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Advanced Healthcare Materials Jan 2020Volumetric muscle loss (VML) is a devastating loss of muscle tissue that overwhelms the native regenerative properties of skeletal muscle and results in lifelong... (Review)
Review
Volumetric muscle loss (VML) is a devastating loss of muscle tissue that overwhelms the native regenerative properties of skeletal muscle and results in lifelong functional deficits. There are currently no treatments for VML that fully recover the lost muscle tissue and function. Tissue engineering presents a promising solution for VML treatment and significant research has been performed using tissue engineered muscle constructs in preclinical models of VML with a broad range of defect locations and sizes, tissue engineered construct characteristics, and outcome measures. Due to the complex vascular and neural anatomy within skeletal muscle, regeneration of functional vasculature and nerves is vital for muscle recovery following VML injuries. This review aims to summarize the current state of the field of skeletal muscle tissue engineering using 3D constructs for VML treatment with a focus on studies that have promoted vascular and neural regeneration within the muscle tissue post-VML.
Topics: Animals; Blood Vessels; Humans; Hydrogels; Muscle, Skeletal; Muscular Diseases; Regeneration; Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 31622051
DOI: 10.1002/adhm.201900626 -
Advanced Materials (Deerfield Beach,... Mar 2022Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current... (Review)
Review
Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current treatments result in variable functional recovery, while reconstructive surgery, as the gold-standard approach, is limited due to donor shortage, donor-site morbidity, and limited functional recovery. Skeletal muscle tissue engineering (SMTE) has generated enthusiasm as an alternative solution for treatment of injured tissue and serves as a functional disease model. Recently, bioprinting has emerged as a promising tool for recapitulating the complex and highly organized architecture of skeletal muscles at clinically relevant sizes. Here, skeletal muscle physiology, muscle regeneration following injury, and current treatments following muscle loss are discussed, and then bioprinting strategies implemented for SMTE are critically reviewed. Subsequently, recent advancements that have led to improvement of bioprinting strategies to construct large muscle structures, boost myogenesis in vitro and in vivo, and enhance tissue integration are discussed. Bioinks for muscle bioprinting, as an essential part of any bioprinting strategy, are discussed, and their benefits, limitations, and areas to be improved are highlighted. Finally, the directions the field should expand to make bioprinting strategies more translational and overcome the clinical unmet needs are discussed.
Topics: Bioprinting; Muscle, Skeletal; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds
PubMed: 34773667
DOI: 10.1002/adma.202105883 -
International Journal of Molecular... Dec 2020There has been an escalation in reports over the last decade examining the efficacy of bone marrow derived mesenchymal stem/stromal cells (BMSC) in bone tissue... (Review)
Review
There has been an escalation in reports over the last decade examining the efficacy of bone marrow derived mesenchymal stem/stromal cells (BMSC) in bone tissue engineering and regenerative medicine-based applications. The multipotent differentiation potential, myelosupportive capacity, anti-inflammatory and immune-modulatory properties of BMSC underpins their versatile nature as therapeutic agents. This review addresses the current limitations and challenges of exogenous autologous and allogeneic BMSC based regenerative skeletal therapies in combination with bioactive molecules, cellular derivatives, genetic manipulation, biocompatible hydrogels, solid and composite scaffolds. The review highlights the current approaches and recent developments in utilizing endogenous BMSC activation or exogenous BMSC for the repair of long bone and vertebrae fractures due to osteoporosis or trauma. Current advances employing BMSC based therapies for bone regeneration of craniofacial defects is also discussed. Moreover, this review discusses the latest developments utilizing BMSC therapies in the preclinical and clinical settings, including the treatment of bone related diseases such as Osteogenesis Imperfecta.
Topics: Animals; Humans; Mesenchymal Stem Cells; Muscle, Skeletal; Regeneration; Tissue Engineering
PubMed: 33371306
DOI: 10.3390/ijms21249759 -
Cell Reports Apr 2018Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D)...
Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development.
