title: Preparation and characterization of structured hydrogel microparticles based on cross-linked hyperbranched polyglycerol.
abstract: The aim of this work was to obtain well-defined HyPG-MA (methacrylated hyperbranched polyglycerol) microparticles with uniform sizes. Therefore, three different preparation methods were evaluated. First, we assessed a micromolding technique using rigid SU-8 (a photoresist based on epoxies) grids. Independent of the surface treatment of the SU-8 grid or the type of polymer used, approximately 50% of the microgels remained attached to the SU-8 grid or broke into smaller particles during the release process in which drying of the gels was followed by a sonication process. Although 90% methacrylate conversion could be obtained, this method has some additional drawbacks as the obtained dried microgels did not rehydrate completely after the drying step. Second, a soft micromolding technique was evaluated using elastomeric PDMS (poly(dimethyl siloxane)) grids. The use of these flexible grids resulted in a high yield (80-90% yield; >90% methacrylate conversion) of microgels with a well-defined size and shape (squares 100 microm x 100 microm x 50 microm or hexagons with Ø 30 microm and a thickness of 20 microm) without the occurrence of water evaporation. However, a number of particles showed a less-defined shape as not all grids could be filled well. The microgels showed restricted swelling, implying that these gels are dimensionally stable. Third, an alternative method referred to as photolithography was evaluated. This method was suitable to tailor accurately the size and shape of HyPG-MA microgels and additionally gained 100% yield. Well-defined HyPG-MA microgels in the size range of 200-1400 microm (thickness of 6, 20, or 50 microm), with a methacrylate conversion of >90%, could easily be prepared by adding an inhibitor (e.g., 1% (w/v) of vitamin C) to the polymer solution to inhibit dark polymerization. Microgels in the size range of 30-100 microm (>90% conversion) could only be obtained when applying the photomask in direct contact with the polymer solution and using a higher (i.e., 2% (w/v)) concentration of vitamin C. Additionally, the microgels showed limited swelling, indicating that rather dimensionally stable particles were obtained. In conclusion, this paper shows that photolithography and soft micromolding, as compared to rigid micromolding, are the most appropriate techniques to fabricate structured HyPG-MA microgels with a tailorable and well-defined size and shape. These microgels have great potential in tissue engineering and drug delivery applications.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Marion H M
authors.initials: MH
authors.lastname: Oudshoorn
authors.forename: Roel
authors.initials: R
authors.lastname: Penterman
authors.forename: Robert
authors.initials: R
authors.lastname: Rissmann
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Broer
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D020724:Elastomers; D004852:Epoxy Compounds / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry*; D020100:Hydrogels / Q000138:chemical synthesis*; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry*; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010777:Photochemistry; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004129:Dimethylpolysiloxanes; D020724:Elastomers; D004852:Epoxy Compounds; D020100:Hydrogels; D008689:Methacrylates; D011108:Polymers; C520895:SU-8 compound; C036925:elastomeric polymer; C043941:polyglycerol; D005990:Glycerol