Stengelin Elena, Kuzmina Alena, Beltramo Guillermo L, Koziol Martha F, Besch Laura, Schröder Romina, Unger Ronald E, Tremel Wolfgang, Seiffert Sebastian
Johannes Gutenberg University Mainz, Department of Chemistry, Mainz, D-55128, Germany.
Institute of Biological Information Processing 2 (IBI-2), Jülich Forschungszentrum GmbH, Jülich, D-52428, Germany.
Adv Healthc Mater. 2020 Jun;9(11):e1901820. doi: 10.1002/adhm.201901820. Epub 2020 May 6.
Vaterite, a metastable modification of calcium carbonate, embedded in a flexible microgel packaging with adjustable mechanical properties, functionality, and biocompatibility, provides a powerful scaffolding for bone tissue regeneration, as it is easily convertible to bone-like hydroxyapatite (HA). In this study, the synthesis and physical analysis of a packaging material to encapsulate vaterite particles and osteoblast cells into monodisperse, sub-millimeter-sized microgels, is described whereby a systematic approach is used to tailor the microgel properties. The size and shape of the microgels is controlled via droplet-based microfluidics. Key requirements for the polymer system, such as absence of cytotoxicity as well as biocompatibility and biodegradability, are accomplished with functionalized poly(ethylene glycol) (PEG), which reacts in a cytocompatible thiol-ene Michael addition. On a mesoscopic level, the microgel stiffness and gelation times are adjusted to obtain high cellular viabilities. The co-encapsulation of living cells provides i) an in vitro platform for the study of cellular metabolic processes which can be applied to bone formation and ii) an in vitro foundation for novel tissue-regenerative therapies. Finally, the degradability of the microgels at physiological conditions caused by hydrolysis-sensitive ester groups in the polymer network is examined.
球霰石是碳酸钙的一种亚稳态变体，嵌入具有可调节机械性能、功能和生物相容性的柔性微凝胶包装中，为骨组织再生提供了强大的支架，因为它很容易转化为骨样羟基磷灰石（HA）。在本研究中，描述了一种包装材料的合成和物理分析，该材料将球霰石颗粒和成骨细胞封装到单分散的亚毫米级微凝胶中，采用系统方法来调整微凝胶的性能。微凝胶的尺寸和形状通过基于液滴的微流控技术进行控制。聚合物体系的关键要求，如无细胞毒性以及生物相容性和生物降解性，通过功能化聚乙二醇（PEG）来实现，其在细胞相容的硫醇-烯迈克尔加成反应中发生反应。在介观水平上，调整微凝胶的硬度和凝胶化时间以获得高细胞活力。活细胞的共封装提供了：i）一个用于研究可应用于骨形成的细胞代谢过程的体外平台，以及ii）新型组织再生疗法的体外基础。最后，研究了聚合物网络中对水解敏感的酯基导致的微凝胶在生理条件下的降解性。
