Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen, 9747 AG, The Netherlands.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands.
Adv Mater. 2023 Jul;35(28):e2210769. doi: 10.1002/adma.202210769. Epub 2023 May 31.
3D bioprinting is a powerful fabrication technique in biomedical engineering, which is currently limited by the number of available materials that meet all physicochemical and cytocompatibility requirements for biomaterial inks. Inspired by the key role of coacervation in the extrusion and spinning of many natural materials, hyaluronic acid-chitosan complex coacervates are proposed here as tunable biomaterial inks. Complex coacervates are obtained through an associative liquid-liquid phase separation driven by electrostatic attraction between oppositely charged macromolecules. They offer bioactive properties and facile modulation of their mechanical properties through mild physicochemical changes in the environment, making them attractive for 3D bioprinting. Fine-tuning the salt concentration, pH, and molecular weight of the constituent polymers results in biomaterial inks that are printable in air and water. The biomaterial ink, initially a viscoelastic fluid, transitions into a viscoelastic solid upon printing due to dehydration (for printing in air) or due to a change in pH and ionic composition (for printing in solution). Consequently, scaffolds printed using the complex coacervate inks are stable without the need for post-printing processing. Fabricated cell culture scaffolds are cytocompatible and show long-term topological stability. These results pave the way to a new class of easy-to-handle tunable biomaterials for biofabrication.
3D 生物打印是生物医学工程中的一种强大制造技术，目前受到能够满足生物材料墨水所有物理化学和细胞相容性要求的可用材料数量的限制。受许多天然材料在挤压和纺丝过程中凝聚作用的关键作用的启发，本文提出了透明质酸-壳聚糖复合凝聚物作为可调生物材料墨水。复合凝聚物是通过带相反电荷的大分子之间的静电吸引驱动的缔合液-液相分离获得的。它们具有生物活性，并可通过环境中温和的物理化学变化轻松调节其机械性能，因此它们对 3D 生物打印具有吸引力。精细调节组成聚合物的盐浓度、pH 值和分子量，可得到在空气中和水中都可打印的生物材料墨水。由于脱水（用于空气打印）或由于 pH 值和离子组成的变化（用于溶液打印），生物材料墨水最初为粘弹性流体，在打印后转变为粘弹性固体。因此，使用复合凝聚物墨水打印的支架无需后处理即可稳定。制造的细胞培养支架具有细胞相容性，并表现出长期的拓扑稳定性。这些结果为生物制造中易于处理的可调生物材料开辟了新途径。