Topics: Cell Differentiation; Cell Lineage; Humans; Hydrogels; Induced Pluripotent Stem Cells; Models, Biological; Muscle Development; Muscle, Skeletal; Muscular Dystrophies; Tissue Engineering; Tissue Scaffolds
PubMed: 29669293
DOI: 10.1016/j.celrep.2018.03.091 -
Biofabrication Sep 2022Bioengineered human skeletal muscle tissues have emerged in the last years as newsystems for disease modeling. These bioartificial muscles are classically fabricated by...
Bioengineered human skeletal muscle tissues have emerged in the last years as newsystems for disease modeling. These bioartificial muscles are classically fabricated by encapsulating human myogenic precursor cells in a hydrogel scaffold that resembles the extracellular matrix. However, most of these hydrogels are derived from xenogenic sources, and the culture media is supplemented with animal serum, which could interfere in drug testing assays. On the contrary, xeno-free biomaterials and culture conditions in tissue engineering offer increased relevance for developing human disease models. In this work, we used human platelet lysate (PL)-based nanocomposite hydrogels (HUgel) as scaffolds for human skeletal muscle tissue engineering. These hydrogels consist of human PL reinforced with aldehyde-cellulose nanocrystals (a-CNC) that allow tunable mechanical, structural, and biochemical properties for the 3D culture of stem cells. Here, we developed hydrogel casting platforms to encapsulate human muscle satellite stem cells in HUgel. The a-CNC content was modulated to enhance matrix remodeling, uniaxial tension, and self-organization of the cells, resulting in the formation of highly aligned, long myotubes expressing sarcomeric proteins. Moreover, the bioengineered human muscles were subjected to electrical stimulation, and the exerted contractile forces were measured in a non-invasive manner. Overall, our results demonstrated that the bioengineered human skeletal muscles could be built in xeno-free cell culture platforms to assess tissue functionality, which is promising for drug development applications.
Topics: Animals; Extracellular Matrix; Humans; Hydrogels; Muscle Development; Muscle, Skeletal; Tissue Engineering; Tissue Scaffolds
PubMed: 36041422
DOI: 10.1088/1758-5090/ac8dc8 -
BioMed Research International 2018Skeletal muscle has the capacity of regeneration after injury. However, for large volumes of muscle loss, this regeneration needs interventional support. Consequently,... (Review)
Review
Skeletal muscle has the capacity of regeneration after injury. However, for large volumes of muscle loss, this regeneration needs interventional support. Consequently, muscle injury provides an ongoing reconstructive and regenerative challenge in clinical work. To promote muscle repair and regeneration, different strategies have been developed within the last century and especially during the last few decades, including surgical techniques, physical therapy, biomaterials, and muscular tissue engineering as well as cell therapy. Still, there is a great need to develop new methods and materials, which promote skeletal muscle repair and functional regeneration. In this review, we give a comprehensive overview over the epidemiology of muscle tissue loss, highlight current strategies in clinical treatment, and discuss novel methods for muscle regeneration and challenges for their future clinical translation.
Topics: Animals; Humans; Muscle, Skeletal; Regeneration; Tissue Engineering
PubMed: 29850487
DOI: 10.1155/2018/1984879 -
Journal of Applied Physiology... Oct 2021The purpose of this project was to provide a profile of DNA, RNA, and protein content in adipose tissue, which is relatively understudied in humans, to gain more insight...
