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

项目总结 许多导致阴道异常的先天性和后天性疾病常常需要重建。 达到解剖和生理功能的外科手术。不幸的是，修复程序受到了挑战。 由阴道组织的可用性决定的。不幸的是，非天然阴道组织和生物材料的使用 替代品导致了各种并发症，包括机械的、结构的、功能的或 生物兼容性问题。显然，天然的阴道组织，具有其固有的功能特性，是最 适用于外科重建。组织工程和再生医学的最新进展 提供了一种解决方案来创建各种临床应用的自体组织，包括皮肤、骨、软骨、 尿路和膀胱。应用组织工程的原理，我们以前已经应用了生物工程 自体新阴道组织在先天性阴道儿中建立功能正常的阴道穹隆 再生障碍症。由于每个患者的病理条件程度不同，制造靶子 构建用于重建的生物工程阴道组织具有挑战性，需要更好的解决方案 满足临床需求。3D生物打印技术已经作为一种解决方案出现，以开发针对患者的 具有精确度和重复性的个性化组织结构，解决了目前的翻译限制 用于广泛的重建应用的生物制造。为了解决这一未得到满足的临床需求，我们的中央 假设是，开发生物打印工作流程将允许制造个性化的自体阴道 临床使用的组织结构。因此，本研究的目的是建立一种临床适用的3D 生物印刷工作流程以制造个性化的自体阴道组织构造物，其包括 患者来源的阴道上皮细胞(EPC)和阴道组织的平滑肌细胞(SMC) 重建。核心假设将通过追求三个具体目标来检验：1)发展和优化 生物打印工作流程，以生物工程的容易植入的阴道组织结构；2)验证个性化 Biopprint阴道组织使用临床前动物模型构建；3)建立一个过程开发和 用于监管部门审批的批次记录。拟议工作的成功完成将提供标准化的3D 生物打印工作流程，生成个性化的阴道组织结构，具有阴道所需的精度 组织重建。使用个性化的自体生物工程组织结构将显著影响 患者护理和改变我们在成长中的儿童和成人进行阴道重建的方式。

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.