > 0.95). This model would be useful for prediction of the mechanical response of common wound geometries, especially with respect to their chances of rupture due to localized overstraining. This knowledge would be indispensable for pre-surgical planning, and also in robotic surgeries, for selection of appropriate wound closure techniques, which do not overstrain the skin tissue or initiate tearing.
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