Xiao Hugh, Liang Zixie, Gong Xiangyu, Jordan Seyma Nayir, Rossello-Martinez Alejandro, Gokhan Ilhan, Li Xia, Wen Zhang, Lee Sein, Campbell Stuart G, Qyang Yibing, Mak Michael
Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06520, USA.
APL Bioeng. 2025 Jun 12;9(2):026124. doi: 10.1063/5.0252746. eCollection 2025 Jun.
Advancing cardiac tissue engineering requires innovative fabrication techniques, including 3D bioprinting and tissue maturation, to enable the generation of new muscle for repairing or replacing damaged heart tissue. Recent advances in tissue engineering have highlighted the need for rapid, high-resolution bioprinting methods that preserve cell viability and maintain structural fidelity. Traditional collagen-based bioinks gel slowly, limiting their use in bioprinting. Here, we implement TRACE (tunable rapid assembly of collagenous elements), a macromolecular crowding-driven bioprinting technique that enables the immediate gelation of collagen bioinks infused with cells. This overcomes the need for extended incubation, allowing for direct bioprinting of engineered cardiac tissues with high fidelity. Unlike methods that rely on high-concentration acidic collagen or fibrin for gelation, TRACE achieves rapid bioink stabilization without altering the biochemical composition. This ensures greater versatility in bioink selection while maintaining functional tissue outcomes. Additionally, agarose slurry provides stable structural support, preventing tissue collapse while allowing nutrient diffusion. This approach better preserves complex tissue geometries during culture than gelatin-based support baths or polydimethylsiloxane (PDMS) molds. Our results demonstrate that TRACE enables the bioprinting of structurally stable cardiac tissues with high resolution. By supporting the fabrication of biomimetic tissues, TRACE represents a promising advancement in bioprinting cardiac models and other engineered tissues.
推进心脏组织工程需要创新的制造技术,包括3D生物打印和组织成熟,以生成新的肌肉来修复或替换受损的心脏组织。组织工程的最新进展凸显了对快速、高分辨率生物打印方法的需求,这些方法要能保持细胞活力并维持结构保真度。传统的基于胶原蛋白的生物墨水凝胶化缓慢,限制了它们在生物打印中的应用。在此,我们采用了TRACE(可调节的胶原元素快速组装)技术,这是一种由大分子拥挤驱动的生物打印技术,能使注入细胞的胶原蛋白生物墨水立即凝胶化。这克服了长时间孵育的需求,允许以高保真度直接生物打印工程化心脏组织。与依靠高浓度酸性胶原蛋白或纤维蛋白进行凝胶化的方法不同,TRACE在不改变生化成分的情况下实现了生物墨水的快速稳定。这确保了在生物墨水选择上有更大的通用性,同时维持功能性组织结果。此外,琼脂糖浆料提供了稳定的结构支撑,防止组织塌陷,同时允许营养物质扩散。与基于明胶的支撑浴或聚二甲基硅氧烷(PDMS)模具相比,这种方法在培养过程中能更好地保留复杂的组织几何形状。我们的结果表明,TRACE能够以高分辨率生物打印结构稳定的心脏组织。通过支持仿生组织的制造,TRACE代表了生物打印心脏模型和其他工程组织方面的一项有前景的进展。