Coated electrospun alginate-containing fibers as novel delivery systems for regenerative purposes
Received 23 May 2018
Accepted for publication 17 July 2018
Published 17 October 2018 Volume 2018:13 Pages 6531—6550
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Farooq Shiekh
Peer reviewer comments 4
Editor who approved publication: Dr Thomas J Webster
Barbara Vigani,1 Silvia Rossi,1 Giuseppina Sandri,1 Maria Cristina Bonferoni,1 Giulia Milanesi,1 Giovanna Bruni,2 Franca Ferrari1
1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Department of Chemistry, University of Pavia, Pavia, Italy
Aim: The aim of the present work was to develop biodegradable alginate (ALG)-containing fibrous membranes intended for tissue repair, acting as both drug delivery systems and cell growth guidance.
Methods: Membranes were prepared by electrospinning. Since ALG can be electrospun only when blended with other spinnable polymers, dextran (DEX) and polyethylene oxide (PEO) were investigated as process adjuvants. ALG/DEX mixtures, characterized by different rheological and conductivity properties, were prepared in phosphate buffer or deionized water; surfactants were added to modulate polymer solution surface tension. The Design of Experiments (DoE) approach (full factorial design) was used to investigate the role of polymer solution features (rheological properties, surface tension, and conductivity) on electrospun fiber morphology. A high viscosity at 1,000 s-1 (1.3–1.9 Pa.s) or a high pseudoplasticity index (≥1.7), combined with a low surface tension (30–32 mN/m) and a low conductivity (800–1,000 µS/cm), was responsible for the production of ALG/DEX homogeneous fibers. Such ranges were successfully employed for the preparation of ALG-containing fibers, using PEO, instead of DEX, as process adjuvant. ALG/DEX and ALG/PEO fibers were subsequently subjected to cross-linking/coating processes to make them slowly biodegradable in aqueous medium. In particular, ALG/PEO fibers were cross-linked and coated with CaCl2/chitosan solutions in water/ethanol mixtures. Due to DEX high content, ALG/DEX fibers were soaked in a polylactide-co-glycolide (PLGA) solution in ethyl acetate.
Results: Both cross-linking and coating processes made fibers insoluble in physiological medium and produced an increase in their mechanical resistance, assessed by means of a tensile test. PLGA-coated ALG/DEX and chitosan-coated ALG/PEO fibers were biocompatible and able to support fibroblast adhesion.
Conclusion: The DoE approach allowed to draw up guidelines useful for the preparation of homogeneous fibers, starting from mixtures of ALG and non-ionic polymers. Such fibers, upon coating, resulted to be good cell substrates, allowing cell adhesion and growth.
Keywords: DoE approach, ALG-based fibers, rheological properties, conductivity, surface tension, chitosan, PLGA
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