Nanotherapeutics for regeneration of degenerated tissue infected by bacteria through the multiple delivery of bioactive ions and growth factor with antibacterial/angiogenic and osteogenic/odontogenic capacity  

作　　者：Ahmed El-Fiqi Nandin Mandakhbayar Seung Bin Jo Jonathan C.Knowles Jung-Hwan Lee Hae-Won Kim 

机构地区：[1]Institute of Tissue Regeneration Engineering(ITREN),Dankook University,Cheonan,31116,Republic of Korea [2]Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine,Dankook University,Cheonan,31116,Republic of Korea [3]Glass Research Department,National Research Centre,Cairo,12622,Egypt [4]Division of Biomaterials and Tissue Engineering,UCL Eastman Dental Institute,256 Grays Inn Road,London,WC1X 8LD,UK [5]The Discoveries Centre for Regenerative and Precision Medicine,UCL Campus,London,UK [6]Department of Biomaterials Science,School of Dentistry,Dankook University,Cheonan,31116,Republic of Korea [7]UCL Eastman-Korea Dental Medicine Innovation Centre,Dankook University,Cheonan,31116,Republic of Korea

出　　处：《Bioactive Materials》2021年第1期123-136,共14页生物活性材料（英文）

基　　金：a National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT(2019R1C1C1002490,2018R1A2B3003446);by the Global Research Development Center Program(2018K1A4A3A01064257);by the Priority Research Center Program provided by the Ministry of Education(2019R1A6A1A11034536)。

摘　　要：Therapeutic options are quite limited in clinics for the successful repair of infected/degenerated tissues.Although the prevalent treatment is the complete removal of the whole infected tissue,this leads to a loss of tissue function and serious complications.Herein the dental pulp infection,as one of the most common dental problems,was selected as a clinically relevant case to regenerate using a multifunctional nanotherapeutic approach.For this,a mesoporous bioactive glass nano-delivery system incorporating silicate,calcium,and copper as well as loading epidermal growth factor(EGF)was designed to provide antibacterial/pro-angiogenic and osteo/odontogenic multiple therapeutic effects.Amine-functionalized Cu-doped bioactive glass nanospheres(Cu-BGn)were prepared to be 50–60 nm in size,mesoporous,positive-charged and bone-bioactive.The Cu-BGn could release bioactive ions(copper,calcium and silicate ions)with therapeutically-effective doses.The Cu-BGn treatment to human umbilical vein endothelial cells(HUVEC)led to significant enhancement of the migration,tubule formation and expression of angiogenic gene(e.g.vascular endothelial growth factor,VEGF).Furthermore,the EGF-loaded Cu-BGn(EGF@Cu-BGn)showed pro-angiogenic effects with antibacterial activity against E.faecalis,a pathogen commonly involved in the pulp infection.Of note,under the co-culture condition of HUVEC with E.faecalis,the secretion of VEGF was up-regulated.In addition,the osteo/odontogenic stimulation of the EGF@Cu-BGn was evidenced with human dental pulp stem cells.The local administration of the EGF@Cu-BGn in a rat molar tooth defect infected with E.faecalis revealed significant in vivo regenerative capacity,highlighting the nanotherapeutic uses of the multifunctional nanoparticles for regenerating infected/damaged hard tissues.

关 键 词：Nanotherapeutics Mesoporous bioglass nanospheres Copper ion/Growth factor Antibacterial/angiogenesis Osteogenesis/odontogenesis 

分 类 号：R318[医药卫生—生物医学工程]