Twohig Chelsea, Helsinga Mari, Mansoorifar Amin, Athirasala Avathamsa, Tahayeri Anthony, França Cristiane Miranda, Pajares Silvia Amaya, Abdelmoniem Reyan, Scherrer Susanne, Durual Stéphane, Ferracane Jack, Bertassoni Luiz E
Department of Periodontology, School of Dentistry, Oregon Health and Science University, OR, USA.
Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, OR, USA.
Mater Sci Eng C Mater Biol Appl. 2021 Apr;123:111976. doi: 10.1016/j.msec.2021.111976. Epub 2021 Feb 15.
A functional vascular supply is a key component of any large-scale tissue, providing support for the metabolic needs of tissue-remodeling cells. Although well-studied strategies exist to fabricate biomimetic scaffolds for bone regeneration, success rates for regeneration in larger defects can be improved by engineering microvascular capillaries within the scaffolds to enhance oxygen and nutrient supply to the core of the engineered tissue as it grows. Even though the role of calcium and phosphate has been well understood to enhance osteogenesis, it remains unclear whether calcium and phosphate may have a detrimental effect on the vasculogenic and angiogenic potential of endothelial cells cultured on 3D printed bone scaffolds. In this study, we presented a novel dual-ink bioprinting method to create vasculature interwoven inside CaP bone constructs. In this method, strands of a CaP ink and a sacrificial template material was used to form scaffolds containing CaP fibers and microchannels seeded with vascular endothelial and mesenchymal stem cells (MSCs) within a photo-crosslinkable gelatin methacryloyl (GelMA) hydrogel material. Our results show similar morphology of growing vessels in the presence of CaP bioink, and no significant difference in endothelial cell sprouting was found. Furthermore, our initial results showed the differentiation of hMSCs into pericytes in the presence of CaP ink. These results indicate the feasibility of creating vascularized bone scaffolds, which can be used for enhancing vascular formation in the core of bone scaffolds.
功能性血管供应是任何大规模组织的关键组成部分，为组织重塑细胞的代谢需求提供支持。尽管存在用于制造骨再生仿生支架的经过充分研究的策略，但通过在支架内构建微血管毛细血管以在工程组织生长时增强向其核心的氧气和营养供应，可以提高较大缺损再生的成功率。尽管钙和磷在促进骨生成方面的作用已得到充分理解，但钙和磷是否可能对在3D打印骨支架上培养的内皮细胞的血管生成和血管形成潜力产生不利影响仍不清楚。在本研究中，我们提出了一种新型双墨水生物打印方法，以在磷酸钙（CaP）骨构建体内部创建交织的血管系统。在这种方法中，CaP墨水和牺牲模板材料的细丝用于在可光交联的甲基丙烯酰化明胶（GelMA）水凝胶材料内形成含有CaP纤维和接种有血管内皮细胞和间充质干细胞（MSCs）的微通道的支架。我们的结果表明，在存在CaP生物墨水的情况下，生长血管的形态相似，并且在内皮细胞发芽方面未发现显著差异。此外，我们的初步结果表明，在存在CaP墨水的情况下，人间充质干细胞（hMSCs）可分化为周细胞。这些结果表明创建血管化骨支架的可行性，其可用于增强骨支架核心中的血管形成。
