The Experts below are selected from a list of 10938 Experts worldwide ranked by ideXlab platform
Benjamin T. Corona - One of the best experts on this subject based on the ideXlab platform.
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Co-delivery of a laminin-111 supplemented hyaluronic acid based hydrogel with minced Muscle Graft in the treatment of volumetric Muscle loss injury.
PloS one, 2018Co-Authors: Stephen M. Goldman, Beth E. P. Henderson, Thomas J. Walters, Benjamin T. CoronaAbstract:Minced Muscle autoGrafting mediates de novo myofiber regeneration and promotes partial recovery of neuromuscular strength after volumetric Muscle loss injury (VML). A major limitation of this approach is the availability of sufficient donor tissue for the treatment of relatively large VMLs without inducing donor site morbidity. This study evaluated a laminin-111 supplemented hyaluronic acid based hydrogel (HA+LMN) as a putative myoconductive scaffolding to be co-delivered with minced Muscle Grafts. In a rat tibialis anterior Muscle VML model, delivery of a reduced dose of minced Muscle Graft (50% of VML defect) within HA+LMN resulted in a 42% improvement of peak tetanic torque production over unrepaired VML affected limbs. However, the improvement in strength was not improved compared to a 50% minced Graft-only control group. Moreover, histological analysis revealed that the improvement in in vivo functional capacity mediated by minced Grafts in HA+LMN was not accompanied by a particularly robust Graft mediated regenerative response as determined through donor cell tracking of the GFP+ Grafting material. Characterization of the spatial distribution and density of macrophage and satellite cell populations indicated that the combination therapy damps the heightened macrophage response while re-establishing satellite content 14 days after VML to a level consistent with an endogenously healing ischemia-reperfusion induced Muscle injury. Moreover, regional analysis revealed that the combination therapy increased satellite cell density mostly in the remaining musculature, as opposed to the defect area. Based on the results, the following salient conclusions were drawn: 1) functional recovery mediated by the combination therapy is likely due to a superposition of de novo Muscle fiber regeneration and augmented repair of Muscle fibers within the remaining musculature, and 2) The capacity for VML therapies to augment regeneration and repair within the remaining musculature may have significant clinical impact and warrants further exploration.
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co delivery of micronized urinary bladder matrix damps regenerative capacity of minced Muscle Grafts in the treatment of volumetric Muscle loss injuries
PLOS ONE, 2017Co-Authors: Stephen M. Goldman, Benjamin T. CoronaAbstract:: Minced Muscle Grafts (MG) promote de novo Muscle fiber regeneration and neuromuscular strength recovery in small and large animal models of volumetric Muscle loss. The most noteworthy limitation of this approach is its reliance on a finite supply of donor tissue. To address this shortcoming, this study sought to evaluate micronized acellular urinary bladder matrix (UBM) as a scaffolding to promote in vivo expansion of this MG therapy in a rat model. Rats received volumetric Muscle loss injuries to the tibialis anterior Muscle of their left hind limb which were either left untreated or repaired with minced Muscle Graft at dosages of 50% and 100% of the defect mass, urinary bladder matrix in isolation, or a with an expansion product consisting of a combination of the two putative therapies in which the minced Graft is delivered at a dosage of 50% of the defect mass. Rats survived to 2 and 8 weeks post injury before functional (in vivo neuromuscular strength), histological, morphological, and biochemical analyses were performed. Rats treated with the expansion product exhibited improved neuromuscular function relative to untreated VML after an 8 week time period following injury. This improvement in functional capacity, however, was accompanied with a concomitant reduction in Graft mediated regeneration, as evidenced cell lineage tracing enable by a transgenic GFP expressing donor, and a mixed histological outcome indicating coincident fibrous matrix deposition with interspersed islands of nascent Muscle fibers. Furthermore, quantitative immunofluorescence and transcriptional analysis following the 2 week time point suggests an exacerbated immune response to the UBM as a possible nidus for the observed suboptimal regenerative outcome. Moving forward, efforts related to the development of a MG expansion product should carefully consider the effects of the host immune response to candidate biomaterials in order to avoid undesirable dysregulation of pro-regenerative cross talk between the immune system and myogenic processes.
