title: Use of PLGA 90:10 scaffolds enriched with in vitro-differentiated neural cells for repairing rat sciatic nerve defects.
abstract: Poly(lactic-co-glycolic acid) (PLGA) nerve tube guides, made of a novel proportion (90:10) of the two polymers, poly(L-lactide): poly(glycolide) and covered with a neural cell line differentiated in vitro, were tested in vivo for promoting nerve regeneration across a 10-mm gap of the rat sciatic nerve. Before in vivo testing, the PLGA 90:10 tubes were tested in vitro for water uptake and mass loss and compared with collagen sheets. The water uptake of the PLGA tubes was lower, and the mass loss was more rapid and higher than those of the collagen sheets when immersed in phosphate-buffered saline (PBS) solution. The pH values of immersing PBS did not change after soaking the collagen sheets and showed to be around 7.4. On the other hand, the pH values of PBS after soaking PLGA tubes decreased gradually during 10 days reaching values around 3.5. For the in vivo testing, 22 Sasco Sprague adult rats were divided into four groups--group 1: gap not reconstructed; group 2: gap reconstructed using an autologous nerve graft; group 3: gap reconstructed with PLGA 90:10 tube guides; group 4: gap reconstructed with PLGA 90:10 tube guides covered with neural cells differentiated in vitro. Motor and sensory functional recovery was evaluated throughout a healing period of 20 weeks using sciatic functional index, static sciatic index, extensor postural thrust, withdrawal reflex latency, and ankle kinematics. Stereological analysis was carried out on regenerated nerve fibers. Both motor and sensory functions improved significantly in the three experimental nerve repair groups, although the rate and extent of recovery was significantly higher in the group where the gap was reconstructed using the autologous graft. The presence of neural cells covering the inside of the PLGA tube guides did not make any difference in the functional recovery. By contrast, morphometric analysis showed that the introduction of N1E-115 cells inside PLGA 90:10 tube guides led to a significant lower number and size of regenerated nerve fibers, suggesting thus that this approach is not adequate for promoting peripheral nerve repair. Further studies are warranted to assess the role of other cellular systems as a foreseeable therapeutic strategy in peripheral nerve regeneration.
authors.affiliation: Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Universidade do Porto, Vairão, Portugal.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Luís
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Rodrigues
authors.forename: Stefano
authors.initials: S
authors.lastname: Geuna
authors.forename: Sandra
authors.initials: S
authors.lastname: Amado
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shirosaki
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Lee
authors.forename: Federica
authors.initials: F
authors.lastname: Fregnan
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lopes
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Veloso
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Ferreira
authors.forename: Jose D
authors.initials: JD
authors.lastname: Santos
authors.forename: Paulo A S
authors.initials: PA
authors.lastname: Armada-Da-silva
authors.forename: Artur S P
authors.initials: AS
authors.lastname: Varejão
authors.forename: Ana Colette
authors.initials: AC
authors.lastname: Maurício
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D016472:Motor Neuron Disease / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration; D009474:Neurons / Q000166:cytology*; D010146:Pain / Q000503:physiopathology; D011100:Polyglycolic Acid / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000473:pathology* / Q000503:physiopathology; D054457:Tissue Scaffolds; D014867:Water
chemical_list: D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid