Developing a SMART scaffold for bladder augmentation

开发用于膀胱扩张的 SMART 支架

• 批准号: 10429930
• 负责人: Guillermo Antonio Ameer
• 金额: $ 68.14万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-09 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10429930
• 关键词: Acute Kidney Failure; Anatomy; Animal Model; Antioxidants; Autologous; Biocompatible Materials; Biologic Characteristic; Bladder; Bladder Control; Bladder Tissue; Blood Vessels; CD34 gene; Catheterization; Cells; Citrates; Clinical; Clinical Research; Data; Development; Disease; Elasticity; Elastomers; Electronics; Engineering; Extravasation; Failure; Functional Regeneration; Glycolates; Goals; Hematopoietic stem cells; Heterogeneity; Human; Inflammatory; Interstitial Cystitis; Intestines; Kidney Failure; Life; Light; Malignant - descriptor; Measures; Mesenchymal Stem Cells; Modeling; Monitor; Natural regeneration; Operative Surgical Procedures; Outcome; Papio; Pathologic; Patient Care; Patient-Focused Outcomes; Patients; Perforation; Performance; Phylogenetic Analysis; Physics; Physiological; Polymers; Predisposition; Problem Solving; Process; Radiation therapy; Rattus; Regenerative engineering; Reporting; Safety; Science; Scientist; Serious Adverse Event; Small Intestinal Submucosa; Spinal Dysraphism; Stretching; System; Technology; Telemetry; Time; Tissues; Trauma; United States; Urine; Urologic Cancer; Work; base; biocompatible scaffold; biomaterial compatibility; bone marrow mesenchymal stem cell; canine model; clinical translation; clinically relevant; design; experimental study; improved; in vivo; innovation; materials science; mechanical properties; optogenetics; outcome prediction; poly(lactic acid); pre-clinical; pressure; reconstruction; regeneration function; regenerative; scaffold; scale up; standard of care; stem cells; surgery outcome; tissue regeneration; tool; wireless electronic; wireless transmission; Acute Kidney Failure; Anatomy; Animal Model; Antioxidants; Autologous; Biocompatible Materials; Biologic Characteristic; Bladder; Bladder Control; Bladder Tissue; Blood Vessels; CD34 gene; Catheterization; Cells; Citrates; Clinical; Clinical Research; Data; Development; Disease; Elasticity; Elastomers; Electronics; Engineering; Extravasation; Failure; Functional Regeneration; Glycolates; Goals; Hematopoietic stem cells; Heterogeneity; Human; Inflammatory; Interstitial Cystitis; Intestines; Kidney Failure; Life; Light; Malignant - descriptor; Measures; Mesenchymal Stem Cells; Modeling; Monitor; Natural regeneration; Operative Surgical Procedures; Outcome; Papio; Pathologic; Patient Care; Patient-Focused Outcomes; Patients; Perforation; Performance; Phylogenetic Analysis; Physics; Physiological; Polymers; Predisposition; Problem Solving; Process; Radiation therapy; Rattus; Regenerative engineering; Reporting; Safety; Science; Scientist; Serious Adverse Event; Small Intestinal Submucosa; Spinal Dysraphism; Stretching; System; Technology; Telemetry; Time; Tissues; Trauma; United States; Urine; Urologic Cancer; Work; base; biocompatible scaffold; biomaterial compatibility; bone marrow mesenchymal stem cell; canine model; clinical translation; clinically relevant; design; experimental study; improved; in vivo; innovation; materials science; mechanical properties; optogenetics; outcome prediction; poly(lactic acid); pre-clinical; pressure; reconstruction; regeneration function; regenerative; scaffold; scale up; standard of care; stem cells; surgery outcome; tissue regeneration; tool; wireless electronic; wireless transmission

