Loukelis Konstantinos, Kontogianni Georgia-Ioanna, Vlassopoulos Dimitris, Chatzinikolaidou Maria
Department of Materials Science and Engineering, University of Crete, Heraklion, 70013, Greece.
Foundation for Research and Technology Hellas (FORTH)-Institute of Electronic Structure and Laser (IESL), Heraklion, 70013, Greece.
Adv Healthc Mater. 2025 Jul;14(19):e2500365. doi: 10.1002/adhm.202500365. Epub 2025 Jun 2.
3D bioprinting is a versatile technology using bioinks comprising living cells mixed with biomaterials and biomolecules to biofabricate structures with precise spatial hierarchy. Based on this principle, novel 3D bioprinted constructs are designed, comprising the natural anionic polysaccharide gellan gum (GG), the synthetic polymer poly(vinyl alcohol) (PVA), and pre-osteoblastic cells. Moreover, nano-hydroxyapatite (nHA) is included to the GG/PVA blend as an osteoinductive biomaterial. The integration of nHA led to significantly improved printing accuracy, while the rheological evaluation showed that all bioinks exhibited shear-thinning properties and viscosity recovery capability close to 90%. Biodegradation studies revealed reduced mass loss rates of up to 16% in the presence of nHA, compared to those of the GG/PVA control at 27%, after 3 weeks. Biocompatibility data correlate to the material stiffness, with lower GG concentration bioinks retaining cell viability higher than 85% after 7 days, while higher GG concentration counterparts showed values close to 50%. The osteogenic capacity of lower GG concentration bioinks are monitored through alkaline phosphatase, calcium, and collagen production, and osteogenic gene expression analysis, showing a significant upregulation in nHA-containing bioinks. The results demonstrate that the nHA bioinks display viscoelastic properties and biological response suitable for bone tissue engineering applications.
3D生物打印是一种多功能技术，它使用由活细胞与生物材料和生物分子混合而成的生物墨水，来生物制造具有精确空间层次结构的结构。基于这一原理，设计了新型的3D生物打印构建体，其包含天然阴离子多糖结冷胶（GG）、合成聚合物聚乙烯醇（PVA）和成骨前体细胞。此外，纳米羟基磷灰石（nHA）作为一种骨诱导生物材料被添加到GG/PVA混合物中。nHA的加入显著提高了打印精度，而流变学评估表明，所有生物墨水都表现出剪切变稀特性和接近90%的粘度恢复能力。生物降解研究表明，在3周后，与GG/PVA对照组27%的质量损失率相比，在存在nHA的情况下，质量损失率降低至16%。生物相容性数据与材料硬度相关，较低GG浓度的生物墨水在7天后保持高于85%的细胞活力，而较高GG浓度的生物墨水则显示接近50%的值。通过碱性磷酸酶、钙和胶原蛋白的产生以及成骨基因表达分析来监测较低GG浓度生物墨水的成骨能力，结果显示含nHA的生物墨水中有显著上调。结果表明，nHA生物墨水表现出适合骨组织工程应用的粘弹性特性和生物学反应。
