title: Microfluidics-assisted fabrication of gelatin-silica core-shell microgels for injectable tissue constructs.
abstract: Microfabrication technology provides a highly versatile platform for engineering hydrogels used in biomedical applications with high-resolution control and injectability. Herein, we present a strategy of microfluidics-assisted fabrication photo-cross-linkable gelatin microgels, coupled with providing protective silica hydrogel layer on the microgel surface to ultimately generate gelatin-silica core-shell microgels for applications as in vitro cell culture platform and injectable tissue constructs. A microfluidic device having flow-focusing channel geometry was utilized to generate droplets containing methacrylated gelatin (GelMA), followed by a photo-cross-linking step to synthesize GelMA microgels. The size of the microgels could easily be controlled by varying the ratio of flow rates of aqueous and oil phases. Then, the GelMA microgels were used as in vitro cell culture platform to grow cardiac side population cells on the microgel surface. The cells readily adhered on the microgel surface and proliferated over time while maintaining high viability (∼90%). The cells on the microgels were also able to migrate to their surrounding area. In addition, the microgels eventually degraded over time. These results demonstrate that cell-seeded GelMA microgels have a great potential as injectable tissue constructs. Furthermore, we demonstrated that coating the cells on GelMA microgels with biocompatible and biodegradable silica hydrogels via sol-gel method provided significant protection against oxidative stress which is often encountered during and after injection into host tissues, and detrimental to the cells. Overall, the microfluidic approach to generate cell-adhesive microgel core, coupled with silica hydrogels as a protective shell, will be highly useful as a cell culture platform to generate a wide range of injectable tissue constructs.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Cambridge, Massachusetts 02139, United States.
authors.forename: Chaenyung
authors.initials: C
authors.lastname: Cha
authors.forename: Jonghyun
authors.initials: J
authors.lastname: Oh
authors.forename: Keekyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Yiling
authors.initials: Y
authors.lastname: Qiu
authors.forename: Maria
authors.initials: M
authors.lastname: Joh
authors.forename: Su Ryon
authors.initials: SR
authors.lastname: Shin
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Gulden
authors.initials: G
authors.lastname: Camci-Unal
authors.forename: Kai-tak
authors.initials: KT
authors.lastname: Wan
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry*; D005782:Gels; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D005782:Gels; D012822:Silicon Dioxide; D005780:Gelatin