Enhanced peripheral nerve regeneration elicited by cell-mediated events delivered via a bioresorbable PLGA guide.
Using an established rat peripheral-nerve regeneration model, the authors have demonstrated enhancement of regeneration following subcutaneous priming of bioresorbable poly(lactic-co-glycolic)acid (PLGA) guides in vivo. Four weeks after nerve reconstruction, regeneration of the peripheral nerve through the cell-infiltrated guides displayed a significant increase in the total axon number and myelination status recorded in primed over unprimed guides, demonstrating the importance of cell-mediated events in the regeneration process. To define the different components enhancing nerve regeneration in this model, they have focused on identifying factors capable of eliciting Schwann-cell migration, since this has been identified as an early and necessary event in nerve regeneration. Using an in vitro migration assay, screening of a limited number of cellular and extracellular factors has demonstrated differential promotion of Schwann-cell migration. Of interest, combining fibronectin and bFGF resulted in a two-fold enhancement in Schwann-cell migration over that recorded with either alone. These results describe a rapid screening process for identifying various molecules and combinations thereof, with potential involvement in Schwann-cell migration. Coupling these findings to the use of the PLGA guide as an in vivo delivery system provides a rationale for the selection of exogenous factors to test for the enhancement of peripheral-nerve regeneration.
Bryan
David J
DJ
Tissue Engineering Laboratory, Research and Education Institute, Lahey Clinic, Burlington, Massachusetts 01805, USA.
Tang
Jin Bo
JB
Holway
Antonia H
AH
Rieger-Christ
Kimberly M
KM
Trantolo
Debra J
DJ
Wise
Donald L
DL
Summerhayes
Ian C
IC
D000818:Animals; D001672:Biocompatible Materials; D002465:Cell Movement; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D010525:Peripheral Nerves / Q000473:pathology*; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000494:pharmacology*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012583:Schwann Cells / Q000637:transplantation*; D012584:Sciatic Nerve / Q000502:physiology* / Q000601:surgery*; D012680:Sensitivity and Specificity
D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid