Skeletal muscle derived stem cells microintegrated into a biodegradable elastomer for reconstruction of the abdominal wall.
A variety of techniques have been applied to generate tissue engineered constructs, where cells are combined with degradable scaffolds followed by a period of in vitro culture or direct implantation. In the current study, a cellularized scaffold was generated by concurrent deposition of electrospun biodegradable elastomer (poly(ester urethane)urea, PEUU) and electrosprayed culture medium + skeletal muscle-derived stem cells (MDSCs) or electrosprayed culture medium alone as a control. MDSCs were obtained from green fluorescent protein (GFP) transgenic rats. The created scaffolds were implanted into allogenic strain-matched rats to replace a full thickness abdominal wall defect. Both control and MDSC-integrated scaffolds showed extensive cellular infiltration at 4 and 8 wk. The number of blood vessels was higher, the area of residual scaffold was lower, number of multinucleated giant cells was lower and area of connective tissue was lower in MDSC-integrated scaffolds (p < 0.05). GFP + cells co-stained positive for VEGF. Bi-axial mechanical properties of the MDSC-microintegrated constructs better approximated the anisotropic behavior of the native abdominal wall. GFP + cells were observed throughout the scaffold at ∼5% of the cell population at 4 and 8 wk. RNA expression at 4 wk showed higher expression of early myogenic marker Pax7, and b-FGF in the MDSC group. Also, higher expression of myogenin and VEGF were seen in the MDSC group at both 4 and 8 wk time points. The paracrine effect of donor cells on host cells likely contributed to the differences found in vivo between the groups. This approach for the rapid creation of highly-cellularized constructs with soft tissue like mechanics offers an attractive methodology to impart cell-derived bioactivity into scaffolds providing mechanical support during the healing process and might find application in a variety of settings.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Surgery, University of Pittsburgh, USA.
Keisuke
K
Takanari
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Surgery, University of Pittsburgh, USA.
Ryotaro
R
Hashizume
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Surgery, University of Pittsburgh, USA.
Yi
Y
Hong
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Bioengineering, University of Pittsburgh, USA.
Nicholas J
NJ
Amoroso
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Surgery, University of Pittsburgh, USA.
Tomo
T
Yoshizumi
Stem Cell Research Center, University of Pittsburgh, USA; Institute for Complex Engineered Systems, Carnegie Mellon University, USA.
Burhan
B
Gharaibeh
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, USA.
Osamu
O
Yoshida
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Surgery, University of Pittsburgh, USA.
Kazuhiro
K
Nonaka
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Surgery, University of Pittsburgh, USA.
Hideyoshi
H
Sato
Stem Cell Research Center, University of Pittsburgh, USA; Dept. of Orthopedic Surgery, University of Pittsburgh, USA.
Johnny
J
Huard
McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Dept. of Surgery, University of Pittsburgh, USA; Dept. of Bioengineering, University of Pittsburgh, USA; Dept. of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15219, USA. Electronic address: wagnerwr@upmc.edu.
William R
WR
Wagner
D034861:Abdominal Wall / Q000098:blood supply / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002478:Cells, Cultured; D020724:Elastomers / Q000737:chemistry*; D005260:Female; D018482:Muscle, Skeletal / Q000166:cytology*; D011140:Polyurethanes / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing
D001672:Biocompatible Materials; D020724:Elastomers; D011140:Polyurethanes
Biodegradable; Elastomer; Electrospinning; Muscle derived stem cells; Polyurethane; Scaffold