Mechanisms of Brain Tissue Response to Implanted Devices

脑组织对植入装置的反应机制

• 批准号: 6836467
• 负责人: DANIEL R MERRILL
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836467
• 关键词: Mechanisms; Brain; Tissue; Response; Implanted

AA PART I(Forrn Pages 1 to6, 9) PI: MERRILL, DANIEL R Council: 10/2002 Department of Health andHuman Services , 1 F32 NS045454-01 Puuio.eamser_i:eA O D _ __'}Ntt_ Individual National Resear_l_'_'_"J_Vi_ I Dual: PJ 0 ? S 2 6 IRG: ZRG1 F01(20) L Received:04/05/2002 / .................. Is',,, r_[nctton_ indic,sled on sample. I Meeting Dates l Date Received 1. TITLE OF RESEARCH TRAINING PROPOSAL (Do not exceed 58 characters, including spaces and punctuation.) Mechanisms of Brain .Tissue Response to Im.pl.anted Devices Z. LEVELOF FELLOWSHIP . 3. PROGRAM ANNOUNCEMENTfREQUEST FOR APPLICATIONS Postdoctoral 4a. NAME OF APPLICANT (Last, first, middle initial) Merrill, Daniel R. 4d, PRESENT MAILING ADDRESS (Street, city, state, zip cede) 2413 Woodmere Drive Cleveland Heights, OH 44106 4f. OFFICE TELEPHONE NO. (Area code, 4g. HOME TELEPHONE NO. no., and ext.) (Area code and no.) (216_ 368-2378 (216_ 932,7202 U,S. CITIZEN OR U.S. NONCITIZEN NATIONAL or 5. TRAINING UNDER PROPOSED AWARD (See Lexicon) Disciplin?/_J_ _mCoatmegeoarym_am_ Engineering Form n NO I I YES (If"Yes, refer to Item 24, Page 5) 7a. DATES OF PROPOSED AWARD 7b. PROPOSED AWARD DURATION 8. DEGREE SOUGHT DURING PROPOSED AWARD From (MMIDD/YY) .Through (MM/DD/YY) (in month_) Degtee Expected Completion Dote 4b. E-MAIL [e-mail] 4e. PERMANENT MAILING ADDRESS 31925 SE 40th Street Fall City, WA 98024 4h. PERMANENT PHONE NO. 4i. (Area code and no.) (425_222-4720 4c. HIGHEST DEGREE(S) B.S., M.Eng., PhE (Street, city, state, zip code) FAX NUMBER (Area c_de and no.) (216] 368-4R72 "_ PERMANENT RESIDENT OF U.S. 6. PRIOR AN D/OR CURRENT NRSA SUPPORT (Jndfvidual or Institutional) 9. HUMAN 9a. If "Yes," Exemption No. 9b. Assurance SUBJECTS _oz Compliance r-_ No IRB Approval Date _ FulllRB or Expedited r-_ YEs Review 1la. NAME OF SPONSOR (Last, first, middle initial) Tresco, Patrick, A. Telephone Fax [phone] E-mail Addres_ [phone] patrick, fresco@utah, edu 11c. DEPARTMENT, SERVICE, LABORATORY, OR EQUIVALENT Department of Bioengineering 11d. MAJOR SUBDIVISION College of Engineering 131 NAME AN D TE LEPHON E NO. OF ADVISOR IF DtFFERENT FROM 1la. Telephone Name and address of institution where research training will take place if different from Item 1lb. Add ross 10. VERTEBRATE of ANIMALS 10e. If=Yes," No. IACUC approval 10b. Animal Welfare r_NO date Assurance No. RYES !0/06/01 A3031-0] 1lb. NAME OF PROPOSED SPONSORING INSTITUTION Addr_&iversity of Utah 1471 Federal Way Salt Lake City, UT 84102 12. ENTITY IDENTIFICATION NO. 876000525 DUNSNO._ava_b_ 00909-5565 