Areas of Interest
End-stage organ failure or tissue loss is one of the most devastating and costly problems in medicine. The creation of engineered musculoskeletal tissue with functional myotendinous (MTJ) and neuromuscular (NMJ) junctions will not only restore the function of complex tissues such as muscle, tendon, and nerve following traumatic injury, but can also be used as a model for studying developmental muscle biology and muscle pharmacology. We have demonstrated that the co-culture of fetal nerve tissue with fetal or engineered tendon and engineered muscle tissue produces constructs with viable muscle-tendon interfaces that remain intact during force production, and viable neuromuscular junctions that advance the phenotype of the muscle tissue within the construct. The tissues formed express neonatal structures and do not substantially advance functionally or phenotypically in the absence of electrical or mechanical loading. The purpose of our research is to design, fabricate, and evaluate the structural and contractile characteristics of three-dimensional (3-D) engineered tissues containing myotendinous junctions (MTJ) and neuromuscular junctions (NMJ), two of the principal tissue interfaces required for a functional musculoskeletal construct. We propose to study the long-term viability of these constructs; to increase the expression of neurotrophic proteins like glial derived neurotrophic factor and introduce synthetic, engineered, and tissue based conduits to enhance innervation of the muscle constructs; to use bioreactors to place the nerve-tendon-muscle constructs into physical environments which simulate the stress, strain, and contractile activity resembling the mechanical milieu found in hind limb muscles in vivo; and to implant the constructs in vivo to surround the construct with the actual mechanical and biochemical environment of a hindlimb.
- PhD, University of California, Davis