Within 5 weeks, denervated extensor digitorum longus (EDL) muscles of rats lose 66% of mass, 91% of force, and 76% of fiber cross-sectional area (CSA). We previously determined the parameters of electrical stimulation for denervated rat EDL muscles to generate tetanic contractions sufficient to maintain mass and force close to control values. Using these parameters, we tested the hypothesis that a range exists for number of contractions per day, below and above which values for mass, maximum force, and fiber CSA are lower than values for innervated control muscles. For 5 weeks, denervated EDL muscles were stimulated to generate between 25 and 5000 contractions daily with contractions separated by constant intervals of rest, repeated 24 h per day. Force was not maintained with fewer than 200 or more than 800 contractions daily, whereas mass and fiber CSA were not maintained with fewer than 50 contractions daily. Protocols of stimulation that maintain muscle mass and force during prolonged periods of denervation may minimize problems clinically associated with denervation atrophy.

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A tissue-engineered small-diameter arterial graft would be of benefit to patients requiring vascular reconstructive procedures. Our objective was to produce a tissue-engineered vascular graft with a high patency rate that could withstand arterial pressures. Rat arteries were acellularized with a series of detergent solutions, recellularized by incubation with a primary culture of endothelial cells, and implanted as interposition grafts in the common femoral artery. Acellular grafts that had not been recellularized were implanted in a separate group of control animals. No systemic anticoagulants were administered. Grafts were explanted at 4 weeks for definitive patency evaluation and histologic examination; 89% of the recellularized grafts and 29% of the control grafts remained patent. Elastin staining demonstrated the preservation of elastic fibers within the media of the acellular grafts before implantation. Immunohistochemical staining of explanted grafts demonstrated a complete layer of endothelial cells on the lumenal surface in grafts that remained patent. Smooth muscle cells were observed to have repopulated the vessel walls. The mechanical properties of the matrix were comparable to native vessels. Such a strategy may present an alternative to autologous harvest of small vessels for use in vascular bypass procedures.

. Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles.

Three-dimensional, vascularized skeletal muscle can be engineered in vivo. The resulting tissues have histologic and functional properties consistent with native skeletal muscle.