Ceccaldi Caroline, Assaad Elias, Hui Eve, Buccionyte Medeine, Adoungotchodo Atma, Lerouge Sophie
Department of Mechanical Engineering, Ecole de technologie supérieure, 1100 Notre-Dame Ouest, Montréal, QC, H3C 1K3, Canada.
CHUM Research Center (CRCHUM), Tour Viger, 900 rue Saint-Denis, Montréal, QC, H2X 0A9, Canada.
Macromol Biosci. 2017 Jun;17(6). doi: 10.1002/mabi.201600435. Epub 2017 Jan 24.
Strong injectable chitosan thermosensitive hydrogels can be created, without chemical modification, by combining sodium hydrogen carbonate with another weak base, namely, beta-glycerophosphate (BGP) or phosphate buffer (PB). Here the influence of gelling agent concentration on the mechanical properties, gelation kinetics, osmolality, swelling, and compatibility for cell encapsulation, is studied in order to find the most optimal formulations and demonstrate their potential for cell therapy and tissue engineering. The new formulations present up to a 50-fold increase of the Young's modulus after gelation compared with conventional chitosan-BGP hydrogels, while reducing the ionic strength to the level of iso-osmolality. Increasing PB concentration accelerates gelation but reduces the mechanical properties. Increasing BGP also has this effect, but to a lesser extent. Cells can be easily encapsulated by mixing the cell suspension within the hydrogel solution at room temperature, prior to rapid gelation at body temperature. After encapsulation, L929 mouse fibroblasts are homogeneously distributed within scaffolds and present a strongly increased viability and growth, when compared with conventional chitosan-BGP hydrogels. Two particularly promising formulations are evaluated with human mesenchymal stem cells. Their viability and metabolic activity are maintained over 7 d in vitro.
通过将碳酸氢钠与另一种弱碱，即β-甘油磷酸酯（BGP）或磷酸盐缓冲液（PB）混合，可以在不进行化学修饰的情况下制备出强力可注射壳聚糖热敏水凝胶。在此，研究了胶凝剂浓度对机械性能、凝胶化动力学、渗透压、溶胀以及细胞包封兼容性的影响，以便找到最优化的配方，并证明其在细胞治疗和组织工程中的潜力。与传统的壳聚糖-BGP水凝胶相比，新配方在凝胶化后杨氏模量提高了50倍，同时将离子强度降低到等渗水平。增加PB浓度会加速凝胶化，但会降低机械性能。增加BGP也有这种效果，但程度较小。在体温下快速凝胶化之前，通过在室温下将细胞悬液与水凝胶溶液混合，可以轻松地将细胞包封起来。包封后，与传统的壳聚糖-BGP水凝胶相比，L929小鼠成纤维细胞在支架内均匀分布，活力和生长显著增加。用人间充质干细胞对两种特别有前景的配方进行了评估。它们的活力和代谢活性在体外7天内得以维持。
