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Harnessing the synergy of perfusable muscle flap matrix and adipose-derived stem cells for prevascularization and macrophage polarization to reconstruct volumetric muscle loss

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Bioactive Materials 2023年第4期22卷 588-614页

作者： Qixu Zhang Yulun Chiu Youbai Chen Yewen Wu Lina W.Dunne Rene D.Largo Edward I.Chang David M.Adelman Mark V.Schaverien Charles E.Butler Department of Plastic Surgery The University of Texas MD Anderson Cancer CenterHoustonTX77030USA Department of Melanoma Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTX77030USA Department of Plastic Surgery Chinese PLA General HospitalBeijing100853China

muscle flaps must have a strong vascular network to support a large tissue volume and ensure successful *** developed porcine stomach musculofascial flap matrix(PDSF)comprising extracellular matrix(ECM)and intact *** had a dominant vascular pedicle,microcirculatory vessels,a nerve network,well-retained 3-dimensional(3D)nanofibrous ECM structures,and no allo-or ***-depth proteomic analysis demonstrated that PDSF was composed of core matrisome proteins(e.g.,collagens,glycoproteins,proteoglycans,and ECM regulators)that,as shown by Gene Ontology term enrichment analysis,are functionally related to musculofascial biological ***,PDSF􀀀human adipose-derived stem cell(hASC)synergy not only induced monocytes towards IL-10􀀀producing M2 macrophage polarization through the enhancement of hASCs’paracrine effect but also promoted the proliferation and interconnection of both human skeletal muscle myoblasts(HSMMs)and human umbilical vein endothelial cells(HUVECs)in static triculture ***,PDSF was successfully prevascularized through a dynamic perfusion coculture of hASCs and HUVECs,which integrated with PDSF and induced the maturation of vascular networks in *** a xenotransplantation model,PDSF demonstrated myoconductive and immunomodulatory properties associated with the predominance of M2 macrophages and regulatory T *** a volumetric muscle loss(VML)model,prevascularized PDSF augmented neovascularization and constructive remodeling,which was characterized by the predominant infiltration of M2 macrophages and significant musculofascial tissue *** results indicate that hASCs’integration with PDSF enhances the cells’dual function in immunomodulation and *** in part to this PDSF-hASC synergy,our platform shows promise for vascularized muscle flap engineering for VML reconstruction.

关键词： muscle flap fabrication Extracellular matrix Decellularization Vascularization Macrophage polarization volumetric muscle loss

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Biomimetic glycosaminoglycan-based scaffolds improve skeletal muscle regeneration in a Murine volumetric muscle loss model

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Bioactive Materials 2021年第4期6卷 1201-1213页

作者： Naagarajan Narayanan Zhihao Jia Kun Ho Kim Liangju Kuang Paul Lengemann Gabrielle Shafer Victor Bernal-Crespo Shihuan Kuang Meng Deng Department of Agricultural and Biological Engineering Purdue UniversityWest LafayetteIN47906United States Bindley Bioscience Center Purdue UniversityWest LafayetteIN47906United States Department of Animal Science Purdue UniversityWest LafayetteIN47906United States Center for Comparative Translational Research Purdue UniversityWest LafayetteIN47906United States School of Materials Engineering Purdue UniversityWest LafayetteIN47906United States Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteIN47906United States

volumetric muscle loss(VML)injuries characterized by critical loss of skeletal muscle tissues result in severe functional *** treatments involving use of muscle grafts are limited by tissue availability and donor site *** this study,we designed and synthesized an implantable glycosaminoglycan-based hydrogel system consisting of thiolated hyaluronic acid(HA)and thiolated chondroitin sulfate(CS)cross-linked with poly(ethylene glycol)diacrylate to promote skeletal muscle regeneration of VML injuries in *** HA-CS hydrogels were optimized with suitable biophysical properties by fine-tuning degree of thiol group substitution to support C2C12 myoblast proliferation,myogenic differentiation and expression of myogenic markers MyoD,MyoG and ***,in vivo studies using a murine quadriceps VML model demonstrated that the HA-CS hydrogels supported integration of implants with the surrounding host tissue and facilitated migration of Pax7+satellite cells,de novo myofiber formation,angiogenesis,and innervation with minimized scar tissue formation during 4-week *** hydrogel-treated and autograft-treated mice showed similar functional improvements in treadmill performance as early as 1-week post-implantation compared to the untreated *** together,our results demonstrate the promise of HA-CS hydrogels as regenerative engineering matrices to accelerate healing of skeletal muscle injuries.

关键词： Hyaluronic acid Chondroitin sulfate Hydrogels volumetric muscle loss Myoblasts Skeletal muscle tissue engineering

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Scaffold tissue engineering strategies for volumetric muscle loss

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Plastic and Aesthetic Research 2023年第1期10卷 96-112页

作者： Christina Zhu Karina Sklyar Mehran Karvar Yori Endo Indranil Sinha Division of Plastic Surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Texas Tech University Health Sciences Center School of Medicine LubbockTX 79430USA

volumetric muscle loss(VML)refers to a composite,en bloc loss of skeletal muscle mass resulting in functional *** injuries normally heal with excessive fibrosis,minimal skeletal muscle regeneration,and poor functional *** muscle transfer is a treatment option for some patients but is limited both by the degree of functional restoration as well as donor site *** such,new therapeutic options are *** novo regeneration of skeletal muscle,by way of tissue engineering,is an emerging strategy to treat *** review evaluates available scaffolds for promoting skeletal muscle regeneration and functional recovery following *** use of growth factors and stem cell therapies,which may augment scaffold integration and skeletal muscle reconstitution,are also *** medicine with the use of scaffolds is a promising area in skeletal muscle reconstruction and VML treatment.

关键词： volumetric muscle loss tissue engineering scaffolds skeletal muscle regeneration

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In vivo measurement of NADH fluorescence lifetime in skeletal muscle via -ber-coupled time-correlated single photon counting

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 121-134页

作者： Kathryn M.Priest Jacob V.Schluns Nathania Nischal Colton L.Gattis Jeffrey C.Wolchok Timothy J.Muldoon Department of Biomedical Engineering University of Arkansas FayettevilleARUSA

Nicotinamide adenine dinucleotide(NADH)is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis,the tricarboxylic acid cycle,and oxidative phosphorylation(OXPHOS).NADH is autofluorescent,and itsfluorescence lifetime can be used to infer metabolic dynamics in living ***-coupled time-correlated single photon counting(TCSPC)equipped with an implantable needle probe can be used to measure NADH lifetime in vivo,enabling investigation of changing metabolic demand during muscle contraction or tissue *** study illustrates a proof of concept for point-based,minimally-invasive NADHfluorescence lifetime measurement in *** muscle loss(VML)injuries were created in the left tibialis anterior(TA)muscle of male Sprague Dawley *** lifetime measurements were collected before,during,and after a 30 s tetanic contraction in the injured and uninjured TA muscles,which was subsequently-t to a biexponential decay model to yield a metric of NADH utilization(cytoplasmic vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after contraction in uninjured muscle compared to muscle at rest,suggesting higher levels of free NADH in contracting and recovering muscle,indicating increased rates of *** injured muscle,this ratio was higher than uninjured muscle overall but decreased over time,which is consistent with current knowledge of inflammatory response to injury,suggesting tissue regeneration has *** data suggest that-ber-coupled TCSPC has the potential to measure changes in NADH binding in vivo in a minimally invasive manner that requires further investigation.

关键词： Glycolysis oxidative phosphorylation energy metabolism volumetric muscle loss

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