scholarly journals 3D-printed drug testing platform based on a 3D model of aged human skeletal muscle

2020 ◽  
Author(s):  
Rafael Mestre ◽  
Nerea García ◽  
Tania Patiño ◽  
Maria Guix ◽  
Mauricio Valerio-Santiago ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Disease Modeling ◽  
Force Measurement ◽  
Muscle Relaxation ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Muscular Tissue ◽  
Functional Changes ◽  
3D Printed

AbstractThree-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modelling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aged or senescence-like tissue, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.

scholarly journals A three-dimensional culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction and disease modeling

2018 ◽  
Author(s):  
Mohsen Afshar Bakooshli ◽  
Ethan S Lippmann ◽  
Ben Mulcahy ◽  
Nisha R Iyer ◽  
Christine T Nguyen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Human Skeletal Muscle ◽  
Disease Modeling ◽  
De Novo ◽  
Muscle Fibers ◽  
Three Dimensional ◽  
Adult Human

SummaryTwo-dimensional (2D) human skeletal muscle fiber cultures are ill equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organize to form functional NMJ connections within two weeks. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium transient imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-culture. This demonstrates that the 3D co-culture system supports a developmental shift from the embryonic to adult form of the receptor that does not occur in 2D co-culture. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. This work delivers a simple, reproducible, and adaptable method to model and evaluate adult human NMJ de novo development and disease in culture.

Using 3D printed physical models to monitor knowledge integration in biochemistry

2018 ◽  
Vol 19 (4) ◽  
pp. 1199-1215 ◽  
Author(s):  
Melissa A. Babilonia-Rosa ◽  
H. Kenny Kuo ◽  
Maria T. Oliver-Hoyo
Keyword(s):  
Small Molecules ◽  
Knowledge Integration ◽  
Noncovalent Interactions ◽  
Three Dimensional ◽  
Student Understanding ◽  
Physical Models ◽  
Dimensional Structure ◽  
Instructional Resources ◽  
3D Printed ◽  
Different Sources

Noncovalent interactions determine the three-dimensional structure of macromolecules and the binding interactions between molecules. Students struggle to understand noncovalent interactions and how they relate to structure–function relationships. Additionally, students’ difficulties translating from two-dimensional representations to three-dimensional representations add another layer of complexity found in macromolecules. Therefore, we developed instructional resources that use 3D physical models to target student understanding of noncovalent interactions of small molecules and macromolecules. To this effect, we monitored indicators of knowledge integration as evidenced in student-generated drawings. Analysis of the drawings revealed that students were able to incorporate relevant conceptual features into their drawings from different sources as well as present their understanding from different perspectives.

Artificial Myocardium: Design Principles and Substratum

2001 ◽  
Vol 7 (S2) ◽  
pp. 138-139
Author(s):  
Michael Yost ◽  
Robert Price ◽  
David Simpson ◽  
Louis Terracio
Keyword(s):  
Gap Junctions ◽  
Three Dimensional ◽  
Surgical Techniques ◽  
Disease Process ◽  
The United States ◽  
Dimensional Structure ◽  
Muscular Tissue ◽  
Cardiac Muscle Cells ◽  
Functional Relationships ◽  
Electrical Pacing

Death and disability due to cardiovascular disease and congenital anomalies remains a significant health problem in the United States. Despite improvements in detection, patient management, surgery and preventative medicine, the quality of life for people who suffer from cardiovascular dysfunction has a major impact on our society. The intact heart is an elaborate three-dimensional structure that insures the orderly propagation of electrical signals coordinating the contraction and relaxation of the ventricular wall. Localized loss of muscular tissue as a result of congenital defect or disease process alters this structural arrangement and impairs overall cardiac function. Conventional surgical techniques cannot begin to adequately restore the subtle structural and functional relationships in the heart. The ability to construct a tissue-engineered prosthesis composed of cardiac muscle cells in a collagen-based scaffold may potentially offer a superior alternative to currently available surgical techniques.A tissue engineered myocardium must have the following components: First, it must develop and maintain the correct cellular phenotype as well as a functioning contractile apparatus of parallel myofibrils, Second it must be able to form gap junctions within itself and with the native tissue and these gap junctions must be competent at conducting electrical pacing as well as other biochemical signals, and Third, it must be capable of participating in and contributing to the rhythmic contraction of normal myocardium as well as accommodate the changes in contraction frequency ubiquitous in the cardiac environment

scholarly journals Muscular dystrophy in a dish: engineered human skeletal muscle mimetics for disease modeling and drug discovery

2016 ◽  
Vol 21 (9) ◽  
pp. 1387-1398 ◽  
Author(s):  
Alec S.T. Smith ◽  
Jennifer Davis ◽  
Gabsang Lee ◽  
David L. Mack ◽  
Deok-Ho Kim
Keyword(s):  
Skeletal Muscle ◽  
Drug Discovery ◽  
Muscular Dystrophy ◽  
Human Skeletal Muscle ◽  
Disease Modeling

scholarly journals A 96-well culture platform enables longitudinal analyses of engineered human skeletal muscle microtissue strength

2019 ◽  
Author(s):  
Mohammad E. Afshar ◽  
Haben Y. Abraha ◽  
Mohsen A. Bakooshli ◽  
Sadegh Davoudi ◽  
Nimalan Thavandiran ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Disease Modeling ◽  
Toxicity Testing ◽  
Contractile Force ◽  
Single Step ◽  
Device Fabrication ◽  
Research Approach ◽  
Skeletal Muscle Function

