title: Synergistic improvements in cell and axonal migration across sciatic nerve lesion gaps using bioresorbable filaments and heregulin-beta1.
abstract: The success of entubulation for peripheral nerve regeneration is still limited, especially with long lesion gaps. In this study, we examined if regeneration could be enhanced by constructing implants to both align axonal growth and promote Schwann cell proliferation and migration. Silicone implants were used to bridge a 1.4-cm gap in the rat sciatic nerve. Adult female Sprague-Dawley rats were divided into four groups of tubes containing either 1) Matrigel; 2) Matrigel and heregulin; 3) Matrigel and poly(L-lactic acid) (PLLA) microfilaments; or 4) Matrigel, PLLA microfilaments, and heregulin. Ten weeks postimplantation, the number of axons and Schwann cells were measured at the distal end of implants. Implants with microfilaments displayed better tissue cable formation, increased Schwann cell migration, and regeneration of anti-calcitonin gene-related peptide-positive axons, but not RMDO95-positive axons compared with nonfilament-containing groups. Heregulin treatment caused an increase in Schwann cell number, but it demonstrated no significant improvement in either tissue cable formation or axon number. Extensive regeneration was observed through implants containing Matrigel, microfilaments, and heregulin, which induced significant improvements in the number and longitudinal organization of both Schwann cells and axons. These results indicate that physical guidance of microfilaments and the Schwann cell growth factor, heregulin, act synergistically to improve nerve regeneration across long lesion gaps.
authors.affiliation: Department of Physiology MS 508, University of Kentucky, Albert B. Chandler Medical Center, Lexington, Kentucky 40536-0298, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.forename: Xuejun
authors.initials: X
authors.lastname: Peng
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Nelson
authors.forename: Robert
authors.initials: R
authors.lastname: Eberhart
authors.forename: George M
authors.initials: GM
authors.lastname: Smith
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001672:Biocompatible Materials / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D019344:Lactic Acid; D007797:Laminin; D009416:Nerve Regeneration / Q000502:physiology*; D020890:Neuregulin-1 / Q000378:metabolism*; D011091:Polyesters; D011108:Polymers; D019736:Prostheses and Implants; D011509:Proteoglycans; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology*; D012825:Silicon
chemical_list: D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D020890:Neuregulin-1; D011091:Polyesters; D011108:Polymers; D011509:Proteoglycans; C059485:matrigel; C087230:heregulin beta1; D019344:Lactic Acid; C033616:poly(lactide); D003094:Collagen; D012825:Silicon