Optimised production of multifunctional microfibres by microfluidic chip technology for tissue engineering applications

Abstract

This paper describes a method for the production of alginate microfibres using glass-based microfluidic chips fabricated by a photolithography-wet etching procedure. The main focus of the work is the fabrication of a cell containing multifunctional microfibres which have great potential for applications in drug release formulations and tissue engineering scaffolds (to guide the regeneration of tissues in predefined sizes and shapes) providing cell structural support and immunoisolation. The key parameters, which critically influence the formation of microfibres and their geometries, were identified by a classical intuitive approach COST (Changing One Separate factor a Time). In particular, their effects on the microfibre diameter were investigated, which are directly associated with their functionalities relating to the implantation site, the nutrient availability and diffusion/transport of oxygen, essential nutrients, growth factors, metabolic waste and secretory products. The interplay between the alginate solution concentration, pumping rate and gelling bath concentration in controlling the diameter of the produced microfibres was investigated with a statistical approach by means of a "design of the experiments" (DoEs) optimization and screening. Finally, the processing impacts on cell viability, the cellular effect of wall thickness consistency and the spatial distribution of cells within the alginate microfibre were examined. We provide an approach for the production of alginate microfibres with controlled shape and content, which could be further developed for scaling up and working towards FDA approval.

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

“…28 Microfluidic-based systems offer advantages over conventional bench systems in terms of performance, reduced sample/solvent quantity, automation, and fine regulation of the boundary conditions. 29,30 The micro-scale, in which fluidics is restricted to laminar flow and diffusive mixing, allows precise control of the physical parameters within the fluidic environment. In addition, coupling with microscope-based imaging techniques, provides a platform for in situ analysis of individual cells exposed to US or other physico-chemical stimuli.…”

Fiber-based tissue engineering: Progress, challenges, and opportunities

“…Microfluidic spun fibers have been formed using various polymers such as alginate (Mazzitelli et al, 2011, Su et al, 2008, Yamada et al, 2012), chitosan, poly(lactic-co-glycolic acid) (PLGA) (Hwang et al, 2009, Hwang, Khademhosseini, 2008), and chitosan/alginate (Lee, Lee, 2011a). A rotating roller can be used to collect the fabricated fibers and to form scaffolds containing aligned fibers (Hwang, Park, 2009, Hwang, Khademhosseini, 2008, Su, Zheng, 2008).…”

“…Incorporation of living cells in fibers fabricated using microfluidic spinning systems has been demonstrated by several researchers (Hwang, Park, 2009, Lee, Lee, 2011a, Mazzitelli, Capretto, 2011, Shin et al, 2007, Su, Zheng, 2008, Yamada, Sugaya, 2012). For example, Shin et al encapsulated human fibroblast cells in calcium alginate fibers and demonstrated that the cells remained viable after seven days of culture.…”

Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

“…The channels had a semicircular cross-sectional shape so that channel width was strictly connected with channel depth, due to the isotropicity of the fabrication procedure. 34,35 The flow within the microchannels was monitored by an inverted microscope (IX51; Olympus Corporation, Tokyo, Japan). PMs were also prepared by bulk mixing.…”

“…34 Firstly, the channel pattern was designed by AutoCAD ® drawing software (Autodesk, Inc, San Rafael, CA), thereafter, a negative film representing the optical mask was obtained by a commercial photomask producer (JD Photo-Tools, Oldham, Lancashire, United Kingdom). Crown white glass (B-270) plates (thickness of 1.5 mM) coated with a thin layer of chromium metal mask plus an upper layer of positive photoresist (AZ 1500; Telic Company, Valencia, CA) were used for channel network fabrication.…”