title: Controlled release of IGF-I from a biodegradable matrix improves functional recovery of skeletal muscle from ischemia/reperfusion.
abstract: Ischemia/reperfusion (I/R) injury is a considerable insult to skeletal muscle, often resulting in prolonged functional deficits. The purpose of the current study was to evaluate the controlled release of the pro-regenerative growth factor, insulin-like growth factor-I (IGF-I), from a biodegradable polyethylene glycol (PEG)ylated fibrin gel matrix and the subsequent recovery of skeletal muscle from I/R. To accomplish this, the hind limbs of male Sprague-Dawley rats were subjected to 2-h tourniquet-induced I/R then treated with saline, bolus IGF-I (bIGF), PEGylated fibrin gel (PEG-Fib), or IGF-I conjugated PEGylated fibrin gel (PEG-Fib-IGF). Functional and histological evaluations were performed following 14 days of reperfusion, and muscles from 4-day reperfusion animals were analyzed by Western blotting and histological assessments. There was no difference in functional recovery between saline, bIGF, or PEG-Fib groups. However, PEG-Fib-IGF treatment resulted in significant improvement of muscle function and structure, as observed histologically. Activation of the PI3K/Akt pathway was significantly elevated in PEG-Fib-IGF muscles, compared to PEG-Fib treatment, at 4 days of reperfusion, suggesting involvement of the pathway PI3K/Akt as a mediator of the improved function. Surprisingly, myoblast activity was not evident as a result of PEG-Fib-IGF treatment. Taken together, these data give evidence for a protective role for the delivered IGF. These results indicate that PEG-Fib-IGF is a viable therapeutic technique in the treatment of skeletal muscle I/R injury.
authors.affiliation: Department of Kinesiology, The University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Hammers
authors.forename: Apurva
authors.initials: A
authors.lastname: Sarathy
authors.forename: Chantal B
authors.initials: CB
authors.lastname: Pham
authors.forename: Charles T
authors.initials: CT
authors.lastname: Drinnan
authors.forename: Roger P
authors.initials: RP
authors.lastname: Farrar
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Suggs
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D004343:Drug Implants; D005337:Fibrin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005782:Gels; D006614:Hindlimb / Q000098:blood supply; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction; D014111:Tourniquets
chemical_list: D004337:Drug Carriers; D004343:Drug Implants; D005782:Gels; D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I; D005337:Fibrin; D019869:Phosphatidylinositol 3-Kinases; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt
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