Bioreactor for Engineered Bioartificial Tissues (BATS)

工程生物人工组织生物反应器 (BATS)

基本信息

批准号：
7052490
负责人：
ALBERT J BANES
金额：
$ 10万
依托单位：
FLEXCELL INTERNATIONAL CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-06 至 2008-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7052490
关键词：
bioengineering /biomedical engineering biomaterial development /preparation biomaterial evaluation biomechanics biomedical automation bioreactors biotechnology connective tissue development fibroblasts ligaments mathematical model skin tissue engineering total artificial organ

项目摘要

DESCRIPTION (provided by applicant): Few commercial bioreactors are available for the culture of three dimensional (3D) tissues. Flexcell's strategy is to provide a commercial bioreactor allowing ease of operation to produce molded 3D tissue constructs in cell- populated matrix gels of variable geometries with controlled nutrient perfusion and mechanical stimulation. This design is based on a validated, pressure-operated platform technology with a scaled-up, TissueTrain(tm) 3D culture system, to allow individual research teams to investigate "best" techniques and methods to develop and integrate specific tissues. Long-term goals of the project include refining and automating the bioreactor to develop tissue replacements for regenerative medicine. Tissue replacements will be fabricated from template molds and anchors allowing host integration. The Phase II device will have additional sensors that can monitor the development of the bioartificial tissue, including O2, CO2, pH, ionic strength, specific metabolites, construct size, shape and density and even contamination with bacteria or viruses. Specific Aims include: 1. use finite element modeling of key design features to predict effects of increased contact surface areas at tissue anchor ends in each bioreactor chamber, diffusion constraints as a tissue is scaled-up, as well as the strains generated with in the construct as force is applied to mechanicaly condition the nascent tissue. 2. develop inerative designs based on results of FEA simulations for a scaled-up 3D tissue bioreactor and tissue anchor/integration system built on Flexcell's flexible bottom culture plate (TissueTrain(tm)) platform using tissue molding for fabrication and mechanical loading to condition the constructs. The anchor end designs will include more involved 3D embodiments that allow increased bonding and host integration geometries for cells and matrix. 3. fabricate examples of linear (anterior cruciate ligament) and circular (dermal skin construct) 3D constructs using ATCC cell lines and monitor limited outcome parameters such as matrix expression, remodeling of the gel matrix and biomechanical strength. Ligament cells and dermal fibroblasts will be used to fabricate linear and circular 3D cell- gel constructs that can be monitored in situ in the bioreactor. The research version of this bioreactor is already commercially available by Flexcell International Corp. Expansion to a larger bioreactor chamber will allow biomedical researchers to develop better strategies for growth and testing of scaled up tissues for use in vivo in numerous connective tissue applications.

描述（由申请人提供）：很少有商业生物反应器可用于培养三维（3D）组织。 Flexcell 的战略是提供一种商业生物反应器，可以轻松操作，在具有受控营养物灌注和机械刺激的可变几何形状的细胞填充基质凝胶中生产模制 3D 组织结构。该设计基于经过验证的压力操作平台技术，具有放大的 TissueTrain(tm) 3D 培养系统，允许各个研究团队研究“最佳”技术和方法来开发和整合特定组织。该项目的长期目标包括改进和自动化生物反应器，以开发再生医学的组织替代品。组织替代物将由模板模具和允许宿主集成的锚定件制成。 II 期设备将配备额外的传感器，可以监测生物人工组织的发育，包括 O2、CO2、pH、离子强度、特定代谢物、结构尺寸、形状和密度，甚至细菌或病毒的污染。具体目标包括： 1. 使用关键设计特征的有限元建模来预测每个生物反应器室中组织锚定端接触表面积增加的影响、组织按比例放大时的扩散约束以及在组织中产生的应变。当施加力以机械方式调节新生组织时构建。 2. 基于 FEA 模拟结果，开发基于 Flexcell 柔性底部培养板 (TissueTrain(tm)) 平台的放大 3D 组织生物反应器和组织锚定/集成系统的惯性设计，使用组织成型进行制造和机械加载以调节构造。锚端设计将包括更多涉及的3D实施例，允许增加细胞和基质的结合和主体集成几何形状。 3. 使用 ATCC 细胞系制造线性（前十字韧带）和圆形（真皮构建体）3D 构建体的示例，并监测有限的结果参数，例如基质表达、凝胶基质的重塑和生物力学强度。韧带细胞和真皮成纤维细胞将用于制造线性和圆形 3D 细胞凝胶结构，可以在生物反应器中进行原位监测。该生物反应器的研究版本已由 Flexcell International Corp 投入商业销售。扩展到更大的生物反应器室将使生物医学研究人员能够开发更好的策略来生长和测试放大的组织，以便在体内用于多种结缔组织应用。