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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.

项目总结