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Front Chem. 2014 Jul 18;2:52. doi: 10.3389/fchem.2014.00052. eCollection 2014.

Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid).

Frontiers in chemistry

Sachiro Kakinoki, Midori Nakayama, Toshiyuki Moritan, Tetsuji Yamaoka

Affiliations

  1. Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute Suita, Japan.
  2. Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute Suita, Japan ; Department of Clinical Engineering, Faculty of Medical Engineering, Suzuka University of Medical Science Suzuka, Japan.
  3. Department of Clinical Engineering, Faculty of Medical Engineering, Suzuka University of Medical Science Suzuka, Japan.

PMID: 25101261 PMCID: PMC4103079 DOI: 10.3389/fchem.2014.00052

Abstract

We developed a microfibrous poly(L-lactic acid) (PLLA) nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG)30) that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical strength to the conduit. A 10% poly(ethylene glycol) was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG)30 compositing of an elastin-like repetitive sequence (VPGIG)30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73) was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG)30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG)30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG)30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG)30 inner layer.

Keywords: elastin-laminin mimetic protein; electrospun microfiber; nerve conduit; poly(L-lactic acid); tissue adhesion prevention

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