Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vi...Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking,halting the discovery of new drugs.Here,we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling.This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM.After modeling OM with all pro-inflammatory hallmarks,we were able to suppress OM with our in-house plant-produced epidermal growth factor(P-EGF),a well-known re-epithelialization cue.Thus,this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection.This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.展开更多
基金funded by the National Research Council of Thailand(NRCT)and Chulalongkorn University with project number:N42A670176 to JNF(main PI)and to RC(Co-I)supported by the International Association for Dental,Oral and Craniofacial Research(IADR)2022 Innovation in Oral Care Award funded by GlaxoSmithKline to JNF,CHLH,KST,SY and WP+5 种基金supported by Thailand Science Research and Innovation Fund Chulalongkorn University to JNFRC.Center of Excellence and Innovation for Oral Health and Healthy Longevity is funded by the Ratchadaphiseksomphot Endowment Fund,Chulalongkorn University(Grant number:CE68_003_3200_001)supported by a Chulalongkorn University scholarship from Graduate Scholarship Program for ASEAN or Non-ASEAN Countriessupported by the 90th Anniversary of Chulalongkorn University Scholarship under Ratchadapisek Somphot Endowment Fund(Grant number:GCUGR1125662098M)the IADR-Southeast Asia Mentor-Mentee Funding provided to TTTT under the mentorship of JNF and OMsupported by the Second Century Fund(C2F),Chulalongkorn University provided to TVP.
文摘Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking,halting the discovery of new drugs.Here,we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling.This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM.After modeling OM with all pro-inflammatory hallmarks,we were able to suppress OM with our in-house plant-produced epidermal growth factor(P-EGF),a well-known re-epithelialization cue.Thus,this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection.This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.
