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Research Interests:
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.
Recent
Publications:
Larkin LM, Calve S, Kostrominova TY, Arruda EM. Structure and functional evaluation of tendon-skeletal muscle constructs engineered in vitro. Tissue Eng. 2006 Nov;12(11):3149-58.
Hanes MC, Weinzweig J, Kuzon WM, Panter KE, Buchman SR, Faulkner JA, Yu D, Cederna PS, Larkin LM. Contractile properties of single permeabilized muscle fibers from congenital cleft palates and normal palates of Spanish goats. Plast Reconstr Surg. 2007 May;119(6):1685-94.
Larkin LM, Van der Meulen JH, Dennis RG, Kennedy JB. Functional evaluation of nerve-skeletal muscle constructs engineered in vitro.In Vitro Cell Dev Biol Anim. 2006 Mar-Apr;42(3-4):75-82.
Baker EL, Dennis RG, Larkin LM. Glucose transporter content and glucose uptake in skeletal muscle constructs engineered in vitro. In Vitro Cell Dev Biol Anim. 2003 Nov-Dec;39(10):434-9.
Larkin LM, Kuzon WM Jr, Halter JB. Synergist muscle ablation and recovery from nerve-repair grafting: contractile and metabolic function. J Appl Physiol. 2000 Oct;89(4):1469-76.
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