Neufurth Meik, Wang Shunfeng, Schröder Heinz C, Al-Nawas Bilal, Wang Xiaohong, Müller Werner E G
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128 Mainz, Germany.
Clinic for Oral and Maxillofacial Surgery and Plastic Surgery, University Medical Center of the Johannes Gutenberg University, Augustusplatz 2, 55131 Mainz, Germany.
Biofabrication. 2021 Dec 31;14(1). doi: 10.1088/1758-5090/ac3f29.
The three-dimensional (3D)-printing processes reach increasing recognition as important fabrication techniques to meet the growing demands in tissue engineering. However, it is imperative to fabricate 3D tissue units, which contain cells that have the property to be regeneratively active. In most bio-inks, a metabolic energy-providing component is missing. Here a formulation of a bio-ink is described, which is enriched with polyphosphate (polyP), a metabolic energy providing physiological polymer. The bio-ink composed of a scaffold (-carboxymethyl chitosan), a hydrogel (alginate) and a cell adhesion matrix (gelatin) as well as polyP substantially increases the viability and the migration propensity of mesenchymal stem cells (MSC). In addition, this ink stimulates not only the growth but also the differentiation of MSC to mineral depositing osteoblasts. Furthermore, the growth/aggregate pattern of MSC changes from isolated cells to globular spheres, if embedded in the polyP bio-ink. The morphogenetic activity of the MSC exposed to polyP in the bio-ink is corroborated by qRT-PCR data, which show a strong induction of the steady-state-expression of alkaline phosphatase, connected with a distinct increase in the expression ratio between RUNX2 and Sox2. We propose that polyP should become an essential component in bio-inks for the printing of cells that retain their regenerative activity.
三维（3D）打印工艺作为满足组织工程中不断增长需求的重要制造技术，正日益受到认可。然而，制造包含具有再生活性细胞的3D组织单元势在必行。在大多数生物墨水中，缺少提供代谢能量的成分。本文描述了一种生物墨水的配方，其富含多聚磷酸盐（polyP），一种提供代谢能量的生理性聚合物。由支架（羧甲基壳聚糖）、水凝胶（藻酸盐）、细胞粘附基质（明胶）以及polyP组成的生物墨水显著提高了间充质干细胞（MSC）的活力和迁移倾向。此外，这种墨水不仅刺激MSC的生长，还刺激其向矿化成骨细胞的分化。此外，如果将MSC嵌入polyP生物墨水中，其生长/聚集模式会从分离的细胞转变为球形。生物墨水中暴露于polyP的MSC的形态发生活性得到qRT-PCR数据的证实，该数据显示碱性磷酸酶的稳态表达受到强烈诱导，同时RUNX2与Sox2之间的表达比率明显增加。我们认为，polyP应成为用于打印具有再生活性细胞的生物墨水中的必需成分。