14. NAMEOFOFFICIALINBUSINESSOFFICE Vincent Bogdanski, grants officer Telephone [phone] Fax [phone] Title Address Office of Sponsored Projects 1471 Federal Way Salt Lake City, UT 84102 E-mail _dress [e-mail] 15. APPLICANT CERTIFICATION AND ACCEPTANCE: I certify that the statements herein are true, complete, and accurate to the best of my knowledge, and I agree to comply with the Public Health Service terms anc_ conditions if an award is issued as a result of this application. I am aware that any false, fictitious, or fraudulent statements or claims may subject me to criminal, civil, or administrative penalties. I certify that I have read the National Research Servioe ,award 8entice Assurance, that I will abide by the Assurance if an award is made, and that the award will not support residency training. PHS 416-1 (Rev. 12/98) FACE PAGE AA _t_l-'Ail-It(/-orm I_a9o$ 7 tO b; ,YJ Individual NRSA Application Merrill, Daniel R. NAME (Last, first, middle initial) I6 APP(TuocbAe .cTomSEplOeteUd CbyAaTpp*l/Ocan.t--follow PHS 416-1 instructions) DER, EEl YEAR FIELD INSTITUTION MENTOR B.S. [ May [ 1983 Electrical Engineering Comell University M.Eng. I May [ 1984 Electrical Engineering Comell University Joseph Rosson Case Westem Reserve University J.Thomas Mortimer 2002 Biomedical Engineering 17. APPLICANTS TRAINING/EMPLOYMENT (Aflercollege) ACTIVITY/ BEGINNING ENDING OCCUPATION DATE (mmlyy) DATE {rnrrdyy) FIELD INSTITUTION/COMPANY SUPERVISOPdEMPLOYER Engineer 07/84 05/86 Electrical Engineering, Honeywell, Inc. Richard Knapp Underwater Acoustics Principal 05/86 07/95 Electrical Engineering, Quinton Instrument Co. Alex Bellamy Engineer Biomedical Instrumentation 18. GQALSFOR.FELLOWSHI.TpRAININGANDCAEIEER. . intend to continue research m the 6arectmn ot engineering approaches to restoring degraded function in the nervous system. My doctoral training has involved electrochemical processes occurring on stimulating electrodes. I now desire to shift my focus to tissue engineering approaches to interface and control or regeneration of nervous tissue. I believe there is substantial unexploited overlap in the fields of functional electrical stimulation of excitable tissue, including its electrochemical implications, and cellular and tissue enginzering approaches to nervous system repair. I wish to span these areas in my academic research career. My experimental weakness is in tissue engineering laboratory skills, including cell culturing and histological methods; thus I desire to collaborate with investigators who can mentor such experimental skills while benefiting from my background. The project proposed here addresses well my desired experimental training, and involves ceil culturing, animal surgery, electrophysiological recording, fixation and tissue handling, immunohistochemieal technique, and other supporting laboratory techniques. At the end of this training period I will possess a very robust and useful set of skills for which to study biomaterial interaction with the nervous system as applied to numerous approaches for repair. 