Coated electrospun alginate-containing fibers as novel delivery systems for regenerative purposes

Abstract

AimThe 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.MethodsMembranes 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.ResultsBoth 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.ConclusionThe 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.

Dual-Functioning Scaffolds for the Treatment of Spinal Cord Injury: Alginate Nanofibers Loaded with the Sigma 1 Receptor (S1R) Agonist RC-33 in Chitosan Films

“…The cross-linking process is responsible for a drastic reduction of fiber dimensions, attributable to the dissolution and removal of PEO and P407. These results are in line with our previous data [45]. Fiber size reduction leads to a contraction of fiber network with a consequent pore size decrease: 2.94 ± 0.200 µm and 1.45 ± 0.105 µm are the mean pore sizes of BLANK before and after cross-linking, respectively.…”

“…As for conductivity, a polymer solution lacking in charges does not produce fibers by electrospinning; an increase in electrical charge generally improves the elongation capability of the solution, favoring the formation of smaller diameter smooth fibers [48,50]. In a previous work of ours, a DoE approach was used to draw up guidelines for the preparation of mixtures of ALG with non-ionic polymers able to produce homogeneous nanofibers by electrospinning [45]. In particular, optimal values for viscosity at high shear rates, surface tension and conductivity were identified.…”

“…The cross-linking of BLANK and LOADED fibers was carried out according to a multistep protocol set up and described in [45]. Briefly, fibers were subjected to a pre-cross-linking treatment with absolute ethanol and, then, soaked in 2% w/w CaCl 2 ethanol/water solutions.…”

“…In an attempt to produce a drug delivery system that is flexible, easier to handle, and characterized by a controlled degradation rate and by peculiar surface properties, RC-33 loaded fibers were cross-linked with CaCl 2 aqueous solutions [45] and, then, incorporated in CS films. Chitosan was chosen in order to improve scaffold regenerative potential.…”

Sterilization of PAN/Gelatine Nanofibrous Mats for Cell Growth

“…Since the exact distribution of both components in fi bres has not been investigated yet, the infl uence of the fl uid culture medium on fi bre integrity has to be examined. Generally, nanofi brous mats prepared from biopolymers, such as gelatine or alginate, are known to support cell growth for wound healing, tissue engineering or biotechnological purposes [15][16][17][18][19]. Especially for elongated cells, such as neurites or fi broblasts, nanofi bres have been shown to support cell growth [20][21][22][23][24].…”