SUMMARY Each year in the United States, trauma, radiation therapy to treat urological cancers, severe cases of spina bifida, and interstitial cystitis contribute to at least 14,000 bladder augmentation enterocystoplasty surgeries. Although it is the standard of care for patients with an end-stage pathologic bladder, enterocystoplasty causes many complications due to anatomical and physiological differences between bladder tissue and the bowel tissue used to augment the bladder’s capacity. Several strategies have been reported to replace enterocystoplasty and regenerate bladder tissue but these have failed clinically. Reasons for the failure include the common use of phylogenetically dissimilar pre-clinical animal models that do not accurately represent the human bladder or its disease condition, the use of inadequate materials to serve as scaffolds for cells to grow on and regenerate bladder tissue, the use of often diseased autologous bladder cells that have lost the capacity to regenerate functional bladder tissue, and an inability to continuously monitor the tissue regeneration process to identify potential problems at an early stage. As a result, there is currently no viable alternative to augmentation enterocystoplasty. Regenerative engineering is a convergence of advanced material science, stem cell science, physics, and clinical translation. The overall goal of this project is to drive the development of unprecedented regenerative engineering tools and technologies via the integration of stem cell science, advanced biomaterials, and bio-integrated electronics to enable the regeneration of functional bladder tissue and the non-invasive, real-time assessment thereof to better predict outcome. Toward this goal, we have demonstrated our ability to: a) regenerate vascularized and innervated bladder tissue in a rat bladder augmentation model using a combination of bone marrow (BM) mesenchymal stem cells (MSCs), hematopoietic stem/progenitor cells (HSPCs), and an antioxidant citrate-based biodegradable elastomer, b) demonstrated successful bladder reconstruction with autologous cell-seeded POC scaffolds at 6 months in baboon; c) measure rat bladder pressure and control its function via a bio-integrated electronic strain gauge and light-activated excitatory channels, d) integrate stretchable electronics into citrate-based elastomers, and e) achieve wireless transmission of real time physiological data obtained in vivo using bio-integrated electronics. Towards our goal, the specific aims of this proposal are to: 1) Design, fabricate, and characterize bio-integrated electronics that monitor and modulate the function of regenerating bladder tissue via telemetry, 2) Engineer and characterize Stretch Monitoring Advanced Regenerative Telemetric (SMART) scaffolds for bladder augmentation, and 3) Assess the safety and efficacy of bladder conformal stretchable electronics and SMART scaffolds in a baboon bladder augmentation model.

概括 每年在美国，创伤，放射疗法治疗泌尿科癌症 裂和间质性膀胱炎至少有14,000个膀胱增强肠胃成形术手术。 尽管它是终末期病理膀胱的患者的护理标准，但肠胃成形术的原因 由于膀胱组织与肠道的解剖学和身体差异，许多并发症 组织用来增加膀胱的能力。据报道已有几种策略取代 肠囊泡成形术和再生膀胱组织，但这些组织在临床上失败了。失败的原因包括 无法准确代表的系统发育前临床前动物模型的常见使用 人膀​​胱或其疾病状况，使用不足的材料作为细胞生长的脚手架 在和再生膀胱组织中，使用丢失的经常失去的自体膀胱细胞的使用 再生功能性膀胱组织的能力，无法连续监测组织 再生过程以在早期识别潜在问题。结果，目前尚无可行 替代肠肠肠板膜成形术。再生工程是高级的融合 材料科学，干细胞科学，物理和临床翻译。该项目的总体目标是开车 通过STEM的整合开发前所未有的再生工程工具和技术 细胞科学，高级生物材料和生物集成电子产品，以实现功能的再生 膀胱组织及其无创的实时评估，以更好地预测结果。达到这个目标， 我们已经证明了我们的能力：a）在大鼠膀胱中再生血管化和神经支配的膀胱组织 使用骨髓（BM）间充质干细胞（MSC）的增强模型， 造血干/祖细胞（HSPCS）和基于柠檬酸的抗氧化剂可生物降解弹性体，b） 在6个月的自体细胞种子的POC支架中，已证明了成功的膀胱重建 狒狒; c）测量大鼠膀胱压力并通过生物集成电子应变量表来控制其功能 和光激活的兴奋通道，d）将可拉伸的电子设备整合到柠檬酸盐的弹性体中，以及 e）实现使用生物整合在体内获得的实时生理数据的无线传输 电子产品。为了我们的目标，该提案的具体目的是：1）设计，捏造和特征 通过遥测监测和调节再生膀胱组织的功能的生物集成电子产品， 2）工程师和表征拉伸监控的高级再生遥测（智能）脚手架 膀胱增大，3）评估膀胱共形性电子设备的安全性和效率 在狒狒膀胱增强模型中的智能脚手架。