19. NAME AND DEGREE(S) 20. POSITION]RANK 21. RESEARCH INTERESTS/AREAS 22. DESCRIPTION (Do not exceed SP( )NSOR Patrick A. Tresco_ PhD Associate Profe ..... Biomaterials, Mechanisms of wound healing & Tissue Eng. space provided) (]) The mechanisms underlying decreased performance of chronically implanted biomedical devices will be investigated. Microelectrode arrays will be implanted into the auditory cortex of adult rats. Electrophysiological recordings will be performed to measure electrode impedance and record evoked single u_nit activity. Animals will be sacrificed from 3 to 28 days post-implant and immunohistochemical methods applied. The adsorbed cell t3.qgeson retrieved microelectrodes will be evaluated. Changes in electrical impedance and recording activity will be correlated with tissue response. The objective is to determine how microglial ceils and astrocytic components contribute to increasing electrical impedance and loss of single unit recording with recording electrodes. (2) The impedance of microelectrodes will be characterized in vitro based on adsorbing species availability. After baseline characterization, i extracellular molecules will be added to the media including proteins and ceils (reactive microglia, astrocytes, and! fibroblasts) and characterization will continue. Cultures will be fixed at various times and examined using indirect immunohistochemistry and cell type specific markers. Changes in impedance will be correlated with adsorbing species and the extent of cell colonization. (3) A resting 3-D culture model of cortical brain tissue will be created using mixed primary ceils suspended in an extracellular matrix gel. Serum treated probes will be implanted, and the response evaluated using microscopic methods and indirect immunohistochemistry. The ability to detect sequential ;changes in rnicroglial activation will be evaluated. The long-term objective of this project is to formulate approaches ¿ r v _a" i nalitv and to better understand the wound healin_onse in brain. PHS 416-1 (Rev. 12198) Form Page 2 BB cc NAME (Last, first, middle initial) Individual NRSA Application Table of Contents ========================================Section End===========================================

