Online Monitoring and Control of Functional Cartilage Regeneration in Hydrogels

水凝胶中功能性软骨再生的在线监测和控制

• 批准号: 7125475
• 负责人: KRISTI S. ANSETH
• 金额: $ 24.18万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-25 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125475
• 关键词: bioengineering /biomedical engineering; biofeedback; biomaterials; biomechanics; bioreactors; cartilage; chondrocytes; extracellular matrix; gel; lipase; microscopy; musculoskeletal disorder; polyethylene glycols; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): The engineering of functionally competent cartilage depends significantly on the biochemical and mechanical environment in which the tissue-engineered (TE) construct develops. Our long-term objective is to optimize the functional tissue engineering of cartilage as a step toward increasing the availability of regenerative and reparative treatments for patients with musculoskeletal disorders such as osteoarthritis. The specific hypothesis is that biomechanical properties of TE cartilage can be optimized if control of scaffold degradation and mechanical stimulation combined with online ultrasonic imaging and monitoring capabilities are integrated into a bioreactor design. We base this hypothesis on the observations that 1) copolymer gel scaffolds with bimodal degradation profiles improve distribution of extracellular matrix (ECM) molecules while maintaining mechanical properties of the initial hydrogel, 2) high-frequency ultrasound is sensitive to ECM content, and 3) mechanical stimulation of engineered cartilage leads to improved biosynthesis and functionality. Based on these observations, we take a multi-disciplinary science and engineering approach to improve the quality of TE cartilage. The specific aims are to: 1. Incorporate triggerable markers into a poly(ethylene glycol) based hydrogel with encapsulated chondrocytes in order to permit control of the degradation profile of the polymer scaffold as the tissue-engineered cartilage evolves. We will characterize the degradation profiles of these hydrogels in response to an exogenously delivered lipase enzyme, and we will quantify ECM production and distribution when chondrocytes are encapsulated in these hydrogels. 2. Measure and model the mechanical and ultrasonic properties of TE cartilage and bovine articular cartilage to enable online monitoring of the quality of TE cartilage. We will establish target properties for TE cartilage based on acoustic microscopy measurements of immature bovine cartilage. A quality index for ECM production in TE cartilage will be based on a combination of multiple ultrasonic and mechanical parameters determined from experimental measurements and numerical models. 3. Design a bioreactor for tissue engineering of cartilage with feedback control capabilities to optimize quality of the TE cartilage. We will integrate quantitative ultrasonic imaging and measurement capabilities into the bioreactor to monitor the quality of the developing TE cartilage. We will incorporate feedback control using a heuristic control loop to modify the biochemical and mechanical environment in order to optimize ECM production.

描述（由申请人提供）：功能软骨的工程很大程度上取决于组织工程（TE）构建体发育的生化和机械环境。我们的长期目标是优化软骨的功能组织工程，以提高骨关节炎等肌肉骨骼疾病患者的再生和修复治疗的可用性。具体假设是，如果将支架降解和机械刺激的控制与在线超声成像和监测功能集成到生物反应器设计中，则可以优化 TE 软骨的生物力学特性。我们的假设基于以下观察结果：1) 具有双峰降解曲线的共聚物凝胶支架改善细胞外基质 (ECM) 分子的分布，同时保持初始水凝胶的机械性能，2) 高频超声对 ECM 含量敏感，3)工程软骨的机械刺激可改善生物合成和功能。基于这些观察，我们采用多学科科学和工程方法来提高 TE 软骨的质量。具体目标是： 1. 将可触发标记物纳入具有封装软骨细胞的聚乙二醇水凝胶中，以便随着组织工程软骨的演化控制聚合物支架的降解情况。我们将表征这些水凝胶响应外源传递的脂肪酶的降解曲线，并且我们将量化当软骨细胞封装在这些水凝胶中时 ECM 的产生和分布。 2. 对TE软骨和牛关节软骨的力学和超声特性进行测量和建模，实现TE软骨质量的在线监测。我们将根据未成熟牛软骨的声学显微镜测量确定 TE 软骨的目标特性。 TE 软骨 ECM 生产的质量指数将基于根据实验测量和数值模型确定的多个超声波和机械参数的组合。 3. 设计用于软骨组织工程的生物反应器，具有反馈控制功能，以优化 TE 软骨的质量。我们将把定量超声成像和测量功能集成到生物反应器中，以监测正在发育的 TE 软骨的质量。我们将使用启发式控制回路结合反馈控制来修改生化和机械环境，以优化 ECM 生产。