Muscle tissue engineering is a subset of the general field of
tissue engineering
Tissue engineering is a biomedical engineering discipline that uses a combination of Cell (biology), cells, engineering, Materials science, materials methods, and suitable biochemistry, biochemical and physicochemical factors to restore, maintai ...
, which studies the combined use of cells and scaffolds to design therapeutic tissue implants. The major motivation for muscle tissue engineering is to treat a condition called volumetric muscle loss (VML). VML can be caused by a variety of injuries or diseases, including
general trauma, postoperative damage,
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
ablation,
congenital defect
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at childbirth, birth regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellect ...
s, and degenerative
myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
.
[VanDusen KW, Syverud BC, Williams ML, Lee JD, Larkin LM. 2014. Engineered skeletal muscle units for repair of volumetric muscle loss in the tibialis anterior muscle of a rat. Tissue Engineering.Part A 20(21-22):2920.]
Although
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
contains a stem cell population called
satellite cells that are capable of regenerating small muscle injuries, muscle damage in VML is so extensive that it overwhelms muscle's natural regenerative capabilities. Currently VML is treated through an autologous muscle flap or graft but there are various problems associated with this procedure. Donor site morbidity, lack of donor tissue, and inadequate vascularization all limit the ability of doctors to adequately treat VML.
The field of muscle tissue engineering attempts to address this problem through the design of a functional muscle construct that can be used to treat the damaged muscle instead of harvesting an autologous muscle flap from elsewhere on the patient's body.
Muscle is a naturally aligned organ, with individual muscle fibers packed together into larger units called
muscle fascicles. The uniaxial alignment of
muscle fibers allows them to simultaneously contract in the same direction and properly propagate force on the
bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s via the
tendon
A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...
s. A major focus of muscle tissue engineering is to create constructs with the functionality of native muscle and ability to contract. To this end, alignment of the tissue engineered construct is extremely important. It has been shown that cells grown on substrates with alignment cues form more robust muscle fibers. Several other design criteria considered in muscle tissue engineering include the scaffold porosity, stiffness, biocompatibility, and degradation timeline. Substrate stiffness should ideally be in the
myogenic range, which has been shown to be 10-15 kPa.
[Choi, Y., Vincent, L.G., Lee, A.R., Dobke, M.K., Engler, A.J., Mechanical derivation of functional myotubes from adipose-derived stem cells. Biomaterials, 2012. 33: p. 2484-2491.]
Functional analysis of a tissue engineered muscle construct is important to illustrate its potential to help regenerate muscle. A variety of assays are generally used to evaluate a tissue engineered muscle construct including
immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
,
RT-PCR
Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase cha ...
, electrical stimulation and resulting peak-to-peak
voltage
Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...
,
scanning electron microscope imaging, and in vivo response.
References
Tissue engineering