Human skin cell cultures onto PLA50 (PDLLA) bioresorbable polymers: influence of chemical and morphological surface modifications.
ABSTRACT Poly(alpha-hydroxy acid)s derived from lactic and glycolic acid are bioresorbable polymers which can cover a large range of thermal, physical, mechanical, and biological properties. Human keratinocytes have been shown as able to grow on a poly(DL-lactic acid) film. However the keratinocyte growth was delayed with respect to culture on standard tissue culture polystyrene, even though the same plateau level was observed after 2 weeks. In order to improve the performance of poly(DL-lactic acid) films as skin culture support, their surface was modified by creating tiny cavities using a method based on the leaching out of poly(ethylene oxide) from poly(lactic acid)-poly(ethylene oxide) heterogeneous blends. The surface of the films was also chemically modified by alkaline attack with sodium hydroxide and by type-I collagen coating. Murine fibroblast cell line and primary cultures of human fibroblasts and of two types of keratinocytes were allowed to adhere and to grow comparatively on the different films. The presence of cavities affected neither the adhesion of dermal fibroblasts nor that of keratinocytes. Only keratinocyte proliferation was significantly reduced by the presence of cavities. Collagen coating improved skin cell adhesion and proliferation as well, except in the case of murine fibroblasts. In the case of the NaOH treatments, similar trends were observed but their extent depended on the treatment time. In the case of chemical modifications, fluorescence microscopy bore out adhesion and proliferation tendencies deduced from MTT tests.
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ABSTRACT: Polymer micelles with two different core-forming blocks, poly(d,l -lactide) (PLA) and poly(epsilon-caprolactone) (PCL), but the same coronal material, poly(ethylene glycol) (PEG), were investigated in this study as nanoscopic drug carriers. The release of two different drugs, doxorubicin (DOX) and beta-lapachone (beta-lap), from PEG(5k)-b-PCL(5k) and PEG(5k)-b-PLA(5k) micelles was studied at pH 5.0 and 7.4. Mathematical solutions of both Higuchi's model and Fickian diffusion equations were utilized to elucidate the differences between the micelle core materials for the two drugs. The neutral and smaller of the two drugs tested, beta-lap, demonstrated faster, pH-independent release, suggesting that no substantial changes occurred in either micelle core at lower pH. In contrast, the release rate of DOX was found to noticeably increase at lower pH with a larger cumulative amount of drug released. Different core materials were shown to have considerable influence on the release kinetics of both drugs: in both cases, the more hydrophobic PCL core showed slower drug release rates compared with the less hydrophobic PLA core.Experimental Biology and Medicine 10/2007; 232(8):1090-9. · 2.80 Impact Factor
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ABSTRACT: Over the last years, increasing attention has been paid to skin engineering due to its predominant function in body integrity. Thus, many laboratories are attempting to develop a dermal–epidermal complex. The aim of this study was to evaluate the potential of poly(α-hydroxyacid)s in the development of biocompatible and bioresorbable dermal scaffold combining human fibroblasts and keratinocytes, in order to obviate the drawbacks of using natural polymers such as collagen, hyaluronic acid and fibrin. We first confirmed the interest of poly(d,l-lactic acid) (PLA50) during the reconstitution of epidermis and next, we investigated the potential of poly(d,l-lactic acid)-poly(ethylene glycol)-poly(d,l-lactic acid) (PLA50-PEG-PLA50) for either skin cytocompatibility or scaffold processing. Data showed that PLA50-PEG-PLA50 is compatible with the culture of human skin cells (fibroblasts and keratinocytes) and the development of a porous scaffold; two requirements compulsory for being considered as an adequate skin substitute. In fine, this material could represent the first generation of new skin dressings, i.e. a new concept taking advantage of both implantable devices and current dressings.Annales Pharmaceutiques Françaises. 01/2008; 66(s 5–6).
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ABSTRACT: In poly(DL-lactic acid)-cholesterol oligomers (LC), a novel cholesterol modified poly(DL-lactic acid) (PLA), was synthesized via bulk polymerization of DL-lactide using cholesterol initiator. Gel permeation chromatography (GPC) and 1H nuclear magnetic resonance spectroscopy (1H-NMR) results indicated a narrow molecular weight distribution of poly (DL-lactic acid)-cholesterol oligomers (LC). Mouse MC3T3 osteoblast-like cells were selected as a model system to test the cell behavior of cholesterol modified PLA substrates. The osteoblast attachment, proliferation, and viability revealed that the cholesterol modified PLA was significantly osteoblast compatible and may have potential as a bone tissue engineering material.Journal of Bioactive and Compatible Polymers - J BIOACT COMPAT POLYM. 01/2005; 20(6):527-540.