scholarly journals Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss

2020 ◽  
Vol 7 (3) ◽  
pp. 85 ◽  
Author(s):  
Meagan E. Carnes ◽  
George D. Pins
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Scar Tissue ◽  
Tissue Loss ◽  
Direct Regeneration ◽  
Small Scale ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss

Millions of Americans suffer from skeletal muscle injuries annually that can result in volumetric muscle loss (VML), where extensive musculoskeletal damage and tissue loss result in permanent functional deficits. In the case of small-scale injury skeletal muscle is capable of endogenous regeneration through activation of resident satellite cells (SCs). However, this is greatly reduced in VML injuries, which remove native biophysical and biochemical signaling cues and hinder the damaged tissue’s ability to direct regeneration. The current clinical treatment for VML is autologous tissue transfer, but graft failure and scar tissue formation leave patients with limited functional recovery. Tissue engineering of instructive biomaterial scaffolds offers a promising approach for treating VML injuries. Herein, we review the strategic engineering of biophysical and biochemical cues in current scaffold designs that aid in restoring function to these preclinical VML injuries. We also discuss the successes and limitations of the three main biomaterial-based strategies to treat VML injuries: acellular scaffolds, cell-delivery scaffolds, and in vitro tissue engineered constructs. Finally, we examine several innovative approaches to enhancing the design of the next generation of engineered scaffolds to improve the functional regeneration of skeletal muscle following VML injuries.

scholarly journals Applications of Small Molecules in Muscle Tissue Engineering

2021 ◽  
Author(s):  
Behnaz Mirza Ahmadi ◽  
Mahmood Talkhabi ◽  
Sarah Rajabi
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Small Molecules ◽  
Muscle Tissue ◽  
Muscle Regeneration ◽  
Cost Effective ◽  
Clinical Approach ◽  
Muscle Injuries ◽  
Inducing Factors

Introduction: Skeletal muscles account for about 40% of the total body weight. Every year, hundreds of people lose at least part of their muscle tissue due to illness, war, and accidents. This can lead to disruption of activities such as breathing, movement, and social life. To this end, various therapeutic strategies such as medication therapy, cell therapy and tissue transplantation have been used or studied in muscle regeneration. However, there is no effective and well-defined clinical approach for treatment of muscle injuries and the severity of muscle injuries increase with age in most cases. Therefore, investigation for finding new and effective clinical approach for muscle regeneration is one of the most important issues in basic and clinical researches. Tissue engineering is considered as one of the promising and newest approach for skeletal muscle tissue regeneration and provides an appropriate model for personalized medicine and basic researches that can be used in personalized medicine and basic research. Besides biomaterials and cells, inducing factors are another element of tissue engineering. These factors influence epigenetic mechanisms and signaling pathway, thereby inducing proliferation, differentiation, and migration of cells used in muscle tissue engineering, and accelerates muscle formation in vitro. Recently, small molecules have been used as alternatives to growth factors or along with other inducing factors in muscle tissue engineering. Since they do not induce an immune reaction, penetrate easily to the cells and have a specific molecular target, therefore they have attracted much attention as the cost-effective inducing factors in tissue engineering. Conclusion:  Taken together, the effective small molecules in muscle tissue engineering can be used with different biomaterial conditions (e.g. hydrogel, decellularized tissue, and synthetic scaffolds) in both in vivo and in vitro, resulting to production of cost effective and highly efficient engineered muscle tissues that help to achieve therapeutical goals of muscle tissue engineering. Herein, we describe tissue engineering and review the small molecules used in skeletal muscle tissue engineering.

Losartan administration reduces fibrosis but hinders functional recovery after volumetric muscle loss injury

2014 ◽  
Vol 117 (10) ◽  
pp. 1120-1131 ◽  
Author(s):  
Koyal Garg ◽  
Benjamin T. Corona ◽  
Thomas J. Walters
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Function ◽  
Collagen Type ◽  
Force Production ◽  
Collagen Type I ◽  
Type I ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss

Losartan is a Food and Drug Administration approved antihypertensive medication that is recently emerging as an antifibrotic therapy. Previously, losartan has been successfully used to reduce fibrosis and improve both muscle regeneration and function in several models of recoverable skeletal muscle injuries, such as contusion and laceration. In this study, the efficacy of losartan treatment in reducing fibrosis and improving regeneration was determined in a Lewis rat model of volumetric muscle loss (VML) injury. VML has been defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. It is among the top 10 causes for wounded service members to be medically retired from the military. This study shows that, after several weeks of recovery, VML injury results in little to no muscle regeneration, but is marked by persistent inflammation, chronic upregulation of profibrotic markers and extracellular matrix (i.e., collagen type I), and fat deposition at the defect site, which manifest irrecoverable deficits in force production. Losartan administration at 10 mg·kg−1·day−1was able to modulate the gene expression of fibrotic markers and was also effective at reducing fibrosis (i.e., the deposition of collagen type I) in the injured muscle. However, there were no improvements in muscle regeneration, and deleterious effects on muscle function were observed instead. We propose that, in the absence of regeneration, reduction in fibrosis worsens the ability of the VML injured muscle to transmit forces, which ultimately results in decreased muscle function.

scholarly journals Myogenic differentiation of human amniotic mesenchymal cells and its tissue repair capacity on volumetric muscle loss

2019 ◽  
Vol 10 ◽  
pp. 204173141988710 ◽  
Author(s):  
Di Zhang ◽  
Kai Yan ◽  
Jing Zhou ◽  
Tianpeng Xu ◽  
Menglei Xu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Stem Cell ◽  
Tissue Repair ◽  
Myogenic Differentiation ◽  
Embryonic Stem ◽  
Mesenchymal Cells ◽  
Muscle Loss ◽  
Repair Capacity ◽  
Volumetric Muscle Loss

Stem cell–based tissue engineering therapy is the most promising method for treating volumetric muscle loss. Human amniotic mesenchymal cells possess characteristics similar to those of embryonic stem cells. In this study, we verified the stem cell characteristics of human amniotic mesenchymal cells by the flow cytometry analysis, and osteogenic and adipogenic differentiation. Through induction with the DNA demethylating agent 5-azacytidine, human amniotic mesenchymal cells can undergo myogenic differentiation and express skeletal muscle cell–specific markers such as desmin and MyoD. The Wnt/β-catenin signaling pathway also plays an important role. After 5-azacytidine-induced human amniotic mesenchymal cells were implanted into rat tibialis anterior muscle with volumetric muscle loss, we observed increased angiogenesis and improved local tissue repair. We believe that human amniotic mesenchymal cells can serve as a potential source of cells for skeletal muscle tissue engineering.

The Potential of Combination Therapeutics for More Complete Repair of Volumetric Muscle Loss Injuries: The Role of Exogenous Growth Factors and/or Progenitor Cells in Implantable Skeletal Muscle Tissue Engineering Technologies

2016 ◽  
Vol 202 (3-4) ◽  
pp. 202-213 ◽  
Author(s):  
Juliana A. Passipieri ◽  
George J. Christ
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Growth Factors ◽  
Host Cell ◽  
Matrix Remodeling ◽  
Muscle Loss ◽  
Regenerative Capacity ◽  
Volumetric Muscle Loss ◽  
Exogenous Growth ◽  
Exogenous Growth Factors

Despite the robust regenerative capacity of skeletal muscle, there are a variety of congenital and acquired conditions in which the volume of skeletal muscle loss results in major permanent functional and cosmetic deficits. These latter injuries are referred to as volumetric muscle loss (VML) injuries or VML-like conditions, and they are characterized by the simultaneous absence of multiple tissue components (i.e., nerves, vessels, muscles, satellite cells, and matrix). There are currently no effective treatment options. Regenerative medicine/tissue engineering technologies hold great potential for repair of these otherwise irrecoverable VML injuries. In this regard, three-dimensional scaffolds have been used to deliver sustained amounts of growth factors into a variety of injury models, to modulate host cell recruitment and extracellular matrix remodeling. However, this is a nascent field of research, and more complete functional improvements require more precise control of the spatiotemporal distribution of critical growth factors over a physiologically relevant range. This is especially true for VML injuries where incorporation of a cellular component into the scaffolds might provide not only a source of new tissue formation but also additional signals for host cell migration, recruitment, and survival. To this end, we review the major features of muscle repair and regeneration for largely recoverable injuries, and then discuss recent cell- and/or growth factor-based approaches to repair the more profound and irreversible VML and VML-like injuries. The underlying supposition is that more rationale incorporation of exogenous growth factors and/or cellular components will be required to optimize the regenerative capacity of implantable therapeutics for VML repair.

scholarly journals Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal muscle injuries

2015 ◽  
Vol 25 ◽  
pp. 2-15 ◽  
Author(s):  
Jonathan M. Grasman ◽  
Michelle J. Zayas ◽  
Raymond L. Page ◽  
George D. Pins
Keyword(s):  
Skeletal Muscle ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss ◽  
Biomimetic Scaffolds

scholarly journals Biofabricating murine and human myo-substitutes for rapid volumetric muscle loss restoration

2020 ◽  
Author(s):  
Marco Costantini ◽  
Stefano Testa ◽  
Ersilia Fornetti ◽  
Claudia Fuoco ◽  
Minghao Nie ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Neuromuscular Junctions ◽  
Tissue Loss ◽  
Solid Base ◽  
Large Animal ◽  
Muscle Loss ◽  
Volumetric Muscle Loss ◽  
Vital Functions ◽  
Clinical Scenarios

