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Jenna L. Dziki. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 2 Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.
Ross M. Giglio. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Brian M. Sicari. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 3 Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
Derek S. Wang. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Riddhi M. Gandhi. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 2 Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.
Ricardo Londono. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Christopher L. Dearth. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 3 Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. 4 DoD-VA Extremity Trauma and Amputation Center of Excellence, Walter Reed National Military Medical Center/Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Stephen F. Badylak. 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 2 Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania. 3 Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
*
These authors contributed equally to this work.
Address correspondence to: Stephen F. Badylak, PhD, DVM, MD, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, E-mail: [email protected]
Introduction
Severe skeletal muscle injury, such as volumetric muscle loss (VML), as a result of trauma, tumor ablation, or prolonged denervation, is a challenging problem in civilian and military medicine with significant clinical and economic consequences.1-3 Treatment strategies include muscle grafts, orthotic devices, and/or physical rehabilitation and typically leave patients with a bleak prognosis of persistent strength and functional deficits.4-6 To address this unmet clinical need, a wide variety of strategies in the field of tissue engineering/regenerative medicine have been investigated as alternative therapeutic approaches to VML.
The use of acellular biologic scaffolds composed of mammalian extracellular matrix (ECM) as an inductive myogenic template has been investigated for more than two decades in multiple animal models, a variety of tissues, and types of injury, and with diverse bioscaffold source tissues. Outcomes have ranged from successful to unsatisfactory.7-16 The findings from these preclinical studies served as the basis for the clinical use of ECM bioscaffolds...