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contribution of minced Muscle Graft progenitor cells to Muscle fiber formation after volumetric Muscle loss injury in wild type and immune deficient mice
Physiological Reports, 2017Co-Authors: Benjamin T. Corona, Beth E. P. Henderson, Catherine L Ward, Sarah M GreisingAbstract:Volumetric Muscle injury (VML) causes an irrecoverable loss of Muscle fibers, persistent strength deficits, and chronic disability. A crucial challenge to VML injury and possible regeneration is the removal of all of the in situ native elements necessary for skeletal Muscle regeneration. Our first goal was to establish a reliable VML model in the mouse tibialis anterior (TA) Muscle. In adult male wild‐type and nude mice, a non‐repaired ≈20% VML injury to the TA Muscle resulted in an ≈59% loss in nerve evoked Muscle strength, ≈33% loss in Muscle mass, and ≈29% loss of Muscle fibers at 28 day post‐injury. Our second goal was to investigate if minced Muscle Grafts (≈1 mm3 tissue fragments) promote recovery of Muscle fibers after VML injury and to understand if the Graft‐derived progenitor cells directly contribute to fiber regeneration. To assess donor cell contribution, donor Muscle tissue was derived from UBC‐GFP mice in a subset of experiments. Minced Grafts restored ≈34% of the lost fibers 28 days post‐injury. The number of GFP+ fibers and the estimated number of regenerated fibers were similar, regardless of host mouse strain. The Muscle tissue regeneration promoted by minced Grafts did not improve TA Muscle strength at this time post‐injury. These findings demonstrate the direct contribution of minced Muscle Graft‐derived myogenic stem/progenitor cells to recovery of Muscle fibers after VML injury and signify the utility of autologous myogenic stem cell therapies for this indication.
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Tacrolimus as an adjunct to autologous minced Muscle Grafts for the repair of a volumetric Muscle loss injury
SpringerOpen, 2017Co-Authors: Benjamin T. Corona, Jessica C. Rivera, Joseph C. Wenke, Sarah M GreisingAbstract:Abstract Background Volumetric Muscle loss (VML) following extremity orthopaedic trauma or surgery results in chronic functional deficits and disability. A current translational approach to address the devastating functional limitations due to VML injury is the use of an autologous minced Muscle Graft (~1 mm3 pieces of Muscle tissue) replacement into the injured defect area, although limitations related to donor site morbidity are still unaddressed. This study was designed to explore adjunct pharmacological immunomodulation to enhance Graft efficacy and promote Muscle function following VML injury, and thereby reduce the amount of donor tissue required. Findings Using a validated VML porcine injury model in which 20% of the Muscle volume was surgically removed, this study examined Muscle function over 3 months post-VML injury. In vivo isometric torque of the peroneus teritus (PT) Muscle was not different before surgery among sham, non-repaired, non-repaired with tacrolimus, Graft-repaired, and Graft-repaired with tacrolimus VML groups. Bi-weekly torque analysis of the VML injured musculature presented a significant strength deficit of ~26% compared to pre-injury in the non-repaired, non-repaired with tacrolimus, and Graft-repaired groups. Comparatively, the strength deficit in the Graft-repair with systemic tacrolimus was marginally improved (~19%; p = 0.056). Both of the minced Graft repaired groups presented a greater proportion of Muscle tissue in full-thickness histology specimen. Conclusions We demonstrate that adjunctive use of tacrolimus with an ~50% minced Muscle Graft replacement resulted in modest improvements in Muscle function 3 months after injury and repair, but the magnitude of improvement is not expected to elicit clinically meaningful functional improvements
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autologous minced Muscle Grafts a tissue engineering therapy for the volumetric loss of skeletal Muscle
American Journal of Physiology-cell Physiology, 2013Co-Authors: Benjamin T. Corona, Thomas J. Walters, Catherine L Ward, Koyal Garg, Jennifer S Mcdaniel, Christopher R RathboneAbstract:Volumetric Muscle loss (VML) results in a large void deficient in the requisite materials for regeneration for which there is no definitive clinical standard of care. Autologous minced Muscle Graft...
