Hydroxyapatite-coated tendon chitosan tubes with adsorbed laminin peptides facilitate nerve regeneration in vivo.
On the inner surface of tendon chitosan tubes having a triangular shape and a hydroxyapatite coating (t-chitosan/HAp tube), laminin-1 and laminin peptides (YIGSR, IKVAV) have been adsorbed in order to develop nerve growth conduits. The mechanical property, biocompatibility and efficacy of these tubes for nerve regeneration were examined. Step-1: bridge grafting (15 mm) into the sciatic nerve of Sprague-Dawley (SD) rats was carried out using either t-chitosan or t-chitosan/HAp tubes having either a circular or triangular cross section (N=12 in each group). Specimens were taken after 2-, 4-, 6- and 8-week post-implantation (N=3 in each group) for histology determinations. Step-2: t-chitosan/HAp tubes having a triangular cross section with adsorbed laminin-1, CDPGYIGSR or CSRARKQAASIKVAVSAD, as well as control tubes without pre-adsorption were used for implantation (N=18 in each group). Isografting was also carried out (N=6). Histological evaluation was carried out similarly as in Step-1. Furthermore, evoked muscle and sensory nerve action potentials were recorded, and the percentage of myelinated axon area measured at 10 mm distance of the distal anastomosed site in the experimental, control and isograft groups after 12 weeks (N=6 in each group). The results of histological findings, as well as mechanical properties, suggest that a triangular tube shape with a HAp coating benefits nerve regeneration. The effect of laminin peptides (YIGSR, followed by IKVAV) to enhance the growth of regenerating axons has been found comparable with intact laminin-1. Although histological regeneration in both the YIGSR- and laminin-1-treated t-chitosan/HAp tubes matches the isografts, the functional recovery is however delayed.
Itoh
Soichiro
S
Division of Molecular Tissue Engineering, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo, Tokyo 113-8519, Japan. itoso.gene@cmn.tmd.ac.jp
Yamaguchi
Isamu
I
Suzuki
Masumi
M
Ichinose
Shizuko
S
Takakuda
Kazuo
K
Kobayashi
Hisatoshi
H
Shinomiya
Kenichi
K
Tanaka
Junzo
J
D000818:Animals; D003386:Brachyura; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048271:Chitosan; D020099:Coated Materials, Biocompatible; D004357:Drug Synergism; D017886:Durapatite / Q000737:chemistry*; D005071:Evoked Potentials / Q000187:drug effects; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology / Q000637:transplantation / Q000648:ultrastructure; D020426:Sciatic Neuropathy / Q000473:pathology / Q000628:therapy; D013314:Stress, Mechanical; D013710:Tendons / Q000187:drug effects* / Q000637:transplantation / Q000648:ultrastructure; D013997:Time Factors; D019737:Transplants
D020099:Coated Materials, Biocompatible; D007797:Laminin; D010455:Peptides; C121346:laminin 1; D002686:Chitin; D048271:Chitosan; D017886:Durapatite