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Muscle Engineering - New Organ Alliance

Muscle Engineering

The main focus area of this committee is addressing Muscle Wasting, i.e muscle atrophy or sarcopenia.

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Muscle engineering 
overview

Muscle wasting, an inevitable part of aging, is a chronic process resulting with loss of skeletal muscle mass and strength that occurs at varying kinetics of time and severity based on personalized medical conditions. It is a leading global public health concern with high impact on economic cost and quality of life: seniors at ages 65+ years currently compromise almost 15% of the US population and it is projected to grow in numbers at a rate of 56% to reach 2 billion globally by year 2050. Muscle wasting is also a critical concern for national security and the US military where mobilization and physical fitness is the essence for the recovery of a wounded warrior.

In addition, muscle wasting is also observed in populations with diabetes, cancer patients, and persons who have had heart conditions due to the decreased use of muscles. Currently, the treatment is confined to supportive measures including regular exercise and nutrition to slow or reverse the muscle atrophy, but these measures may offer limited help. Particularly in geriatric population, it is most rewarding if the onset of muscle atrophy is prolonged or delayed. Skeletal muscle tissue constitutes almost 50% of the total body weight. The committee will also focus on the interfacing of hybrid prosthetics for replacing lost musculoskeletal tissue by utilizing synthetic materials, robotics and automation such as emerging soft robotics, wearable robotic devices that may provide equal or enhances functional outcomes for improvement of physical capabilities as well as psychological well-being.

Knowledge Gap


A fundamental aspect of muscle tissue formation and repair is the cell fusion and re-organization of the cytoskeleton and subcellular components. In this committee, we will address the challenges associated with examining biophysical phenomena involved in cellular and subcellular component fusion and fission and their roles in modulation of molecular pathways that may eventually leading to muscle wasting, which will be then compared to cytoskeleton and sub cellular components reorganization and modulation of molecular pathways involved in muscle wasting under microgravity environment. The goal is to establish personalized tissue engineering strategies to address muscle wasting.

Causes of Muscle Wasting

Overarching Challenges in Muscle Engineering


Fundamental challenges remain in understanding the basic cellular and sub-cellular phenomenon that occur during muscle wasting. Knowledge of these phenomenon is required prior to being able to accurately engineer new muscles or muscle tissues for patients in need. These challenges include:

  • Lack of the availability of organized fundamental knowledge of muscle wasting at the sub-cellular level detailing the alteration of biophysical phenomena and alteration of associated molecular pathways to establish personalized tissue engineering strategies: Although muscle wasting is a complex health condition involving multifactorial and multi-systemic physiological inputs such as endocrine, cardiovascular, metabolic and inflammatory systems, our understanding of the very early phases of subcellular processes and associated molecular pathways in muscle wasting is limited. It is critical to identify personalized early stage biomarkers that are involved in muscle wasting to be able to design effective treatment protocols for improved outcomes.
  • There is limited evidence showing that the cell and subcellular component reorganization can occur due to specific muscle related diseases or injury. During aging or cachexia, there is decreased capacity of regeneration. Understanding the key parameters involved on aging related muscle wasting and developing tissue engineering strategies for reversing aging and enhance the regenerative ability of the muscle tissue. Age related cytoskeleton and sub cellular components such as mitochondria reorganization are essential, but there is only limited knowledge in this area.
  • Challenges and opportunities to shift current research or clinical practice paradigms by utilizing novel theoretical concepts and approaches/methodologies and instrumentation. Comprehensive analysis of cause and effect of muscle wasting is essential when finding solutions. Understanding the limitations of the existing treatment protocols and finding solutions to the technological and engineering gaps associated with muscle wasting. Identification signs of early stages of muscle wasting whether age related or trauma related or disease related and coming up with innovative solutions to address those early stage signs.
  • Muscle wasting occurs rapidly among astronauts during space flight. This is a reproducible phenomenon as shown in animal models ranging from fish to primates when exposed to microgravity. The underlying pathogenesis remains poorly understood since it was first observed about three decades ago. The pathology findings of muscle biopsies from four astronauts before and after their 17 days of NASA Life and Microgravity Spacelab (LMS) Space Shuttle mission in July 1996 are the direct and resourceful initial hard evidence on muscle wasting in microgravity. These included decreased muscle fiber size by light microscopy and decreased thin filaments by electron microscopy. There was no necrosis. It is important to note that the ultrastructural findings of increased lipid droplets, as well as, disorganized sarcomeric changes and inter-filamental holes found in these biopsies are still difficult to explain fully. There have been several studies investigating different aspects of muscle atrophy in microgravity but to our knowledge none have investigated early subcellular level changes in 3D tissue cultures. Therefore, performing a well-controlled study to examine the cytoskeleton and sub cellular components such as mitochondria reorganization and alteration of molecular pathways under microgravity environment is needed.
  • Comprehensive analysis of federally conducted regenerative medicine RDT&E pertaining to muscle wasting, which may include muscle stimulation or musculoskeletal replacing prosthetics. Identification of gaps and establish criteria and long term vision for application and product driven RDT&E for improvement of capabilities including hybrid prosthetics and tissues for optimized functional outcomes, This focus will cover the lost limbs or losing compartmentalized musculoskeletal segments.
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