VEGF improves skeletal muscle regeneration after acute trauma and reconstruction of the limb in a rabbit model.
BACKGROUND
Complicated tibial fractures with severe soft tissue trauma are challenging to treat. Frequently associated acute compartment syndrome can result in scarring of muscles with impaired function. Several studies have shown a relationship between angiogenesis and more effective muscle regeneration. Vascular endothelial growth factor (VEGF) is associated with angiogenesis but it is not clear whether it would restore muscle force, reduce scarring, and aid in muscle regeneration after acute musculoskeletal trauma.


OBJECTIVE
Therefore, we asked whether local application of VEGF (1) restores muscle force, (2) reduces scar tissue formation, and (3) regenerates muscle tissue.


METHODS
We generated acute soft tissue trauma with increased compartment pressure in 22 rabbits and shortened the limbs to simulate fracture débridement. In the test group (n = 11), a VEGF-coated collagen matrix was applied locally around the osteotomy site. After 10 days of limb shortening, gradual distraction of 0.5 mm per 12 hours was performed to restore the original length. Muscle force was measured before trauma and on every fifth day after trauma. Forty days after shortening we euthanized the animals and histologically determined the percentage of connective and muscle tissue.


RESULTS
Recovery of preinjury muscle strength was greater in the VEGF group (2.4 N; 73%) when compared with the control (1.8 N; 53%) with less connective and more muscle tissue in the VEGF group. The recovery of force was related to the percentage of connective tissue versus muscle fibers.


CONCLUSIONS
Local application of VEGF may improve restoration of muscle force by reducing connective tissue and increasing the relative amount of muscle fibers.


CONCLUSIONS
VEGF may be useful to improve skeletal muscle repair by modulating muscle tissue regeneration and fibrosis reduction after acute trauma.
Department of Trauma, Hand, Plastic and Reconstructive Surgery, University of Wuerzburg, Oberduerrbacher Str 6, 97080 Wuerzburg, Germany. frey_s@chirurgie.uni-wuerzburg.de
Soenke Percy
SP
Frey
Hendrik
H
Jansen
Michael J
MJ
Raschke
Rainer H
RH
Meffert
Sabine
S
Ochman
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003161:Compartment Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003646:Debridement; D004195:Disease Models, Animal; D017102:Fracture Healing; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D019857:Osteogenesis, Distraction; D010027:Osteotomy; D011817:Rabbits; D020127:Recovery of Function; D012038:Regeneration / Q000187:drug effects*; D013977:Tibia / Q000473:pathology / Q000601:surgery; D013978:Tibial Fractures / Q000150:complications* / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology*
D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A