Abstract
Developing new approaches for vascularizing synthetic tissue systems will have a tremendous impact in diverse areas. One area where this is particularly important is developing new skeletal muscle tissue systems, which could be utilized in physiological model studies and tissue regeneration. To develop vascularized approaches a microfluidic on-chip design for creating channels in polymer systems can be pursued. Current microfluidic tissue engineering methods include soft lithography, rapid prototyping, and cell printing; however, these have limitations such as having their scaffolding being inorganic, less desirable planar vasculature geometry, low fabrication efficiency, and limited resolution. Here we successfully developed a circular microfluidic channel embedded in a 3D extracellular matrix scaffolding with 3D myogenesis. We used a thermo-responsive polymer approach with micromilling-molding and designed a mixture of polyester wax and paraffin wax to fabricate the sacrificial template for microfluidic channel generation in the scaffolding. These findings will impact a number of fields including biomaterials, biomimetic structures, and personalized medicine in the future.
Highlights
Skeletal muscle tissue is critical in musculoskeletal systems especially with respect to force generation [1] as they contain myofibers with a high density of myotubes that are aligned in three-dimensional (3D) extracellular matrix (ECM) [2]
One potential approach is to use skeletal muscle cell lines such as C2C12 cells, which have been used in a variety of in vitro models including microfluidics [3,4] and are well studied in areas such as myogenesis and contraction [5,6,7]
HUVEC cells were suspended in culture media (DMEM+10%FBS) at a density of 1 million cells/mL and introduced into the channel inside the crosslinked ECM (C2C12 cells were pre-cultured in the ECM) and incubated for 4 h
Summary
Skeletal muscle tissue is critical in musculoskeletal systems especially with respect to force generation [1] as they contain myofibers with a high density of myotubes that are aligned in three-dimensional (3D) extracellular matrix (ECM) [2]. While this tissue is important for many functions, in vivo muscle tissues have limited regeneration abilities such as in injury and aging [1]. Biomimetic engineering muscle systems may be an effective approach to create in vivo muscle tissues that could be used in a diversity of areas including during surgery, and reconstruction. Live cells were stained in green (Calcein AM) and dead cell in red (Ethidium homodimer)
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