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A simple technique for development of fibres with programmable microsphere concentration gradients for local protein delivery

Mehrpouya, Fahimeh, Yue, Zhilian, Romeo, Tony, Gorkin, Robert, Kapsa, Robert M. I., Moulton, Simon E., Wallace, Gordon G.
Journal of materials chemistry B 2019 v.7 no.4 pp. 556-565
alginates, bioactive compounds, bovine serum albumin, chemotaxis, fluorescein, hydrogels, microparticles, models, polymers, tissue repair
Alginate has been a biologically viable option for controlled local delivery of bioactive molecules in vitro and in vivo. Specific bioactive molecule release profiles are achieved often by controlling polymer composition/concentration, which also determines the modulus of hydrogels. This largely limits alginate-mediated bioactive molecule delivery to single-factors of uniform concentration applications, rather than applications that may require (multiple) bioactive molecules delivered at a concentration gradient for chemotactic purposes. Here we report a two-phase PLGA/alginate delivery system composed of protein-laden poly-d,l-lactic-co-glycolic acid (PLGA) microspheres wet-spun into alginate fibres. Fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) was used as a model protein and the developed structures were characterized. The fabrication system devised was shown to produce wet-spun fibres with a protein concentration gradient (G-Alg/PLGA fibre). The two-phase delivery matrices display retarded FITC-BSA release in both initial and late stages compared to release from the PLGA microspheres or alginate fibre alone. In addition, incorporation of higher concentrations of protein-loaded PLGA microspheres increased protein release compared to the fibres with lower concentrations of BSA-loaded microspheres. The “programmable” microsphere concentration gradient fibre methodology presented here may enable development of novel alginate scaffolds with the ability to guide tissue regeneration through tightly-controlled release of one or more proteins in highly defined spatio-temporal configurations.