Light-driven biofabrication of 3D stem-cell chondrogenic tissue analogues

3D 干细胞软骨形成组织类似物的光驱动生物制造

• 批准号: 2590196
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2590196
• 关键词: Light; driven; biofabrication; 3D; stem

Articular cartilage (AC) defects are one of the major causes of immobility and poor quality of life for millions of individuals worldwide. Current medical therapies have proven to be insufficient for the long-term regeneration of AC defects. Alternatively, the application of bioprinting in tissue engineering (TE) allows for the fabrication of complex 3D constructs via the precise spatial deposition of multiple cells and biomaterials. When integrated with human pluripotent stem cells (hPSCs), bioprinting opens up the possibility to generate human chondroprogenitor-containing tissue substitutes that can then be transplanted into AC defects and produce cartilage to repair the defect. cartilage. Despite significant progress, the current differentiation protocols for hPSCs towards chondrocytes still present several challenges, including the high cost, inducing factor batch to batch variation and precise timing of administered growth factors and cellular receptor expression together with poor precision of pathway activation. Based on previous work [1], we hypothesise that through using optogenetics, which combines optical and genetic approaches to control cell signalling and hence phenotype, cell-signalling receptors that are critical for regulation of chondrogenesis can be replaced with engineered light sensitive receptors, allowing activation of signalling by specific light wavelengths. This will enable precision fine-tuning of differentiation in 3D bioprinted cell-laden hydrogels by light. If successful, this innovative approach would enable, for the first time, the dynamic manipulation of cell signalling pathways with high spatio-temporal precision.

关节软骨 (AC) 缺陷是全球数百万人行动不便和生活质量差的主要原因之一。目前的医学疗法已被证明不足以实现 AC 缺陷的长期再生。或者，生物打印在组织工程 (TE) 中的应用允许通过多个细胞和生物材料的精确空间沉积来制造复杂的 3D 结构。当与人类多能干细胞 (hPSC) 整合时，生物打印开启了生成含有人类软骨祖细胞的组织替代品的可能性，然后将其移植到 AC 缺损处并产生软骨来修复缺损。软骨。尽管取得了重大进展，目前 hPSC 向软骨细胞的分化方案仍然面临一些挑战，包括高成本、诱导因子批次之间的变化、施用生长因子和细胞受体表达的精确时间以及途径激活的精度差。基于之前的工作[1]，我们假设通过使用光遗传学（结合光学和遗传方法来控制细胞信号传导和表型），对软骨形成调节至关重要的细胞信号传导受体可以被工程化的光敏受体取代，从而允许通过特定的光波长激活信号传导。这将能够通过光对 3D 生物打印的充满细胞的水凝胶的分化进行精确微调。如果成功，这种创新方法将首次能够以高时空精度动态操纵细胞信号通路。