In vitro and in vivo testing of nanofibrous membranes doped with alaptide and L-arginine for wound treatment
Language English Country Great Britain, England Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Arginine chemistry MeSH
- Biocompatible Materials chemistry MeSH
- Peptides, Cyclic chemistry MeSH
- Electrochemistry MeSH
- Electrodes MeSH
- Fibroblasts drug effects MeSH
- Microscopy, Fluorescence MeSH
- Wound Healing drug effects MeSH
- Rats MeSH
- Skin pathology MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Nanofibers chemistry MeSH
- Neuropeptides chemistry MeSH
- Peptides chemistry MeSH
- Rats, Wistar MeSH
- Cell Proliferation MeSH
- Spectrum Analysis, Raman MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- In Vitro Techniques MeSH
- Materials Testing MeSH
- Tissue Engineering methods MeSH
- Tissue Scaffolds chemistry MeSH
- Chromatography, High Pressure Liquid MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Arginine MeSH
- Biocompatible Materials MeSH
- cyclo(alanine-(1-amino-1-cyclopentane)carbonyl) MeSH Browser
- Peptides, Cyclic MeSH
- Neuropeptides MeSH
- Peptides MeSH
We have prepared a candidate biocompatible construct for skin wound healing based on electrospun polycaprolactone (PCL) nanofibrous membranes. The membrane material was loaded either with L-arginine or with alaptide, or with a mixture of both bioactive components. Alaptide is a spirocyclic synthetic dipeptide, an analogue of melanocyte-stimulating hormone release-inhibiting factor. L-arginine is an amino acid with a basic guanidine side chain. It is a direct precursor of nitric oxide, which plays a pivotal role in skin repair. The presence and the distribution of the additives were proved with high-performance liquid chromatography, Fourier-transform infrared spectroscopy and Raman spectroscopy. The influence of L-arginine and alaptide on the morphology of the membrane was characterized using scanning electron microscopy. No statistically significant correlation between fiber diameter and drug concentration was observed. The membranes were then tested in vitro for their cytotoxicity, using primary human dermal fibroblasts, in order to obtain the optimal concentrations of the additives for in vivo tests in a rat model. The membranes with the highest concentration of L-arginine (10 wt. %) proved to be cytotoxic. The membranes with alaptide in concentrations from 0.1 to 2.5 wt.%, and with the other L-arginine concentrations (1 and 5 wt.%), did not show high toxicity. In addition, there was no observed improvement in cell proliferation on the membranes. The in vivo experiments revealed that membranes with 1.5 wt.% of alaptide or with 1.5 wt.% of alaptide in combination with 5 wt.% of L-arginine markedly accelerated the healing of skin incisions, and particularly the healing of skin burns, i.e. wounds of relatively large extent. These results indicate that our newly-developed nanofibrous membranes are promising for treating wounds with large damaged areas, where a supporting material is needed.
1st Faculty of Medicine Charles University Prague Czech Republic
Author to whom any correspondence should be addressed
Department of Chemistry Technical University of Liberec Liberec Czech Republic
Institute of Physiology of the Czech Academy of Sciences Prague Czech Republic
University of Chemistry and Technology Prague Czech Republic
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