Growth of various cell types in the presence of lactic and glycolic acids: the adverse effect of glycolic acid released from PLAGA copolymer on keratinocyte proliferation.
Poly(alpha-hydroxy-acid)s derived from lactic acid (LA) and glycolic acid (GA) are bioresorbable polymers that are currently used in human surgery and in pharmacology to make temporary therapeutic devices. Nowadays, increasing attention is paid to these polymers in the field of tissue engineering. However, the literature shows that a large number of factors can affect many of their properties and the responses of biological systems. As part of our investigation of the biocompatibility of degradable aliphatic polyesters, the effects of LA and GA on the proliferation of various cells under in vitro cell culture conditions were studied. The release of LA and GA from films made of a copolymer synthesized by the zinc lactate method and composed of 37.5% L-lactyl, 37.5% D-lactyl, and 25% glycolyl repeating units was first investigated over a period of 30 days under abiotic conditions in a cell culture medium in order to identify a range of acid concentrations consistent with releases to be expected in real cell cultures. Four cell lines, namely 3T3-J2, C3H10(1/2), A431, and HaCat, and three primary cell cultures, namely rat endothelial cells, rat smooth muscle cells, and human dermal fibroblasts, were then allowed to grow in the presence of LA and GA at various concentrations taken within the selected 10-1000 mg/cm3 range. Little or no effect was observed on the proliferation of all cells except human keratinocytes, whose growth was dramatically inhibited by GA at concentrations as low as 10 mg/cm3. The inhibiting effect of GA was confirmed by considering the growth of keratinocytes on films made of the same copolymer, in comparison with poly(DL-lactic acid) and polystyrene taken as references. This work shows that GA-releasing degradable matrices are not adapted to the culture of keratinocytes with the aim of making skin grafts.
Garric
Xavier
X
CRBA, UMR CNRS 5473, University Montpellier 1, Faculty of Pharmacy, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France. xgarric@iurc.montp.inserm.fr
Molès
Jean-Pierre
JP
Garreau
Henri
H
Braud
Christian
C
Guilhou
Jean-Jacques
JJ
Vert
Michel
M
D000818:Animals; D001672:Biocompatible Materials; D018929:Cell Culture Techniques; D002455:Cell Division; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006016:Glycolates / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D019344:Lactic Acid / Q000494:pharmacology*; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
D001672:Biocompatible Materials; D006016:Glycolates; C031149:glycolic acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid