An Acellular Biologic Scaffold Promotes Skeletal Muscle Formation in Mice and Humans with Volumetric Muscle Loss

BIOMATERIALS

1. Brian M. Sicari¹,²,*,
2. J. Peter Rubin¹,³,⁴,*,
3. Christopher L. Dearth¹,²,
4. Matthew T. Wolf¹,⁴,
5. Fabrisia Ambrosio¹,⁵,
6. Michael Boninger¹,⁴,⁵,
7. Neill J. Turner¹,²,
8. Douglas J. Weber⁴,⁵,
9. Tyler W. Simpson⁵,
10. Aaron Wyse⁶,
11. Elke H. P. Brown⁵,
12. Jenna L. Dziki¹,⁴,
13. Lee E. Fisher⁵,
14. Spencer Brown¹,³ and
15. Stephen F. Badylak¹,²,†

1. ¹McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
2. ²Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
3. ³Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
4. ⁴Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
5. ⁵Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15219, USA.
6. ⁶Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15219, USA.

1. ↵†Corresponding author. E-mail: badylaks{at}upmc.edu

• ↵* These authors contributed equally to this work.

Abstract

Biologic scaffolds composed of naturally occurring extracellular matrix (ECM) can provide a microenvironmental niche that alters the default healing response toward a constructive and functional outcome. The present study showed similarities in the remodeling characteristics of xenogeneic ECM scaffolds when used as a surgical treatment for volumetric muscle loss in both a preclinical rodent model and five male patients. Porcine urinary bladder ECM scaffold implantation was associated with perivascular stem cell mobilization and accumulation within the site of injury, and de novo formation of skeletal muscle cells. The ECM-mediated constructive remodeling was associated with stimulus-responsive skeletal muscle in rodents and functional improvement in three of the five human patients.