Poly(alpha-hydroxyacids) for application in the spinal cord: resorbability and biocompatibility with adult rat Schwann cells and spinal cord.
Future surgical strategies to restore neurological function in the damaged human spinal cord may involve replacement of nerve tissue with cultured Schwann cells using biodegradable guiding implants. We have studied the in vitro and in vivo degradability of various aliphatic polyesters as well as their effects on rat Schwann cells in vitro and on spinal cord tissue in vivo. In vitro, cylinders made of poly(D,L-lactic-co-glycolic acid) 50:50 (PLA25GA50) started to degrade at 7 days, compared with 28 days for cylinders made of poly(D,L-lactic acid) (PLA50). This faster degradation of PLA25GA50 was reflected by a much higher absorption of water. In vivo, after implantation of PLA25GA50 or PLA50 cylinders between the stumps of a completely transected adult rat spinal cord, the decrease in molecular weight of both polymers was similar to that found in vitro. In vitro degradation of poly(L-lactic acid) (PLA100) mixed with increasing amounts of PLA100 oligomers also was determined. The degradation rate of PLA100 mixed with 30% oligomers was found to be similar to that of PLA50. In vitro, PLA25GA50 and the breakdown products had no adverse effect on the morphology, survival, and proliferation of cultured rat Schwann cells. In vivo, PLA25GA50 cylinders were integrated into the spinal tissue 2 weeks after implantation, unlike PLA50 cylinders. At all time points after surgery, the glial and inflammatory response near the lesion site was largely similar in both experimental and control animals. At time points later than 1 week, neurofilament-positive fibers were found within PLA25GA50 cylinders or the remains thereof. Growth-associated protein 43, which is indicative of regenerating axons, was observed in fibers in the vicinity of the injury site and in the remains of PLA25GA50 cylinders. The results suggest that poly(alpha-hydroxyacids) are likely candidates for application in spinal cord regeneration paradigms involving Schwann cells.
Gautier
S E
SE
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Florida 33136, USA.
Oudega
M
M
Fragoso
M
M
Chapon
P
P
Plant
G W
GW
Bunge
M B
MB
Parel
J M
JM
D000818:Animals; D001672:Biocompatible Materials; D001711:Biotransformation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D019344:Lactic Acid / Q000493:pharmacokinetics; D008264:Macrophages / Q000473:pathology; D009000:Monocytes / Q000473:pathology; D011100:Polyglycolic Acid / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology / Q000601:surgery*; D013119:Spinal Cord Injuries / Q000601:surgery; D013997:Time Factors
D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid