Development of microspheres for biomedical applications: a review

Abstract

An overview of microspheres manufactured for use in biomedical applications based on recent literature is presented in this review. Different types of glasses (i.e. silicate, borate, and phosphates), ceramics and polymer-based microspheres (both natural and synthetic) in the form of porous , non-porous and hollow structures that are either already in use or are currently being investigated within the biomedical area are discussed. The advantages of using microspheres in applications such as drug delivery, bone tissue engineering and regeneration, absorption and desorption of substances, kinetic release of the loaded drug components are also presented. This review also reports on the preparation and characterisation methodologies used for the manufacture of these microspheres. Finally, a brief summary of the existing challenges associated with processing these microspheres which requires further research and development are presented.

Keywords: Ceramics; Glasses; Microspheres; Polymers; Porous; Tissue engineering and regenerative medicine.

Fig. 1

Scheme of production of glass microspheres via a Sol–gel, b flame spheroidisation and c tube furnace methods

Fig. 2

Real-time video microscopy image showing non-uniform reaction of Dysprosium Lithium-Borate glass microspheres in PBS solution at 37 °C (Conzone et al. 2004)

Fig. 3

Schematic illustration showing mechanism for production of hollow, porous HAP microspheres (Wang et al. 2007)

Fig. 4

Weight loss of 45S5 glass–ceramic microspheres observed over a period of 4 weeks in 1.0 M K₂HPO₄ solution (Fu et al. 2012)

Fig. 5

SEM image of a phosphate glass microspheres produced using flame spheroidisation process and b microspheres after 21 days of immersion in simulated body fluid (SBF) at 37 °C a MVP9c and b MVP3 microspheres (Sene et al. 2008)

Fig. 6

a SEM, and b scanning laser confocal microscopy (SLCM) images of titanium phosphate glass microspheres cultured with MG63 cells on day 7. Scale bar of SEM image represents 25 μ (Lakhkar et al. 2012)

Fig. 7

SEM images of calcium-titanium-phosphate (CTP) microspheres a Non-sintered CTP microspheres and b sintered CTP microsphere Ribeiro et al. (2006)

Fig. 8

a SEM image of 5 % GEL/OF 900, b Morphology of Saos-2 cells on gelatin/hydroxyapatite microspheres and c after 14 days of culture Perez et al. (2011)

Fig. 9

Typical schemes of production of polymer microspheres employing various methods a emulsion-solvent evaporation, b sol-spray drying and c electro-spinning processes

Fig. 10

SEM images of a PLLA microspheres, b gamma-irradiated PLLA microspheres, c Ho-PLLA microspheres and d gamma-irradiated Ho-PLLA microspheres after 52 weeks of incubation in phosphate buffer. Scale bars represent 20 μ (Zielhuis et al. 2006)

Fig. 11

SEM images of PLA microspheres produced using emulsion-solvent evaporation process a surface morphology, and b internal cross-section image (Hong et al. 2005)

Fig. 12

SEM micrographs of a PCL microspheres, obtained by single emulsion, b photograph of PCL microspheres sintered scaffold (Luciani et al. 2008)

Fig. 13

SEM images of a PCL microspheres produced using electrospraying process (Flow rate 0.2 mL/h, tip-to-collector distance 25 cm and voltage 16 kV). Scale bar represents 100 μ (Bock et al. 2011), and b PCL microspheres prepared using polymer blend melt technique (Lin et al. 1999)

Fig. 14

a SEM images of porous PLGA microspheres with small and b large pores (Choi et al. 2010)

Fig. 15

a SEM image of chitosan microspheres obtained by spray drying process Tao et al. (2013), b alginate microspheres prepared using emulsification technique (scale bar 62.5 µm) (Lemoine et al. 1998), c bright-field image of collagen microspheres in mineral oil produced via emulsification process (scale bar 200 µm) (Hong et al. 2012), and d protein microspheres prepared by ultrasonication (Han et al. 2008)