Abstract Title
Development of a Bioreactor to Mechanically Stimulate Cell Self-Assembled Neotendons
Abstract
Tendon injuries are common but current repair methods are inadequate. Even with surgical repair, scar tissue and incomplete tendon healing result in prolonged weakness which presents a risk for re-rupture. Thus, new regenerative treatment methods are required. To develop new treatments, mesenchymal stem cells (MSCs) have been explored in tissue engineering strategies to form tendon replacements. Our lab has developed a tissue engineering method to guide MSCs to form neotendons through directed cell self-assembly, which appear to mimic the early highly cellular stages of embryonic tendon formation. However, neotendon maturation in culture may be limited without the dynamic mechanical stimulation associated with in vivo muscle contraction. Applying mechanical stimulation is a unique challenge due to the neotendons’ delicate nature and small size. To address this issue, a new bioreactor system was developed using Solidworks modeling software. The bioreactor was designed to be watertight and incorporate a novel loading mechanism that secures and applies tensile loads to the neotendon, while remaining compatible with an existing motor and controller. Before resin 3D printing the bioreactor, resins were tested for cytotoxicity, and minimal changes in cell viability were observed. Using this new bioreactor design, neotendons were dynamically stretched (1% strain at 0.1 Hz for 4 hrs) and the cell morphology was qualitatively evaluated, compared to static controls. Outcomes of this study will advance tendon tissue engineering strategies by improving our understanding of how mechanical loading impacts tendon formation.
Development of a Bioreactor to Mechanically Stimulate Cell Self-Assembled Neotendons
Tendon injuries are common but current repair methods are inadequate. Even with surgical repair, scar tissue and incomplete tendon healing result in prolonged weakness which presents a risk for re-rupture. Thus, new regenerative treatment methods are required. To develop new treatments, mesenchymal stem cells (MSCs) have been explored in tissue engineering strategies to form tendon replacements. Our lab has developed a tissue engineering method to guide MSCs to form neotendons through directed cell self-assembly, which appear to mimic the early highly cellular stages of embryonic tendon formation. However, neotendon maturation in culture may be limited without the dynamic mechanical stimulation associated with in vivo muscle contraction. Applying mechanical stimulation is a unique challenge due to the neotendons’ delicate nature and small size. To address this issue, a new bioreactor system was developed using Solidworks modeling software. The bioreactor was designed to be watertight and incorporate a novel loading mechanism that secures and applies tensile loads to the neotendon, while remaining compatible with an existing motor and controller. Before resin 3D printing the bioreactor, resins were tested for cytotoxicity, and minimal changes in cell viability were observed. Using this new bioreactor design, neotendons were dynamically stretched (1% strain at 0.1 Hz for 4 hrs) and the cell morphology was qualitatively evaluated, compared to static controls. Outcomes of this study will advance tendon tissue engineering strategies by improving our understanding of how mechanical loading impacts tendon formation.