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Enhancement of Neovascularization in Regenerating Skeletal Muscle by the Sustained Release of Erucamide from a Polymer Matrix

Department of Pathology, University of Western Australia, Nedlands, Western Australia 6009, Australia

Marilyn J. Davies

Department of Pathology, University of Western Australia, Nedlands, Western Australia 6009, Australia

Miranda D. Grounds

Department of Pathology, University of Western Australia, Nedlands, Western Australia 6009, Australia

John K. McGeachie

Department of Anatomy and Human Biology, University of Western Australia, Nedlands, Western Australia 6009, Australia

Geoffrey J. Crawford

Lions Eye Institute, 2 Verdun Street, Block A, Nedlands, Western Australia 6009, Australia

Ye Hong

Lions Eye Institute, 2 Verdun Street, Block A, Nedlands, Western Australia 6009, Australia

Traian V. Chirila

Lions Eye Institute, 2 Verdun Street, Block A, Nedlands, Western Australia 6009, Australia

The angiogenic agent erucamide (cis-13-docosenamide), incorporated into a polymeric biomaterial (Elvax® 40P, a copolymer of ethylene and vinyl acetate), was used to determine whether angiogenesis can be increased in the regenerating skeletal muscle, and whether the enhanced revascularization improves the new muscle formation. The angiogenic nature of this lipid was confirmed in a rat cornea-micropocket assay, prior to insertion of small strips of the polymer containing either 3 µg, 30 µg, 300 µg erucamide or only polymer as a control into the mid-region of crush-injured tibialis anterior (TA) muscles of forty-five adult male BALB/c mice. All TA muscles were sampled ten days after injury and analyzed morphometrically. Statistical analyses of the mean blood vessel area density in lesions from twelve perfused TA muscles (three from each of the erucamide-treated or control group), revealed a dose-dependent angiogenic effect of erucamide: a dosage of 3 µg increased mean blood vessel area density to 5.1% compared to 2.0% in controls, due to numerous large caliber, thin-walled vessels, whereas the mean vessel area density in both the 30-µg (3.5%) and 300-µg (1.5%) doses were similar to controls. However, at all three doses tested, erucamide did not significantly alter the degree of new muscle formation, connective tissue deposition, or removal of necrotic debris.

Key Words: neovascularization • skeletal muscle • erucamide • Elvax copolymer • sustained release • regeneration

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