Regulating the proinflammatory response to composite biomaterials by targeting immunometabolism  

作　　者：Chima V.Maduka Ashley V.Makela Anthony Tundo Evran Ural Katlin B.Stivers Maxwell M.Kuhnert Mohammed Alhaj Ehsanul Hoque Apu Nureddin Ashammakhi Kurt D.Hankenson Ramani Narayan Jennifer H.Elisseeff Christopher H.Contag 

机构地区：[1]Comparative Medicine&Integrative Biology,Michigan State University,East Lansing,MI,48824,USA [2]Department of Biomedical Engineering,College of Engineering,Michigan State University,East Lansing,MI,48824,USA [3]Institute for Quantitative Health Science&Engineering,Michigan State University,East Lansing,MI,48824,USA [4]Translational Tissue Engineering Center,Johns Hopkins University School of Medicine,Baltimore,MD,21231,USA [5]Department of Chemical Engineering&Materials Science,Michigan State University,East Lansing,MI,48824,USA [6]Department of Biomedical Sciences,College of Dental Medicine,Lincoln Memorial University,Knoxville,TN,37917,USA [7]Department of Orthopedic Surgery,University of Michigan Medical School,Ann Arbor,MI,48109,USA [8]Department of Biomedical Engineering,Johns Hopkins University School of Medicine,Baltimore,MD,21231,USA [9]Department of Microbiology,Genetics&Immunology,Michigan State University,East Lansing,MI,48864,USA [10]BioFrontiers Institute,University of Colorado,Boulder,CO 80303,USA.

出　　处：《Bioactive Materials》2024年第10期64-73,共10页生物活性材料（英文）

基　　金：Funding for this work was provided in part by the James and Kathleen Cornelius Endowment at MSU.The Mass Spectrometry core at MSU,especially A.J.Schilmiller and J.O’Keefe,helped to analyze releasates.

摘　　要：Composite biomaterials comprising polylactide(PLA)and hydroxyapatite(HA)are applied in bone,cartilage and dental regenerative medicine,where HA confers osteoconductive properties.However,after surgical implantation,adverse immune responses to these composites can occur,which have been attributed to size and morphology of HA particles.Approaches to effectively modulate these adverse immune responses have not been described.PLA degradation products have been shown to alter immune cell metabolism(immunometabolism),which drives the inflammatory response.Accordingly,to modulate the inflammatory response to composite biomaterials,inhibitors were incorporated into composites comprised of amorphous PLA(aPLA)and HA(aPLA+HA)to regulate glycolytic flux.Inhibition at specific steps in glycolysis reduced proinflammatory(CD86+CD206-)and increased pro-regenerative(CD206+)immune cell populations around implanted aPLA+HA.Notably,neutrophil and dendritic cell(DC)numbers along with proinflammatory monocyte and macrophage populations were decreased,and Arginase 1 expression among DCs was increased.Targeting immunometabolism to control the proinflammatory response to biomaterial composites,thereby creating a pro-regenerative microenvironment,is a significant advance in tissue engineering where immunomodulation enhances osseointegration and angiogenesis,which could lead to improved bone regeneration.

关 键 词：HYDROXYAPATITE POLYLACTIDE Immunometabolism INFLAMMATION Regenerative medicine 

分 类 号：TB33[一般工业技术—材料科学与工程]