title: The effect of surface modification of mesoporous silica micro-rod scaffold on immune cell activation and infiltration.
abstract: Biomaterial scaffold based vaccines show significant potential in generating potent antigen-specific immunity. However, the role of the scaffold surface chemistry in initiating and modulating the immune response is not well understood. In this study, a mesoporous silica micro-rod (MSR) scaffold was modified with PEG, PEG-RGD and PEG-RDG groups. PEG modification significantly enhanced BMDC activation marker up-regulation and IL-1β production in vitro, and innate immune cell infiltration in vivo. PEG-RGD MSRs and PEG-RDG MSRs displayed decreased inflammation compared to PEG MSRs, and the effect was not RGD specific. Finally, the Nlrp3 inflammasome was found to be necessary for MSR stimulated IL-1β production in vitro and played a key role in regulating immune cell infiltration in vivo. These findings suggest that simply modulating the surface chemistry of a scaffold can regulate its immune cell infiltration profile and have implications for the design and development of new material based vaccines.
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: Weiwei Aileen
authors.initials: WA
authors.lastname: Li
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: Beverly Ying
authors.initials: BY
authors.lastname: Lu
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: Luo
authors.initials: L
authors.lastname: Gu
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Choi
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Jaeyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA. Electronic address: mooneyd@seas.harvard.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D058847:Inflammasomes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D012822:Silicon Dioxide
keywords: Acute inflammation; Inflammasome; Mesoporous silica; Poly(ethylene glycol); RGD