AbstractThe importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo-substitutes support the formation of new blood vessels and neuromuscular junctions – pivotal aspects for cell survival and muscle contractile functionalities – together with an advanced along with muscle mass and force recovery. Together, these data represent a solid base for further testing the myo-substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.

scholarly journals Immunomodulation and Biomaterials: Key Players to Repair Volumetric Muscle Loss

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2016
Author(s):  
Sonia Kiran ◽  
Pankaj Dwivedi ◽  
Vijay Kumar ◽  
Robert L. Price ◽  
Udai P. Singh
Keyword(s):  
Skeletal Muscle ◽  
Immune Response ◽  
Inflammatory Response ◽  
Muscle Injury ◽  
Regenerative Process ◽  
Great Promise ◽  
Muscle Loss ◽  
Muscle Injuries ◽  
Volumetric Muscle Loss ◽  
Challenging Situation

Volumetric muscle loss (VML) is defined as a condition in which a large volume of skeletal muscle is lost due to physical insult. VML often results in a heightened immune response, resulting in significant long-term functional impairment. Estimates indicate that ~250,000 fractures occur in the US alone that involve VML. Currently, there is no active treatment to fully recover or repair muscle loss in VML patients. The health economics burden due to VML is rapidly increasing around the world. Immunologists, developmental biologists, and muscle pathophysiologists are exploring both immune responses and biomaterials to meet this challenging situation. The inflammatory response in muscle injury involves a non-specific inflammatory response at the injured site that is coordination between the immune system, especially macrophages and muscle. The potential role of biomaterials in the regenerative process of skeletal muscle injury is currently an important topic. To this end, cell therapy holds great promise for the regeneration of damaged muscle following VML. However, the delivery of cells into the injured muscle site poses a major challenge as it might cause an adverse immune response or inflammation. To overcome this obstacle, in recent years various biomaterials with diverse physical and chemical nature have been developed and verified for the treatment of various muscle injuries. These biomaterials, with desired tunable physicochemical properties, can be used in combination with stem cells and growth factors to repair VML. In the current review, we focus on how various immune cells, in conjunction with biomaterials, can be used to promote muscle regeneration and, most importantly, suppress VML pathology.

scholarly journals Regenerative medicine for skeletal muscle loss: a review of current tissue engineering approaches

2021 ◽  
Vol 32 (1) ◽  
Author(s):  
Benjamin Langridge ◽  
Michelle Griffin ◽  
Peter E. Butler
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
Current Status ◽  
Surgical Approaches ◽  
Muscle Loss ◽  
Functional Maturation

AbstractSkeletal muscle is capable of regeneration following minor damage, more significant volumetric muscle loss (VML) however results in permanent functional impairment. Current multimodal treatment methodologies yield variable functional recovery, with reconstructive surgical approaches restricted by limited donor tissue and significant donor morbidity. Tissue-engineered skeletal muscle constructs promise the potential to revolutionise the treatment of VML through the regeneration of functional skeletal muscle. Herein, we review the current status of tissue engineering approaches to VML; firstly the design of biocompatible tissue scaffolds, including recent developments with electroconductive materials. Secondly, we review the progenitor cell populations used to seed scaffolds and their relative merits. Thirdly we review in vitro methods of scaffold functional maturation including the use of three-dimensional bioprinting and bioreactors. Finally, we discuss the technical, regulatory and ethical barriers to clinical translation of this technology. Despite significant advances in areas, such as electroactive scaffolds and three-dimensional bioprinting, along with several promising in vivo studies, there remain multiple technical hurdles before translation into clinically impactful therapies can be achieved. Novel strategies for graft vascularisation, and in vitro functional maturation will be of particular importance in order to develop tissue-engineered constructs capable of significant clinical impact.

Mechanical and Electrical Stimulation Induces Calcium-Sensitive Mechanical Properties of Myoblast Derived Engineered Fibers

2013 ◽  
Author(s):  
Andrew K. Mason ◽  
Ryan A. Koppes ◽  
Douglas M. Swank ◽  
David T. Corr
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Donor Site ◽  
Tissue Loss ◽  
Muscle Loss ◽  
Autologous Tissue ◽  
Skeletal Muscle Loss ◽  
Autologous Grafts ◽  
Interventional Medicine

Skeletal muscle loss, through injuries, myopathies, and interventional medicine, presents major challenges in physiological function and clinical interventions [1]. Autologous tissue transplantation necessitates tissue loss from the donor site, and autologous grafts do not attain the strength of the original tissue. Exogenous tissue grafting faces similar strength issues, as well as the added challenge of immunorejection [2,3]. In vitro skeletal muscle tissue engineering holds promise for addressing these issues. However, these tissues have not yet shown proper dynamic response when compared to physiological muscle [2]. Mechanical and electrical stimulation have shown promise in improving construct properties [4], but mainly limited to 2D and scaffold-based constructs.

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