Date Published: April 15, 2017
Author(s): Abdulrahman Baki, Cheryl V. Rahman, Lisa J. White, David J. Scurr, Omar Qutachi, Kevin M. Shakesheff.
Schematic figure showing the methods used to prepare Fit-C labelled gel-MA and the different surface treatment approaches used to modify the surface of PdlLGA microspheres with it.
Injectable PdlLGA microspheres have been proposed as cell delivery systems as they can form porous scaffolds , ,  and control the release of signalling molecules into the cell niche , , , . However, PdlLGA microspheres have limited reactive groups, such as carboxyl groups, available on the surface; this may limit the potential for further grafting of molecules required to support cell attachment and proliferation , . To overcome this limitation, different approaches have been proposed to functionalise the surface and to enable further grafting , .
PdlLGA microspheres offer a potential injectable cell delivery system with controllable growth factor release for different tissue engineering applications , , , . However, as with other polyester polymers, PdlLGA have limited functional groups on the surface which limit grafting of tissue specific bioactive molecules to control cell behaviour. This study has proposed modifying the surface of PdlLGA microspheres with gel-MA to enable grafting of further tissue specific biomolecules through the methacrylate group without compromising surface biocompatibility. Gel-MA molecules have the potential to form hydrogels with tunable elastic properties upon photo-crosslinking. Unlike gelatine, gel-MA molecules contain the methacrylate vinyl groups which can be used to further graft gel-MA or other bioactive molecules containing vinyl groups , . Moreover, non-crosslinked gelatine hydrogels dissolve over 24 h of incubation at 37 °C while gel-MA hydrogels prepared using UV photo-crosslinking offer controllable elastic properties and do not dissolve over 24 h of incubation at 37 °C (Supplementary Data 11).
This study has evaluated three different approaches to modify the surface of PdlLGA microspheres with gel-MA: surface adsorption, surface entrapment, and oxygen plasma treatment. Different surface analytical and quantitative assays have shown that the oxygen plasma treatment approach produced the highest density of gel-MA on the surface of modified PdlLGA microspheres followed by entrapment and adsorption approaches respectively. Moreover, different microscopy images have shown porous structures inside PdlLGA microspheres modified using surface entrapment approach. This may suggest a deep penetration of gel-MA molecules underneath the surface of microspheres and a possible restructuring of the polymer microsphere during the process. On the other hand, the significant increase in cell metabolic activity of immortalised hMSCs cultured for 72 h on the surface of plasma and entrapment modified microspheres compared to adsorption and non-modified microspheres can be related to the gel-MA content on the surface. This in turn would suggest no adverse effects of the proposed surface modification approaches on the biocompatibility of the system.