Mechanisms of Brain Tissue Response to Implanted Devices

AA 第 I 部分（第 1 至 6、9 页） PI：MERRILL、DANIEL R 理事会：10/2002 卫生与人类服务部，1 F32 NS045454-01 Puuio.eamser_i：eA O D _ __'}Ntt_ 个人国家研究_l_'_'_"J_Vi_ I 双：PJ 0 ? S 2 6 IRG: ZRG1 F01(20) L 收到日期：04/05/2002 / ...................... Is',,, r_[nctton_ indic,sled on sample. I 会议日期 l 收到日期 1. 研究培训提案的标题（不要超过 58 个字符，包括空格和标点符号。） 大脑机制。组织对Im.pl.anted Devices Z. 级别奖学金 3. 博士后申请申请公告 4a. 申请人姓名（姓氏、名字、中间名首字母）Merrill, Daniel R. 4d，当前邮寄地址（街道、城市、州、邮政编码）2413 Woodmere Drive Cleveland Heights, OH 44106 4f. 办公室电话号码（区号、4g. 家庭电话号码和分机号）（区号和号码） (216_ 368-2378 (216_ 932,7202 美国公民或美国非公民国民或 5. 根据拟议奖励进行培训Lexicon) Disciplin?/_J_ _mCoatmegeoarym_am_ Engineering Form n NO I I YES（如果“是，请参阅第 5 页第 24 项） 7a. 拟授予奖项的日期 7b. 拟授予奖项的持续时间 8. 拟授予学位期间寻求的学位从 (MMIDD/YY) 到 (MM/DD/YY) (in预计完成 Dote 4b. 永久邮寄地址 31925 SE 40th Street Fall City, WA 98024 永久电话号码 4i. (425_222-4720)学位 B.S.、M.Eng.、PhE（街道、城市、州、邮政编码） 传真号码（区域 c_de 和号码）(216] 368-4R72 "_ 美国永久居民 6. 之前和/或当前 NRSA 支持（个人或机构） 9. 人类 9a. 如果“是”，豁免编号 9b。 保证主题 _oz 合规性 r-_ 否 IRB 批准日期 _ 全面审核或加急 r-_ 审核 1la。 赞助商姓名（姓氏、名字、中间名首字母） Tresco, Patrick, A。 电话 传真 (801) 581-8873 电子邮件地址_ (801) 585-5151 patrick, fresco@utah, edu 11c. 服务、实验室或同等部门 工程学院 131 如果与第 1la 项不同，请注明将进行研究培训的机构的名称和地址。 ross 10. 动物脊椎动物 10e. 如果=是，" 编号 IACUC 批准 10b. 动物福利 r_NO 日期保证编号 RYES !0/06/01 A3031-0] 1lb. 拟议赞助机构名称 Addr_&versity of Utah 1471 Federal Way Salt Lake City, UT 84102 12. 实体识别号 876000525 DUNSNO._ava_b_ 00909-5565 14. 官方名称 Vincent Bogdanski，赠款官员 电话 (801) 581-3008 传真 (801) 581-3007 职务 地址 赞助项目办公室1471 Federal Way Salt Lake City, UT 84102 电子邮件 _dress v.b0g_danski@osp.utah.edu 15. 申请人证明和接受：我保证，据我所知，本文中的陈述是真实、完整和准确的，并且我同意遵守公共卫生服务条款和条件（如果因本申请而颁发奖项），我知道任何虚假、不实信息。虚构或欺诈性的陈述或主张可能会使我受到刑事、民事或行政处罚。我证明我已阅读国家研究服务奖 8 诱惑保证，如果做出奖励，我将遵守该保证，并且该奖项不会支持 PHS 416-1（修订版 12/98）FACE PAGE AA。 _t_l-'Ail-It(/-orm I_a9o$ 7 tO b; ,YJ 个人 NRSA 申请 Merrill, Daniel R. 姓名（姓氏、名字、中间名首字母） I6 APP(TuocbAe .cTomSEplOeteUd CbyAaTpp*l/Ocan.t--遵循 PHS 416-1 说明) DER, EEl 年现场机构导师B.S. [ 1983 年 5 月 康梅尔大学 电气工程硕士 I 5 月 [ 1984 年 康梅尔大学 电气工程 Joseph Rosson Case Westem Reserve University J.Thomas Mortimer 2002 生物医学工程 17. 申请人培训/就业 (Aflercollege) 活动/开始结束职业日期 (mmlyy) 日期 {rnrrdyy)现场机构/公司主管工程师 07/84 05/86 霍尼韦尔公司电气工程 Richard Knapp 水下声学负责人 05/86 07/95 Quinton 仪器公司电气工程 Alex Bellamy 生物医学仪器工程师 18. GQALSFOR.FELLOWSHI.TpRAININGANDCAIEER 打算继续研究。 6. 恢复神经系统退化功能的工程方法。我现在希望将重点转向神经组织的界面和控制或再生的组织工程方法，包括其电化学影响，以及神经系统修复的细胞和组织工程方法，我希望在我的学术研究生涯中跨越这些领域。技能，包括细胞培养和组织学方法；因此，我希望与能够指导这些实验技能的研究人员合作，同时受益于我的背景，这里提出的项目很好地解决了我想要的实验培训，包括细胞培养、动物手术、电生理记录、固定和组织处理、免疫组织化学技术以及其他支持性实验室技术，在本培训期结束时，我将拥有一套非常强大和有用的技能，可以用于研究生物材料与神经系统的相互作用。 19. 姓名和学位 20. 职位]排名 21. 研究兴趣/领域 22. 描述（不要超过 SP( )NSOR Patrick A. Tresco_ 博士副教授..... 提供生物材料、伤口愈合机制和组织工程空间）(]) 将研究长期植入生物医学设备性能下降的机制。将进行电生理学记录以测量电极阻抗并记录植入后 3 至 28 天的动物，并应用免疫组织化学方法评估电阻抗和记录活性的变化与组织反应的关系。 (2) 在基线表征后，将在体外对微电极的阻抗进行表征，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），并且将在不同时间固定培养物并使用间接免疫组织化学和细胞类型特异性标记物进行检查。 (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 3-D 培养模型，并使用显微镜方法和间接免疫组织化学评估反应。该项目的长期目标是制定方法并更好地了解伤口。 PHS 416-1（修订版 12198）表格第 2 页 BB cc 姓名（姓氏、名字、中间名首字母） 个人 NRSA 应用目录 ====================================================================================

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 drm2@po.cwru.edu 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 (801) 581-8873 E-mail Addres_ (801) 585-5151 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 (801) 581-3008 Fax (801) 581-3007 Title Address Office of Sponsored Projects 1471 Federal Way Salt Lake City, UT 84102 E-mail _dress v.b0g_danski@osp.utah.edu 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===========================================