a PART I(forth page 1 to 6,9) PI: MERRILL, DANIEL R Council: 10/2002 Department of Health andHuman Services, 1 F32 NS045454-01 Puuio。eamser_i: eA O D _ __“}Ntt_个别国家Resear_l_”_“_”J_Vi_我双:PJ 0 ?年代2 6尾声:ZRG1 F01 (20) L收到:04/05/2002 / ..................是“…r_[ntton_索引，雪橇上的样品。”1会议日期1收到日期研究培训计划的标题（不超过58个字符，包括空格和标点符号）大脑的机制。组织对植入器械的反应。3. 项目公告：申请频率博士后4a。申请人姓名（最后，第一，中间首字母缩写）Merrill, Daniel R. 4d，目前通讯地址（街道，城市，州，邮编）2413 Woodmere Drive Cleveland Heights, OH 44106 4f。办公室电话号码。(区号是4g。家庭电话号码。不。)（区号和电话号码）[216_368 -2378] [216_932,7202]；美国公民或非美国公民国民或5。拟议奖励下的培训（见词典）纪律？1 .如果“是”，请参考第5页第24项。建议赔偿的日期7b。建议奖励期限8。在计划授予期间获得学位（中/YY）。通过（MM/DD/YY）（以月为单位_）度预期完成度电子邮件[e-mail] 4e。永久通讯地址31925东南40街福尔城，华盛顿州98024小时。固定电话号码。4我。（区号和电话号码）(425 _222 - 4720 4 c。最高学位(S)理学士，硕士。， PhE（街道，城市，州，邮政编码）传真号码（地区c_de和号码）[216]美国永久居民。以前和/或目前的NRSA支持（个人或机构）人类的9。如“是”，第9b号豁免。保证对象_合规r-_无IRB批准日期_完全或加急r-_是审核1la。发起人姓名（尾、首、中首字母缩写）Tresco, Patrick， A.电话传真[phone]电子邮件地址_ [phone] Patrick, fresco@utah, edu 11c。生物工程系，服务部，实验室，或同等部门专业分部工程学院131校名及校号。顾问的不同之处。如果与第1lb项不同，研究培训机构的名称和地址。加上罗斯10。动物中的脊椎动物如果=是的,“没有。IACUC批准10b。动物福利r_NO日期保证编号裸麦大量![06/06/01] 1磅。提议的赞助机构名称：犹他大学1471联邦路盐湖城，UT 84102实体识别号876000525 DUNSNO。[au:] [au:]Vincent Bogdanski，资助官员电话[phone]传真[phone]标题地址资助项目办公室1471联邦路盐湖城，UT 84102 E-mail _dress [e-mail]申请人证明和接受：我保证在此陈述的内容是真实、完整和准确的，并且我同意遵守公共卫生服务的条款和条件，如果这个申请的结果是颁发奖励。我知道任何虚假、虚构或欺诈性的陈述或索赔可能使我受到刑事、民事或行政处罚。我保证我已经阅读了国家研究服务，奖励8诱使保证，如果有奖励，我将遵守保证，并且该奖励不会支持住院医师培训。PHS 416-1 (Rev. 12/98) FACE PAGE AA _t_l-'Ail-It(/-orm i_a90 $ 7 tO b;,YJ Individual NRSA Application Merrill, Daniel R. NAME（尾，首，中首字母）I6 APP（TuocbAe .）cTomSEplOeteUd CbyAaTpp * l / Ocan。（按PHS 416-1指示）DER， EEl YEAR FIELD INSTITUTION MENTOR理学士[1983年5月]Comell University电气工程硕士[5] 1984电气工程科梅尔大学Joseph Rosson Case西储大学J.Thomas Mortimer 2002生物医学工程应聘者培训/就业（毕业后）活动/开始/结束职业日期（月）日期（月）实习机构/公司主管雇主工程师84 / 07/ 86 / 05，霍尼韦尔公司电气工程Richard Knapp水下声学主管2005年5月至1995年7月昆顿仪器公司电气工程Alex Bellamy工程师生物医学仪器GQALSFOR.FELLOWSHI.TpRAININGANDCAEIEER。。打算继续研究6个领域的工程方法来恢复神经系统退化的功能。我的博士训练涉及在刺激电极上发生的电化学过程。我现在希望把我的重点转移到组织工程方法的接口和控制或再生的神经组织。我相信，在可兴奋组织的功能性电刺激领域，包括其电化学意义，以及神经系统修复的细胞和组织工程方法，存在大量未开发的重叠。我希望在我的学术研究生涯中跨越这些领域。我的实验劣势是组织工程实验技能，包括细胞培养和组织学方法；因此，我希望与研究人员合作，他们可以指导这些实验技能，同时受益于我的背景。这里提出的项目很好地满足了我想要的实验训练，包括细胞培养、动物外科、电生理记录、固定和组织处理、免疫组织化学技术和其他配套的实验室技术。在这个培训期结束时，我将拥有一套非常强大和有用的技能，用于研究生物材料与神经系统的相互作用，并将其应用于多种修复方法。19. 姓名和学位位置)排名21。研究兴趣/领域描述(不超过SP()NSOR Patrick A. Tresco_ PhD Associate Profe .....生物材料，伤口愈合机制与组织工程。（]）长期植入的生物医学设备性能下降的机制将被研究。微电极阵列将被植入成年大鼠的听觉皮层。电生理记录将用于测量电极阻抗并记录诱发的单个u_nit活动。动物在植入后3 ~ 28天处死，采用免疫组织化学方法。被吸附的细胞t3。Qgeson检索微电极将被评估。电阻抗和记录活动的变化将与组织反应相关。目的是确定小胶质细胞和星形胶质细胞成分如何增加电阻抗和记录电极单单元记录的损失。(2)微电极的阻抗将基于吸附物质的有效性进行体外表征。基线鉴定后，将细胞外分子添加到包括蛋白质和细胞(反应性小胶质细胞、星形胶质细胞和！成纤维细胞)和表征将继续进行。培养物将在不同时间固定，并使用间接免疫组织化学和细胞类型特异性标记进行检查。阻抗的变化将与吸附种类和细胞定植的程度有关。(3)将使用悬浮在细胞外基质凝胶中的混合原代细胞创建静息的大脑皮质组织三维培养模型。经血清处理的探针将被植入，并使用显微镜方法和间接免疫组织化学评估反应。检测顺序的能力；将评估神经胶质细胞活化的变化。该项目的长期目标是制定治疗“伤口愈合”的方法，并更好地了解伤口愈合在大脑中的作用。小灵通416 - 1(12198年启)表单页面2 BB cc的名字(最后,首先,初始)个人NRSA应用程序目录 ======================================== 节结束 ===========================================