Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682041, India.
School of Chemical and Biological Engineering, Institute of Chemical Processes, BioMAX Institute, Seoul National University, Seoul, South Korea.
Int J Biol Macromol. 2019 Feb 1;122:320-328. doi: 10.1016/j.ijbiomac.2018.10.182. Epub 2018 Oct 26.
Functional biomaterials that couple angiogenesis and osteogenesis processes are vital for bone tissue engineering and bone remodeling. Herein we developed an injectable carrageenan nanocomposite hydrogel incorporated with whitlockite nanoparticles and an angiogenic drug, dimethyloxallylglycine. Synthesized whitlockite nanoparticles and nanocomposite hydrogels were characterized using SEM, TEM, EDS and FTIR. Developed hydrogels were injectable, mechanically stable, cytocompatible and has better protein adsorption. Incorporation of dimethyloxallylglycine resulted in initial burst release followed by sustained release for 7 days. Human umbilical vein endothelial cells exposed to dimethyloxallylglycine incorporated nanocomposite hydrogel showed enhanced cell migration and capillary tube-like structure formation. Osteogenic differentiation in rat adipose derived mesenchymal stem cells after 7 and 14 days revealed increased levels of alkaline phosphatase activity in vitro. Furthermore, cells exposed to nanocomposite hydrogel revealed enhanced protein expressions of RUNX2, COL and OPN. Overall, these results suggest that incorporation of whitlockite and dimethyloxallylglycine in carrageenan hydrogel promoted osteogenesis and angiogenesis in vitro.
用于骨组织工程和骨重塑的结合血管生成和成骨过程的功能性生物材料对于骨组织工程和骨重塑至关重要。在此，我们开发了一种可注射的卡拉胶纳米复合水凝胶，其中掺入了方镁石纳米粒子和一种血管生成药物，即草氨酸二甲酯。使用 SEM、TEM、EDS 和 FTIR 对合成的方镁石纳米粒子和纳米复合水凝胶进行了表征。开发的水凝胶具有可注射性、机械稳定性、细胞相容性和更好的蛋白质吸附性。草氨酸二甲酯的掺入导致初始突释，然后持续释放 7 天。暴露于含有草氨酸二甲酯的纳米复合水凝胶的人脐静脉内皮细胞显示出增强的细胞迁移和毛细血管样结构形成。在第 7 天和第 14 天，大鼠脂肪间充质干细胞的成骨分化显示出体外碱性磷酸酶活性的增加。此外，暴露于纳米复合水凝胶的细胞显示出 RUNX2、COL 和 OPN 的蛋白质表达增强。总的来说，这些结果表明，在卡拉胶水凝胶中掺入方镁石和草氨酸二甲酯可促进体外成骨和血管生成。
