Highly Elastic Biomaterial Development for Urethral Application

尿道应用的高弹性生物材料开发

基本信息

批准号：
10573094
负责人：
Renea Sturm
金额：
$ 17.04万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10573094
关键词：
Address Adipose tissue Adolescent Adult Advisory Committees Affect Anatomy Animals Anterior Autologous Award Biocompatible Materials Biological Biomechanics Biomedical Engineering Biomimetics Birth California Categories Cell Adhesion Cell Line Cells Cellular biology Characteristics Cheek structure Child Childhood Chronic Collagen Communication Defect Deposition Development Diagnosis Disease Diverticulum Doctor of Philosophy Educational workshop Elasticity Elastin Engineering Evaluation Expenditure Extracellular Matrix Fistula Future Gelatin Goals Human Hydrogels Hypospadias In Vitro Infection Insurance Carriers Knowledge Leadership Learning Libraries Life Los Angeles Lower urinary tract Malignant - descriptor Malignant Neoplasms Mechanics Mentors Mentorship Mesenchymal Stem Cells Methacrylates Methodology Methods Modeling Modulus Morbidity - disease rate Morphology Nanotopography Natural regeneration Operative Surgical Procedures Oryctolagus cuniculus Outcome Patients Penile Erection Peptides Phenotype Physicians Polymers Postoperative Complications Privatization Procedures Property Reconstructive Surgical Procedures Reproducibility Research Research Design Research Personnel Role Scientist Secondary to Site Skin Smooth Muscle Source Structure Surgeon Techniques Tensile Strength Testing Tissue Engineering Tissue constructs Tissues Training Trauma Tube Tubular formation Universities Urethra Urethral Stricture Urinary tract Urologic Surgeon Urology Urothelium Vascularization Work biomaterial development boys care costs career cell behavior clinical translation cohort congenital anomaly cost design fabrication high risk immunoregulation implantation improved in vivo male materials science mechanical properties men novel penis foreskin polycaprolactone prepuberty professor repaired replacement tissue scaffold skills standard of care stem cells symposium tissue regeneration tissue repair translational goal wound healing wound vascularization

项目摘要

PROJECT SUMMARY This is an initial submission of a K08 application by Dr. Renea Sturm, an Assistant Professor of Pediatric Urology at the University of California, Los Angeles (UCLA). Candidate: Dr. Sturm’s primary training objectives in this proposal are to: 1. Fill existing knowledge gaps in the interaction between materials science and modeling 2. Learn scientific methodologies in material fabrication and evaluation 3. Develop study design and scientific communication skills 4. Develop management and leadership skills for a career as an independent investigator. Dr. Sturm will accomplish these activities through mentorship, focused coursework, and participation in select workshops/conferences. This will be supported by her primary mentors Song Li, PhD, Chair of Bioengineering at UCLA and an expert in cellular-materials interactions and co-mentor Nasim Annabi, PhD, an expert in modifiable elastic hydrogels. She will be further supported by mentor Isla Garraway, MD, PhD, an independent urologic surgeon-scientist. Her external advisory committee will include focused materials science and tissue engineering expertise through Ali Khademhosseini, PhD with expert knowledge of tissue engineering for the lower urinary tract provided by Arun Sharma, PhD. Research: Urethral defects requiring urethroplasty occur in children and adults secondary to congenital, traumatic, infectious, and malignant conditions. Current tissue sources for urethral replacement are limited by donor site morbidity and lack of optimal tissue characteristics to support lifelong voiding and penile erections. A subsequent high risk of short- and long-term urethroplasty complications highlights the need for an improved tissue alternative with a bioinspired design. The goal of this proposal is to establish an independent surgeon- scientist with focused materials expertise and a track record of creating and evaluating a highly elastic, biomimetic urethral scaffold with optimized biomechanical properties by layer to support cellularization followed by extracellular matrix (ECM) deposition. The research plan addresses key design requirements: 1) optimized mechanical properties, 2) reproducible synthesis methods, and 3) wound healing and vascularization. Our overall hypothesis is that a novel scaffold with the proposed combination of a hydrogel and elastin-like peptide designed to meet targeted mechanical and structural parameters will improve suturability, early urinary tract function, and local tissue recapitulation as compared to preputial or unseeded scaffold urethroplasties. In Aim 1, composite electrospun scaffolds will be engineered with mechanical and structural properties that mimic native urethral tissue. In Aim 2, an in vitro evaluation will elucidate the role of the mechanical niche in cellular behavior and ECM deposition. In Aim 3, an ex vivo evaluation of functional and anatomic findings following application of seeded and unseeded grafts will occur versus standard of care preputial urethroplasty. Put together, this research strategy will engineer finely tuned elastic biomimetic scaffolds with target mechanical and structural parameters derived from urethral tissue analyses to maximize future clinical translatability.

项目概要这是小儿泌尿科助理教授 Renea Sturm 博士首次提交的 K08 申请在加州大学洛杉矶分校（UCLA）。候选人：Sturm 博士在本提案中的主要培训目标是： 1. 填补以下方面的现有知识空白：材料科学与建模之间的相互作用 2. 学习材料制造中的科学方法和评估 3. 培养研究设计和科学沟通技巧 4. 培养管理和能力 Sturm 博士将通过独立调查员的职业生涯的领导技能来完成这些活动。指导、重点课程以及参加选定的研讨会/会议将得到支持。她的主要导师李松博士，加州大学洛杉矶分校生物工程系主任，细胞材料专家互动和共同导师纳西姆·阿纳比博士是可修改弹性水凝胶的专家，她将进一步研究。我得到了独立泌尿外科医生兼外部顾问 La Garraway 博士的支持。委员会将包括 Ali Khademhosseini 的重点材料科学和组织工程专业知识，由 Arun Sharma 博士提供的具有下尿路组织工程专业知识的博士学位。研究：需要尿道成形术的尿道缺陷发生在儿童和成人中，继发于先天性、目前用于尿道置换的组织来源受到以下因素的限制。供体部位发病率和缺乏支持终生排尿和阴茎勃起的最佳组织特征。随后发生短期和长期尿道成形术并发症的高风险凸显了改进尿道成形术的必要性该提案的目标是建立一个独立的外科医生-具有仿生设计的组织替代品。科学家拥有专注的材料专业知识以及创建和评估高弹性、仿生尿道支架具有逐层优化的生物力学特性以支持细胞化随后是细胞外基质 (ECM) 沉积。该研究计划解决了关键设计要求：1) 优化的机械性能，2）可重复的合成方法，3）伤口愈合和血管化。我们的总体假设是，一种新型支架具有所提出的水凝胶和类弹性蛋白的组合旨在满足目标机械和结构参数的肽将提高可缝合性、早期尿与包皮或未种植支架尿道成形术相比，尿道功能和局部组织再现。在目标 1 中，复合电纺支架将被设计为具有机械和结构特性，在目标 2 中，体外评估将阐明机械生态位的作用。目标 3 中的细胞行为和 ECM 沉积，功能和解剖学发现的离体评估。与标准护理包皮尿道成形术相比，应用播种和未播种移植物后将发生。总而言之，该研究策略将设计具有目标机械性能的精细调整的弹性仿生支架和来自尿道组织分析的结构参数，以最大限度地提高未来的临床可转化性。