The purpose of this project was to provide a profile of DNA, RNA, and protein content in adipose tissue, which is relatively understudied in humans, to gain more insight into the amount of tissue that may be required for various analyses. Skeletal muscle tissue was also investigated to provide a direct comparison into potential differences between these two highly metabolically active tissues. Basal adipose and skeletal muscle tissue samples were obtained from 10 (7 M, 3 W) recreationally active participants [25 ± 1 yr; 84 ± 3 kg, maximal oxygen consumption (V̇o): 3.5 ± 0.2 L/min, body fat: 29 ± 2%]. DNA, RNA, and protein were extracted and subsequently analyzed for quantity and quality. DNA content of adipose and skeletal muscle tissue was 52 ± 14 and 189 ± 44 ng DNA·mg tissue, respectively ( < 0.05). RNA content of adipose and skeletal muscle tissue was 46 ± 14 and 537 ± 72 ng RNA·mg tissue, respectively ( < 0.05). Protein content of adipose and skeletal muscle tissue was 4 ± 1 and 177 ± 10 µg protein·mg tissue, respectively ( < 0.05). In summary, human adipose had 28% of the DNA, 9% of the RNA, and 2% of the protein found in skeletal muscle per mg of tissue. This information should be useful across a wide range of human clinical investigation designs and various laboratory analyses. This investigation studied DNA, RNA, and protein contents of adipose and skeletal muscle tissues from young active individuals. A series of optimization steps were investigated to aid in determining the optimal approach to extract high-yield and high-quality biomolecules. These findings contribute to the knowledge gap in adipose tissue requirements for molecular biology assays, which is of increasing importance due to the growing interest in adipose tissue research involving human exercise physiology research.
Topics: Adipose Tissue; DNA; Exercise; Humans; Muscle, Skeletal; RNA
PubMed: 34435508
DOI: 10.1152/japplphysiol.00343.2021 -
Tissue Engineering. Part B, Reviews Oct 2014Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease.... (Review)
Review
Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.
Topics: Cell Differentiation; Coculture Techniques; Humans; Muscle Fibers, Skeletal; Myoblasts; Tissue Engineering
PubMed: 24320971
DOI: 10.1089/ten.TEB.2013.0534 -
Skeletal Muscle Feb 2020Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e., satellite cells, SCs), differentiated... (Review)
Review
Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e., satellite cells, SCs), differentiated cells (i.e., myofibers), and extracellular matrix cause a decline in tissue homeostasis, function, and regenerative capacity. Based on the conservation of aging across tissues and taking advantage of the relatively well-characterization of the myofibers and associated SCs, skeletal muscle emerged as an experimental system to study the decline in function and maintenance of old tissues and to explore rejuvenation strategies. In this review, we summarize the approaches for understanding the aging process and for assaying the success of rejuvenation that use skeletal muscle as the experimental system of choice. We further discuss (and exemplify with studies of skeletal muscle) how conflicting results might be due to variations in the techniques of stem cell isolation, differences in the assays of functional rejuvenation, or deciding on the numbers of replicates and experimental cohorts.
Topics: Aging; Animals; Cell Self Renewal; Humans; Muscle, Skeletal; Primary Cell Culture
PubMed: 32033591
DOI: 10.1186/s13395-020-0222-1 -
Advanced Materials (Deerfield Beach,... Dec 2016Repair of damaged skeletal-muscle tissue is limited by the regenerative capacity of the native tissue. Current clinical approaches are not optimal for the treatment of... (Review)
Review
Repair of damaged skeletal-muscle tissue is limited by the regenerative capacity of the native tissue. Current clinical approaches are not optimal for the treatment of large volumetric skeletal-muscle loss. As an alternative, tissue engineering represents a promising approach for the functional restoration of damaged muscle tissue. A typical tissue-engineering process involves the design and fabrication of a scaffold that closely mimics the native skeletal-muscle extracellular matrix (ECM), allowing organization of cells into a physiologically relevant 3D architecture. In particular, anisotropic materials that mimic the morphology of the native skeletal-muscle ECM, can be fabricated using various biocompatible materials to guide cell alignment, elongation, proliferation, and differentiation into myotubes. Here, an overview of fundamental concepts associated with muscle-tissue engineering and the current status of muscle-tissue-engineering approaches is provided. Recent advances in the development of anisotropic scaffolds with micro- or nanoscale features are reviewed, and how scaffold topographical, mechanical, and biochemical cues correlate to observed cellular function and phenotype development is examined. Finally, some recent developments in both the design and utility of anisotropic materials in skeletal-muscle-tissue engineering are highlighted, along with their potential impact on future research and clinical applications.
Topics: Animals; Biocompatible Materials; Cell Differentiation; Extracellular Matrix; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Tissue Engineering; Tissue Scaffolds
PubMed: 27865007
DOI: 10.1002/adma.201600240