ABSTRACTThree-dimensional (3D) in vitro models of human skeletal muscle mimic aspects of native tissue structure and function, thereby providing a promising system for disease modeling, drug discovery or pre-clinical validation, and toxicity testing. Widespread adoption of this research approach is hindered by the lack of an easy-to-use platform that is simple to fabricate and yields arrays of human skeletal muscle micro-tissues (hMMTs) in culture with reproducible physiological responses that can be assayed non-invasively. Here, we describe a design and methods to generate a reusable mold to fabricate a 96-well platform, referred to as MyoTACTIC, that enables bulk production of 3D hMMTs. All 96-wells and all well features are cast in a single step from the reusable mold. Non-invasive calcium transient and contractile force measurements are performed on hMMTs directly in MyoTACTIC, and unbiased force analysis occurs by a custom automated algorithm, allowing for longitudinal studies of function. Characterizations of MyoTACTIC and resulting hMMTs confirms the reproducibility of device fabrication and biological responses. We show that hMMT contractile force mirrors expected responses to compounds shown by others to decrease (dexamethasone, cerivistatin) or increase (IGF-1) skeletal muscle strength. Since MyoTACTIC supports hMMT long-term culture, we evaluated direct influences of pancreatic cancer chemotherapeutics agents on contraction competent human skeletal muscle fibers. A single application of a clinically relevant dose of Irinotecan decreased hMMT contractile force generation, while clear effects on fiber atrophy were observed histologically only at a higher dose. This suggests an off-target effect that may contribute to cancer associated muscle wasting, and highlights the value of the MyoTACTIC platform to non-invasively predict modulators of human skeletal muscle function.

scholarly journals Muscling in on the third dimension

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mohsen Afshar Bakooshli ◽  
Penney M Gilbert
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Human Skeletal Muscle ◽  
Three Dimensional ◽  
Dimensional Model ◽  
Three Dimensional Model ◽  
Muscle Disorders ◽  
The Third ◽  
Third Dimension ◽  
Skeletal Muscle Disorders

The development of a functional three-dimensional model of human skeletal muscle tissue could accelerate progress towards new and personalized treatments for skeletal muscle disorders.

scholarly journals Information-Driven Design as a Potential Approach for 3D Printing of Skeletal Muscle Biomimetic Scaffolds

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1986
Author(s):  
Silvia Baiguera ◽  
Costantino Del Gaudio ◽  
Felicia Carotenuto ◽  
Paolo Di Nardo ◽  
Laura Teodori
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Healing Process ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Muscle Injuries ◽  
Clinical Issue ◽  
Potential Approach ◽  
Biomimetic Scaffolds ◽  
Experimental Protocols

Severe muscle injuries are a real clinical issue that still needs to be successfully addressed. Tissue engineering can represent a potential approach for this aim, but effective healing solutions have not been developed yet. In this regard, novel experimental protocols tailored to a biomimetic approach can thus be defined by properly systematizing the findings acquired so far in the biomaterials and scaffold manufacturing fields. In order to plan a more comprehensive strategy, the extracellular matrix (ECM), with its properties stimulating neomyogenesis and vascularization, should be considered as a valuable biomaterial to be used to fabricate the tissue-specific three-dimensional structure of interest. The skeletal muscle decellularized ECM can be processed and printed, e.g., by means of stereolithography, to prepare bioactive and biomimetic 3D scaffolds, including both biochemical and topographical features specifically oriented to skeletal muscle regenerative applications. This paper aims to focus on the skeletal muscle tissue engineering sector, suggesting a possible approach to develop instructive scaffolds for a guided healing process.

scholarly journals Three-dimensional structure of the Z band in a normal mammalian skeletal muscle.

1996 ◽  
Vol 133 (3) ◽  
pp. 571-583 ◽  
Author(s):  
J P Schroeter ◽  
J P Bretaudiere ◽  
R L Sass ◽  
M A Goldstein
Keyword(s):  
Skeletal Muscle ◽  
Cross Sections ◽  
Three Dimensional ◽  
Square Lattice ◽  
Actin Binding ◽  
Dimensional Structure ◽  
Mammalian Skeletal Muscle ◽  
Axial Filament ◽  
Three Dimensional Structure ◽  
Dimensional Reconstruction

The three-dimensional structure of the vertebrate skeletal muscle Z band reflects its function as the muscle component essential for tension transmission between successive sarcomeres. We have investigated this structure as well as that of the nearby I band in a normal, unstimulated mammalian skeletal muscle by tomographic three-dimensional reconstruction from electron micrograph tilt series of sectioned tissue. The three-dimensional Z band structure consists of interdigitating axial filaments from opposite sarcomeres connected every 18 +/- 12 nm (mean +/- SD) to one to four cross-connecting Z-filaments are observed to meet the axial filaments in a fourfold symmetric arrangement. The substantial variation in the spacing between cross-connecting Z-filament to axial filament connection points suggests that the structure of the Z band is not determined solely by the arrangement of alpha-actinin to actin-binding sites along the axial filament. The cross-connecting filaments bind to or form a "relaxed interconnecting body" halfway between the axial filaments. This filamentous body is parallel to the Z band axial filaments and is observed to play an essential role in generating the small square lattice pattern seen in electron micrographs of unstimulated muscle cross sections. This structure is absent in cross section of the Z band from muscles fixed in rigor or in tetanus, suggesting that the Z band lattice must undergo dynamic rearrangement concomitant with crossbridge binding in the A band.

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