Tissue-engineered axially vascularized contractile skeletal muscle.
BACKGROUND
As tissue-engineered muscle constructs increase in scale, their size is limited by the need for a vascular supply. In this work, the authors demonstrate a method of producing three-dimensional contractile skeletal muscles in vivo by incorporating an axial vascular pedicle.


METHODS
Primary myoblast cultures were generated from adult F344 rat soleus muscle. The cells were suspended in a fibrinogen hydrogel contained within cylindrical silicone chambers, and situated around the femoral vessels in isogeneic adult recipient rats. The constructs were allowed to incubate in vivo for 3 weeks, at which point they were explanted and subjected to isometric force measurements and histologic evaluation.


RESULTS
The resulting three-dimensional engineered skeletal muscle constructs produced longitudinal contractile force when electrically stimulated. Length-tension, force-voltage, and force-frequency relationships were similar to those found in developing skeletal muscle. Desmin staining demonstrated that individual myoblasts had undergone fusion to form multinucleated myotubes. Von Willebrand staining showed that the local environment within the chamber was richly angiogenic, and capillaries had grown into and throughout the constructs from the femoral artery and vein.


CONCLUSIONS
Three-dimensional, vascularized skeletal muscle can be engineered in vivo. The resulting tissues have histologic and functional properties consistent with native skeletal muscle.
Borschel
Gregory H
GH
Section of Plastic Surgery and Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Dow
Douglas E
DE
Dennis
Robert G
RG
Brown
David L
DL
D000818:Animals; D021522:Bioartificial Organs; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D003893:Desmin / Q000032:analysis; D004558:Electric Stimulation; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007537:Isometric Contraction; D008567:Membranes, Artificial; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000737:chemistry / Q000502:physiology; D032446:Myoblasts / Q000737:chemistry / Q000502:physiology*; D018919:Neovascularization, Physiologic; D009940:Organoids / Q000098:blood supply* / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000379:methods*; D014841:von Willebrand Factor / Q000032:analysis
D003893:Desmin; D008567:Membranes, Artificial; D014841:von Willebrand Factor; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate