60. ENGINEERED 3D SKELETAL MUSCLE-ON-A-CHIP AS AN IN VITRO TOOL

Department: Bioengineering
Faculty Advisor(s): Shyni Varghese

Primary Student
Name: Gaurav Agrawal
Email: gagrawal@ucsd.edu
Phone: 858-822-7986
Grad Year: 2018

Abstract
Skeletal muscle can comprise up to 50% of a person's body mass. As such, any condition that affects this tissue can severely hinder quality of life, even leading to death in extreme cases. Drug development in this field has traditionally relied either on cells cultured on two-dimensional (2D) surfaces in a plastic dish or on animal models to evaluate toxicity or efficacy during the preclinical phase. However, these models are unreliable and inefficient. The 2D screens fail to capture the complex cell-cell and cell-extracellular matrix (ECM) interactions found in human tissue, and rarely yield any indication of the effect on muscle function. Further, in addition to their high cost of care and maintenance, animals are fundamentally different species than humans and the results from these studies do not translate well to the clinic. Ultimately, these tests fail to predict drug effect in humans as proven by the high attrition rate late in clinical trials. To provide an alternative platform, we have used physicochemical cues to engineer a 3D skeletal muscle bundle within a microfluidic device that recapitulates the architectural and structural complexities of native muscle. Using a 3D photo-patterning technology, we spatially control the placement of cells within a collagen-derived ECM around two anchoring points. A nascent tissue forms during the first 2 days and undergoes growth and remodeling to further mature for the ensuing 12 days, during which cell fusion and alignment occurs, both of which we have quantified. Further, we have developed a method to calculate the tensile forces generated by the engineered muscle strip during tissue maturation. Our initial studies have utilized mouse myoblasts to establish the system, but we are actively moving towards using human induced pluripotent stem cells (hiPSCs) as these allow for modeling of genetic diseases such as Duchenne muscular dystrophy (DMD). This physiologically-relevant system can be used for a variety of purposes such as the functional screening of small molecules or biologics in the pharmaceutical industry. Further, this may be used as a preliminary screen to evaluate hiPSC engraftment potential for cell-based therapies.

Industry Application Area(s)
Life Sciences/Medical Devices & Instruments

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