Ultrasoft and Highly Stretchable Hydrogel Optical Fibers for In Vivo Optogenetic.docx

and the elucidation of neuropsychiatric disease mechanisms.i12j Recent optogenetics developments have provided a potential treatment of epiIepsy,(3,4 Par- kinson,s disease,s,6 depression"网 and other brain disorders,(9- nj where the cell type-specific modulation of neural circuits may address the pathological symptoms.i21 To manipulate the activities of specific neurons or neural circuits in vivo using optogenetics, implantable optical waveguides are frequently used to deliver laser light into the virus-infected brain regions.”/ Primarily, these waveguides are silica optical fibers, with an average Young,s modulus at least six orders of magnitudes larger than that of the neural tissues415-17 The elastic mismatch between the silica optical fibers and organisms may lead to the host tissue injuries, which subsequently induce neuronal death in the implant surroundings. To prevent this, stretchable and flexible optoelectronic implantss- 21 and polymer integrated PrObeS【22- 25j have been developed, with a decreased tissue response and consistent performance duringCOMMUNICATIONwww.advopticalmat.deHydrogelOpticalFibersUltrasoftandHighlyStretchableHydrogelOpticalFibersforInVivoOptogeneticModulations1.uluWang,ChengZhong,DingningKe,FengmingYefJieTu,LipingWang/andYiLu*Optogeneticshasbeenwidelyappliedasacell-specifictechniquewithhightemporalresolutionforthemodulationofneuralcircuitryinvivo,offeringpotentialnoveltreatmentsforneuropsychiatricdiseases.However,todate,themostwidelyusedoptogeneticswaveguidesremainsilicaopticalfibers,whichmayleadtoamismatchinthemechanicalpropertiesbetweentheimplantsandneuraltissues.Toresolvethisissue,alginate-polyacrylamidehydrogelopticalfiberscanbefabricatedinasimplifiedone-stepprocess,andtheyshowsignificantlyimprovedcharacteristicsfortheinvivoOptogeneticapplications,includinglowlight-propagationlossandYoung,smodulus,andhighstretchability.AftertheexpressionofAAV-CaMKII<-ChR2-mCherryfbluelightpulsesaredeliveredintohippocampususingahydrogel-optrodearray,andfrequency-dependentneuralresponsescanbeobserved.Moreover,Optogeneticstimulationthroughthechronicimplantedhydrogelopticalfibersintheprimarymotorcortexcanconsiderablymodulatetheanimasbehavior.Hydrogel fibers significantly alleviate tissue response at the implant/neuralinterface, compared with that observed using the silica optical fibers. Takentogether, the results of this study demonstrate the feasibility and advantagesof the hydrogel optical fiber use for chronic Optogenetic modulation in free-moving animals. Hydrogel implant use may allow the development of noveltherapeutic strategies for the treatment of neuropsychiatric disorders.Optogeneticsallowsapreciselytimedcontrolofspecificneuronsubtypesinfree-behavinganimals,whichhasbeenwidelyappliedforthedeterminationofneuralcircuitcharacteristics1.WangfDr.C.Zhong,F.Ye,Prof.J.Tu,Prof.L.WanglDr.Y.LuCollaborativeInnovationCenterforBrainScienceCASCenterforExcellenceinBrainScienceandIntelligenceTechnologyTheBrainCognitionandBrainDiseaseInstituteShenzhenInstitutesofAdvancedTechnologyChineseAcademyofSciencesShenzhen518055,ChinaE-mail:lp.wang;luyi1.Wang,F.YeShenzhenCollegeofAdvancedTechnologyUniversityofChineseAcademyofSciencesShenzhen518055,ChinaDr.D.KeExperimentandInnovationCenterHarbinInstituteofTechnologyShenzhenGraduateSchoolShenzhen518055,ChinaTheORCIDidentificationnumber(s)fortheauthor(s)ofthisarticlecanbefoundunderhttps:/d0i.0rg/l0.1002adom.201800427.DOI:10.1002adom.201800427chronicimplantations.However,thecomplexandexpensivefabricationprocessoftheimplantableoptoelectronicsandtherelativelylowdeformabilityofthepolymerintegratedprobesmayhindertheirWidaiP-dOpplicatihng.Moncoginhydrogel-basedopticalfiberprovidealowpropagationlosswaveguidewithmuchhigherstretchabilityandlowerYoung,smodulus,%2whichmaylargelyeliminatetheeffectsofthemechanicalmismatchandtissuemovements.115,29However,thefeasibilityandadvantagesofthehydrogelopticalfiberuseforchronicOptogeneticbrainmodulationinfree-movinganimalshavenotbeensystematicallyinvestigated.Adv.OpticalMater.2018,6,18004271800427Here,wedevelopedasimplifiedmethodforthe>igqpdatoflow-modulusandhigh-stretchablealgi1eQ(amideSi(PAAm)hydrogelopticalfibersandinvestigc3T15(pplica-tioninvivo.ThoOlGinat。PAAmprecursor?andcross-linkedinasimplifiedone-stepprocess,whileits三molecularstructurewasconfirmedusingtheRamanspectraganalysis(Figure1a).WiththeincreaseinthePAAmcontents,mainbandintensityincreasedaswell:1101cm1attheNH2itwisting,1322cm1attheCH2wagging,1429cm1atthe.CNvibration,1452cm1attheCH2bending,1621cm1JattheCOstretchingvibration,and1677cm1attheNH(1of6)©2018WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim(SeCQheTermsandcondn(https<o3三,2.-brlryw=cyortcnsMndcond-tns)03W=Cyo35oL-bruryforruns。-USeo>Figure 1. Chemical an