Manipulating the release of growth factors from biodegradable microspheres for potentially different therapeutic effects by using two different electrospray techniques for microsphere fabrication

Appropriate administration of growth factors is of great importance for directing cell behavior in regenerative medicine, which usually needs suitable carriers to protect the growth factors and to control their releases in specific spatiotemporal manners. Electrospray techniques, particularly emulsion electrospray and coaxial electrospray, have been proven effective to generate capsular/core-shell structured microspheres for growth factor delivery with superior convenience and high bioactivity retention. However, the difference in the release behavior of growth factors from emulsion electrosprayed microspheres and coaxial electrosprayed microspheres remains ambiguous, which causes the difficulty in selecting appropriate approach for certain growth factor-based therapy. In our investigation, vascular endothelial growth factor (VEGF) was used as a model molecule to be encapsulated in the microspheres prepared respectively by emulsion electrospray and coaxial electrospray using the same biodegradable poly(lactic-co-glycolic acid) (PLGA) polymer, for which size distribution, structure, morphology and in vitro degradation properties were studied and found to be tunable by different electrospray techniques. PLGA microspheres fabricated by emulsion electrospray presented nanoporous surface morphology and interior multi-compartment cores, resulting in sustained VEGF release. In comparison, the microspherical vehicles made by coaxial electrospray showing golf-ball-like textured surface morphology and interior monolithic cores led to initial fast release of VEGF. Vascular endothelial cells responded differently under the stimuli of locally released VEGF from different types of electrosprayed PLGA microspheres. The underlying mechanisms for different release behaviors of the encapsulated growth factors that were affected by microspherical vehicles formed by different electrospray techniques were presented, which would offer the design rationale for growth factor delivery vehicles with specific release kinetics, suiting for different therapeutic purposes.