Lisa M Larkin - One of the best experts on this subject based on the ideXlab platform.
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engineered skeletal Muscle units for repair of volumetric Muscle loss in the tibialis anterior Muscle of a rat
Tissue Engineering Part A, 2014Co-Authors: Keith W Vandusen, Brian C Syverud, Michael L Williams, Lisa M LarkinAbstract:Volumetric Muscle loss (VML) is the traumatic, degenerative, or surgical loss of Muscle tissue, which may result in function loss and physical deformity. To date, clinical treatments for VML—the reflected Muscle flap or transferred Muscle Graft—are limited by tissue availability and donor site morbidity. To address the need for more innovative skeletal Muscle repair options, our laboratory has developed scaffoldless tissue-engineered skeletal Muscle units (SMUs), multiphasic tissue constructs composed of engineered skeletal Muscle with engineered bone-tendon ends, myotendinous junctions, and entheses, which in vitro can produce force both spontaneously and in response to electrical stimulation. Though phenotypically immature in vitro, we have shown that following 1 week of implantation in an ectopic site, our Muscle constructs develop vascularization and innervation, an epimysium-like outer layer of connective tissue, an increase in myosin protein content, formation of myofibers, and increased force production. These findings suggest that our engineered Muscle tissue survives implantation and develops the interfaces necessary to advance the phenotype toward adult Muscle. The purpose of this study was to evaluate the potential of our SMUs to restore Muscle tissue to sites of acute VML. Our results indicate that our SMUs continue to mature in vivo with longer recovery times and have the potential to repair VML sites by providing additional Muscle fibers to damaged Muscles. We conclude from this study that our SMUs have the potential to restore lost tissue volume in cases of acute VML.
Christopher R Rathbone - One of the best experts on this subject based on the ideXlab platform.
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autologous minced Muscle Grafts a tissue engineering therapy for the volumetric loss of skeletal Muscle
American Journal of Physiology-cell Physiology, 2013Co-Authors: Benjamin T. Corona, Thomas J. Walters, Catherine L Ward, Koyal Garg, Jennifer S Mcdaniel, Christopher R RathboneAbstract:Volumetric Muscle loss (VML) results in a large void deficient in the requisite materials for regeneration for which there is no definitive clinical standard of care. Autologous minced Muscle Graft...
Paul S Cederna - One of the best experts on this subject based on the ideXlab platform.
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regenerative peripheral nerve interface free Muscle Graft mass and function
Muscle & Nerve, 2021Co-Authors: Daniel C Ursu, Theodore A Kung, Racquel A Sohasky, Ian C Sando, Shoshana W Ambani, Zachary P French, Elizabeth A Mays, Andrej Nedic, Jana D Moon, Paul S CedernaAbstract:Background Regenerative peripheral nerve interfaces (RPNIs) transduce neural signals to provide high-fidelity control of neuroprosthetic devices. Traditionally, rat RPNIs are constructed with ~150 mg of free skeletal Muscle Grafts. It is unknown whether larger free Muscle Grafts allow RPNIs to transduce greater signal. Methods RPNIs were constructed by securing skeletal Muscle Grafts of various masses (150, 300, 600, or 1200 mg) to the divided peroneal nerve. In the control group, the peroneal nerve was transected without repair. Endpoint assessments were conducted 3 mo postoperatively. Results Compound Muscle action potentials (CMAPs), maximum tetanic isometric force, and specific Muscle force were significantly higher for both the 150 and 300 mg RPNI groups compared to the 600 and 1200 mg RPNIs. Larger RPNI Muscle groups contained central areas lacking regenerated Muscle fibers. Conclusions Electrical signaling and tissue viability are optimal in smaller as opposed to larger RPNI constructs in a rat model.
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chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque
Journal of Neural Engineering, 2016Co-Authors: Zachary T Irwin, Ian C Sando, Paul S Cederna, Karen E Schroeder, Derek M Tat, Autumn J Bullard, Shoshana L Woo, Melanie G Urbanchek, Cynthia A ChestekAbstract:Objective Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach The RPNI consists of a small, autologous partial Muscle Graft reinnervated by a transected peripheral nerve branch. After reinnervation, the Graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey's finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.
