Following injury, the inherent regenerative response of skeletal muscle depends on an activated microenvironment consisting of muscle progenitor cells and a heterogeneous macrophage phenotype. These microenvironmental factors can be negatively impacted through musculoskeletal disease, volumetric muscle loss (VML), and the decreased regenerative capacity of stem cells and immunosenesence associated with advanced age. Biologic scaffolds composed of extracellular matrix (ECM) have been used to promote the constructive remodeling of defects in a variety of soft tissues. These surgically placed scaffolds are composed of growth factors and matricryptic peptides which are able to positively impact the skeletal muscle microenvironment by recruiting progenitor cells and promoting an M1 to M2 macrophage phenotypic transition. Furthermore, ECM scaffolds have been used to effectively augment the skeletal muscle response to VML. The current proposal seeks to examine the ability of ECM scaffolds to mitigate age-related changes to the skeletal muscle microenvironment through increased myogenic progenitor cell recruitment and modulation of macrophage phenotype.

Public Health Relevance

The aging process alters the skeletal muscle microenvironment and negatively impacts its inherent regenerative response to injury. Surgically placed biologic scaffolds composed of extracellular matrix (ECM) have been shown to promote a regenerative skeletal muscle microenvironment. The current proposal examines the ability of ECM scaffolds to mitigate age-related changes to the skeletal muscle response to injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AG042199-02
Application #
8459641
Study Section
Special Emphasis Panel (ZRG1-F10B-S (20))
Program Officer
Williams, John
Project Start
2012-03-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
2
Fiscal Year
2013
Total Cost
$39,164
Indirect Cost
Name
University of Pittsburgh
Department
Surgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Sicari, Brian M; Rubin, J Peter; Dearth, Christopher L et al. (2014) An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Sci Transl Med 6:234ra58
Sicari, Brian M; Dziki, Jenna L; Siu, Bernard F et al. (2014) The promotion of a constructive macrophage phenotype by solubilized extracellular matrix. Biomaterials 35:8605-12