Department of Drug Sciences, University of Pavia, Pavia, Italy,
Department of Chemistry, University of Pavia, Pavia, Italy.
Int J Nanomedicine. 2018 Oct 17;13:6531-6550. doi: 10.2147/IJN.S175069. eCollection 2018.
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.
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 (1.3-1.9 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 CaCl/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.
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.
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.
本工作旨在开发可生物降解的海藻酸钠(ALG)纤维膜,用于组织修复,作为药物输送系统和细胞生长指导。
通过静电纺丝制备膜。由于 ALG 只能与其他可纺聚合物混合纺丝,因此研究了葡聚糖(DEX)和聚氧化乙烯(PEO)作为加工助剂。ALG/DEX 混合物具有不同的流变和导电性特性,在磷酸盐缓冲液或去离子水中制备;添加表面活性剂来调节聚合物溶液的表面张力。采用实验设计(全因子设计)方法研究聚合物溶液特性(流变特性、表面张力和电导率)对静电纺纤维形态的影响。高粘度在 1000 s 时(1.3-1.9 Pa.s)或高假塑性指数(≥1.7),结合低表面张力(30-32 mN/m)和低电导率(800-1000 μS/cm),负责生产 ALG/DEX 均匀纤维。这些范围成功地用于制备含有 PEO 而不是 DEX 的 ALG 纤维,作为加工助剂。随后,将 ALG/DEX 和 ALG/PEO 纤维进行交联/涂层处理,使其在水性介质中缓慢生物降解。特别是,ALG/PEO 纤维在水/乙醇混合物中的 CaCl2/壳聚糖溶液中进行交联和涂层。由于 DEX 含量高,ALG/DEX 纤维在乙酸乙酯中的聚乳酸-共-羟基乙酸(PLGA)溶液中浸泡。
交联和涂层过程使纤维在生理介质中不溶,并通过拉伸试验评估其机械强度得到提高。PLGA 涂层的 ALG/DEX 和壳聚糖涂层的 ALG/PEO 纤维具有生物相容性,并能够支持成纤维细胞黏附。
实验设计方法为从 ALG 和非离子聚合物的混合物制备均匀纤维提供了有用的指导原则。经涂层后,这些纤维成为良好的细胞基质,允许细胞黏附和生长。