Stephen M. Goldman - One of the best experts on this subject based on the ideXlab platform.
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Co-delivery of a laminin-111 supplemented hyaluronic acid based hydrogel with minced Muscle Graft in the treatment of volumetric Muscle loss injury.
PloS one, 2018Co-Authors: Stephen M. Goldman, Beth E. P. Henderson, Thomas J. Walters, Benjamin T. CoronaAbstract:Minced Muscle autoGrafting mediates de novo myofiber regeneration and promotes partial recovery of neuromuscular strength after volumetric Muscle loss injury (VML). A major limitation of this approach is the availability of sufficient donor tissue for the treatment of relatively large VMLs without inducing donor site morbidity. This study evaluated a laminin-111 supplemented hyaluronic acid based hydrogel (HA+LMN) as a putative myoconductive scaffolding to be co-delivered with minced Muscle Grafts. In a rat tibialis anterior Muscle VML model, delivery of a reduced dose of minced Muscle Graft (50% of VML defect) within HA+LMN resulted in a 42% improvement of peak tetanic torque production over unrepaired VML affected limbs. However, the improvement in strength was not improved compared to a 50% minced Graft-only control group. Moreover, histological analysis revealed that the improvement in in vivo functional capacity mediated by minced Grafts in HA+LMN was not accompanied by a particularly robust Graft mediated regenerative response as determined through donor cell tracking of the GFP+ Grafting material. Characterization of the spatial distribution and density of macrophage and satellite cell populations indicated that the combination therapy damps the heightened macrophage response while re-establishing satellite content 14 days after VML to a level consistent with an endogenously healing ischemia-reperfusion induced Muscle injury. Moreover, regional analysis revealed that the combination therapy increased satellite cell density mostly in the remaining musculature, as opposed to the defect area. Based on the results, the following salient conclusions were drawn: 1) functional recovery mediated by the combination therapy is likely due to a superposition of de novo Muscle fiber regeneration and augmented repair of Muscle fibers within the remaining musculature, and 2) The capacity for VML therapies to augment regeneration and repair within the remaining musculature may have significant clinical impact and warrants further exploration.
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co delivery of micronized urinary bladder matrix damps regenerative capacity of minced Muscle Grafts in the treatment of volumetric Muscle loss injuries
PLOS ONE, 2017Co-Authors: Stephen M. Goldman, Benjamin T. CoronaAbstract:: Minced Muscle Grafts (MG) promote de novo Muscle fiber regeneration and neuromuscular strength recovery in small and large animal models of volumetric Muscle loss. The most noteworthy limitation of this approach is its reliance on a finite supply of donor tissue. To address this shortcoming, this study sought to evaluate micronized acellular urinary bladder matrix (UBM) as a scaffolding to promote in vivo expansion of this MG therapy in a rat model. Rats received volumetric Muscle loss injuries to the tibialis anterior Muscle of their left hind limb which were either left untreated or repaired with minced Muscle Graft at dosages of 50% and 100% of the defect mass, urinary bladder matrix in isolation, or a with an expansion product consisting of a combination of the two putative therapies in which the minced Graft is delivered at a dosage of 50% of the defect mass. Rats survived to 2 and 8 weeks post injury before functional (in vivo neuromuscular strength), histological, morphological, and biochemical analyses were performed. Rats treated with the expansion product exhibited improved neuromuscular function relative to untreated VML after an 8 week time period following injury. This improvement in functional capacity, however, was accompanied with a concomitant reduction in Graft mediated regeneration, as evidenced cell lineage tracing enable by a transgenic GFP expressing donor, and a mixed histological outcome indicating coincident fibrous matrix deposition with interspersed islands of nascent Muscle fibers. Furthermore, quantitative immunofluorescence and transcriptional analysis following the 2 week time point suggests an exacerbated immune response to the UBM as a possible nidus for the observed suboptimal regenerative outcome. Moving forward, efforts related to the development of a MG expansion product should carefully consider the effects of the host immune response to candidate biomaterials in order to avoid undesirable dysregulation of pro-regenerative cross talk between the immune system and myogenic processes.
