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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(申请人提供)：几乎没有商用生物反应器可用于三维(3D)组织的培养。Flexell的战略是提供一种商业生物反应器，使其易于操作，在细胞填充的不同几何形状的基质凝胶中生产成型的3D组织结构，并控制营养灌流和机械刺激。这一设计基于经过验证的压力操作平台技术，以及放大的TIssueTrain(Tm)3D培养系统，使各个研究团队能够研究开发和整合特定组织的“最佳”技术和方法。该项目的长期目标包括改进和自动化生物反应器，以开发用于再生医学的组织替代物。组织替代物将由模板模具和锚制成，允许宿主整合。二期设备将配备额外的传感器，可以监控生物人造组织的发育，包括氧气、二氧化碳、pH、离子强度、特定代谢物、结构大小、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内组织锚端处接触表面积增加的影响，当组织放大时的扩散约束，以及当力被应用于新生组织的机械条件时在结构中产生的应变。2.根据有限元模拟的结果，开发基于Flexell的柔性底部培养板(TIssueTrain(Tm))平台的放大3D组织生物反应器和组织锚/集成系统的惯性设计，使用组织成型制造和机械加载来调节构建物。锚端设计将包括更复杂的3D实施例，其允许增加单元和基质的结合和主体集成几何形状。3.使用ATCC细胞系制作线形(前十字韧带)和圆形(真皮结构)三维结构的例子，并监测有限的结果参数，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被用来制造线性和圆形的3D细胞凝胶结构，可以在生物反应器中进行原位监测。这种生物反应器的研究版本已经由Flexell International Corp.商业化，扩展到一个更大的生物反应器舱将使生物医学研究人员能够开发出更好的策略，用于扩大组织的生长和测试，用于体内的许多结缔组织应用。