Production of 3D Bioprinted Autologous Vaginal Tissue Constructs for Reconstructive Applications

生产用于重建应用的 3D 生物打印自体阴道组织结构

基本信息

批准号：
10672642
负责人：
James J Yoo
金额：
$ 61.22万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
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：
2023-06-10 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10672642
关键词：
3-Dimensional 3D Print Address Adult Anatomy Animal Model Animals Autologous Biocompatible Materials Biomanufacturing Biomechanics Biomedical Engineering Bladder Cartilage Cell Density Cell Separation Cells Child Childhood Clinical Clinical Trials Development Discipline of obstetrics Disease Dryness Epithelial Cells Epithelium Extracellular Matrix Female Goals Good Manufacturing Process Gynecologic Histologic Implant Intestines Libraries Malignant Neoplasms Mechanics Operative Surgical Procedures Organ Pathologic Pathway interactions Patient Care Patients Physiological Preparation Procedures Process Production Property Protocols documentation Quality Control Reconstructive Surgical Procedures Recording of previous events Regenerative Medicine Reproducibility Running Safety Series Skin Smooth Muscle Myocytes Standardization Technology Testing Therapeutic Tissue Engineering Tissue constructs Tissues Trauma Urethra Uterus Vagina Validation Work bioink biomaterial compatibility bioprinting bone clinical application clinically relevant fabrication innovation manufacture neovagina non-Native pediatric patients pre-clinical product development quality assurance reconstruction reproductive tract tissue reconstruction

项目摘要

PROJECT SUMMARY Many congenital and acquired conditions resulting in the abnormality of the vagina often require reconstructive surgery to achieve anatomical and physiological function. Unfortunately, reparative procedures are challenged by the availability of vaginal tissues. Unfortunately, the use of non-native vaginal tissues and biomaterial substitutes has contributed to various complications, including mechanical, structural, functional, or biocompatibility problems. It is evident that native vaginal tissue, with its inherent functional properties, is most suitable for surgical reconstruction. Recent advances in tissue engineering and regenerative medicine have provided a solution to create autologous tissues for various clinical applications, including skin, bone, cartilage, urethra, and bladder. Applying the principles of tissue engineering, we have previously applied bioengineered autologous neovaginal tissues to create a functionally normal vaginal vault in pediatric patients born with vaginal aplasia. Due to the varying levels of pathologic conditions in each patient, manufacturing the target bioengineered vaginal tissue construct for reconstruction is challenging, requiring a better solution to meet the clinical needs. 3D bioprinting technology has emerged as a solution to develop patient-specific personalized tissue constructs with precision and reproducibility, addressing the current translational limitation of biomanufacturing for wide reconstructive applications. To address this unmet clinical need, our central hypothesis is that developing a bioprinting workflow will permit the fabrication of personalized autologous vaginal tissue constructs for clinical use. Thus, the objective of this study is to establish a clinically applicable 3D bioprinting workflow to manufacture personalized autologous vaginal tissue constructs that consist of patient-derived vaginal epithelial cells (EPCs) and smooth muscle cells (SMCs) for vaginal tissue reconstruction. The central hypothesis will be tested by pursuing three Specific Aims: 1) Develop and optimize a bioprinting workflow to bioengineer a readily implantable vaginal tissue construct; 2) Validate the individualized bioprinted vaginal tissue constructs using a preclinical animal model; 3) Establish a process development and batch record for regulatory approval. Successful completion of the proposed work will provide a standardized 3D bioprinting workflow that generates personalized vaginal tissue constructs with the required precision for vaginal tissue reconstruction. Using personalized autologous bioengineered tissue constructs will significantly impact patient care and change how we approach vaginal reconstruction in growing children and adults.

项目概要许多先天性和后天性病症导致阴道异常，通常需要重建手术以实现解剖和生理功能。不幸的是，修复程序受到挑战通过阴道组织的可用性。不幸的是，使用非天然阴道组织和生物材料替代品导致了各种并发症，包括机械、结构、功能或生物相容性问题。显然，天然阴道组织以其固有的功能特性，是最重要的。适合手术重建。组织工程和再生医学的最新进展提供了一种为各种临床应用创建自体组织的解决方案，包括皮肤、骨骼、软骨、尿道、膀胱。应用组织工程的原理，我们之前已经应用了生物工程自体新阴道组织可为出生时阴道畸形的儿科患者创造功能正常的阴道穹窿发育不全。由于每个患者的病理状况水平不同，因此制造目标用于重建的生物工程阴道组织构建具有挑战性，需要更好的解决方案满足临床需要。 3D生物打印技术已成为开发针对特定患者的解决方案具有精确性和可重复性的个性化组织构建，解决了当前的翻译限制广泛的重建应用的生物制造。为了解决这一未满足的临床需求，我们的中心假设开发生物打印工作流程将允许制造个性化自体阴道供临床使用的组织结构。因此，本研究的目的是建立一个临床适用的3D 生物打印工作流程，用于制造个性化自体阴道组织结构，其中包括用于阴道组织的患者来源的阴道上皮细胞 (EPC) 和平滑肌细胞 (SMC) 重建。将通过追求三个具体目标来检验中心假设：1）开发和优化生物打印工作流程，用于生物工程设计易于植入的阴道组织结构； 2）验证个性化使用临床前动物模型构建生物打印的阴道组织； 3) 建立流程开发和批记录以供监管部门批准。成功完成拟议工作将提供标准化的 3D 生物打印工作流程，可生成具有阴道所需精度的个性化阴道组织结构组织重建。使用个性化自体生物工程组织构建体将显着影响患者护理并改变我们对成长中的儿童和成人进行阴道重建的方式。