Heparin-conjugated alginate multilayered microspheres for controlled release of bFGF

Abstract

In order to effectively immobilize and control release of basic fibroblast growth factor (bFGF) from alginate microspheres, heparin-conjugated alginate (H-Alg) was first synthesized by covalent binding. Then multilayered H-Alg microspheres (multilayered microspheres) were fabricated via an electrostatic droplet generation technique followed by a layer-by-layer (LbL) self-assembly technique. Several techniques such as Fourier transform infrared spectroscopy (FTIR), (1)H-NMR, zeta potential analysis and scanning electron microscopy (SEM) were used to characterize the properties of H-Alg (FTIR and (1)H-NMR) and multilayered microspheres (FTIR, zeta potential analysis and SEM). bFGF binding efficiency, release profiles of bFGF from multilayered microspheres and the biological activity of released bFGF were well investigated. It was found that the bFGF binding efficiency of H-Alg microspheres was increased up to five times higher than that of the alginate microspheres. Additionally, the release profiles of bFGF from multilayered microspheres were sustained for two weeks with relieved initial burst release, and the release rate to bFGF could be regulated by controlling the number of deposited layers. Importantly, the released bFGF still retained its biological activity as assessed by the in vitro proliferation of NIH-3T3 mouse fibroblasts. In conclusion, this study presented an easy yet effective method for the controlled, sustained release of heparin-binding growth factors, using polyelectrolyte multilayer-coated heparin-conjugated alginate microspheres.

Multilayered pore‐closedPLGAmicrosphere deliveringOGPandBMP‐2 in sequential release patterns for the facilitation ofBMSCs osteogenic differentiation

“…To account for the higher surface‐area‐to‐volume ratio in the microsphere system, we also deposited two bilayers of HA‐CS to ensure uniform coverage before deposition of Hep and BMP‐2. In fact, it has been reported that this method of coupling proteins by LbL assembly can not only effectively decrease the diffusion of factors through layers, but also prolong their half‐life and maintain their bioactivity …”

Bioengineering a pre-vascularized pouch for subsequent islet transplantation using VEGF-loaded polylactide capsules

“…− at 1010 cm −1 , symmetrical stretching of SvO in NH-SO 3 − at 1220 cm −1 , N-H bending at 1420 cm −1 , CvO stretching at 1610 cm −1 and OH stretching at 3400 cm −1 . 46 Most of these peaks were found in both the PA-H-PLCL and CL-H-PLCL samples; however, in contrast to PA-H-PLCL, the chemically crosslinked CL-H-PLCL exhibited a new peak at 1640 cm −1 that was characteristic of the amide bond created as a result of the covalent crosslinking between heparin and aminated PLCL. Our data are consistent with an earlier report by Singh et al, who observed a similar peak after chemical crosslinking of heparin and PCL.…”

Effect of heparin and peptide conjugation on structure and functional properties of alginate in solutions and hydrogels

“…Diffusion of the growth factors through the clusters may be inhibited due to the high polymer density, explaining why even though the gel disintegrates, the release profile is very slow. Synthesis of Alg-Hep conjugation of heparin to alginate was performed following the literature 42 with some modifications. To minimize hydrolysis of EDC, the reaction was carried out in a 0.1 M buffer of 2-morpholinoethane sulfonic acid (MES buffer).…”