Engineering an Injectable Muscle-Specific Microenvironment for Improved Cell Delivery Using a Nanofibrous Extracellular Matrix Hydrogel.
Injection of skeletal muscle progenitors has the potential to be a minimally invasive treatment for a number of diseases that negatively affect vasculature and skeletal muscle, including peripheral artery disease. However, success with this approach has been limited because of poor transplant cell survival. This is primarily attributed to cell death due to extensional flow through the needle, the harsh ischemic environment of the host tissue, a deleterious immune cell response, and a lack of biophysical cues supporting exogenous cell viability. We show that engineering a muscle-specific microenvironment, using a nanofibrous decellularized skeletal muscle extracellular matrix hydrogel and skeletal muscle fibroblasts, improves myoblast viability and maturation in vitro. In vivo, this translates to improved cell survival and engraftment and increased perfusion as a result of increased vascularization. Our results indicate that a combinatorial delivery system, which more fully recapitulates the tissue microenvironment, can improve cell delivery to skeletal muscle.
Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego , La Jolla, California 92037, United States.
Nikhil
N
Rao
Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego , La Jolla, California 92037, United States.
Gillie
G
Agmon
Matthew T
MT
Tierney
Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego , La Jolla, California 92037, United States.
Jessica L
JL
Ungerleider
Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego , La Jolla, California 92037, United States.
Rebecca L
RL
Braden
Alessandra
A
Sacco
Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego , La Jolla, California 92037, United States.
Karen L
0000-0002-6179-898X
KL
Christman
D000818:Animals; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D057139:Nanofibers / Q000008:administration & dosage / Q000737:chemistry*; D023822:Tissue Engineering
D020100:Hydrogels
biomaterial; cell delivery; cell microenvironment; injectable; muscle; myoblast; peripheral artery disease