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三维（3D）组织的培养物。 Flexcell的策略是提供一种商业生物反应器，以便于在可变几何形状的细胞填充矩阵凝胶中产生模制的3D组织构建体，并具有受控的营养灌注和机械刺激。该设计基于经过验证的，经过压力的平台技术，具有扩展的，组织（TM）3D培养系统，以允许单个研究团队研究“最佳”技术和方法，以开发和整合特定的组织。该项目的长期目标包括精炼和自动化生物反应器，以开发用于再生医学的组织替换。将替换材料由模板模具和锚定制造，允许宿主整合。 II期装置将具有其他传感器，可以监测生物人工组织的发展，包括O2，CO2，PH，离子强度，特定代谢物，构建体的大小，形状和密度，甚至被细菌或病毒污染。具体目的包括：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端增加的接触表面积的影响，扩散约束作为组织的扩散约束，以及在构造中与构造中产生的菌株的菌株，将其应用于机械条件，以使新生组织的机械状态。 2。根据Fletcell的柔性底部培养板（Tissuortain（TM））平台建立的基于缩放3D组织生物反应器和组织锚固/集成系统的FEA模拟的结果开发植物设计。锚端设计将包括更多涉及的3D实施方案，这些实施方案允许增加键合和宿主积分的几何形状，用于细胞和基质。 3。使用ATCC细胞系和有限的结果参数（例如基质表达，凝胶基质的重塑和生物力学强度的重塑），使用线性（前交叉韧带）和圆形（真皮皮肤构建体）的示例。韧带细胞和皮肤成纤维细胞将用于制造可在生物反应器中原位监测的线性和圆形3D细胞构建体。该生物反应器的研究版本已经在Flexcell International Corp上在商业上可用。扩展到更大的生物反应室将使生物医学研究人员能够制定更好的策略，用于在众多结缔组织应用中使用缩放的组织在体内使用缩放的组织。