Calcium carbonate material is a common inorganic non-metallic material in the field of biomedicine. The research and application directions have covered many aspects, such as: the way of entering cells, distribution in cells, cytotoxicity, genotoxicity and drug release, Biomaterial preparation, etc. When the ultra-fine nano-calcium carbonate material “encounters” stem cells, what sparks can they create?
1. Nano calcium carbonate “breaks through” the bottleneck of stem cell culture technology
At present, there are two types of stem cell culture modes: 2D (traditional) culture and 3D culture. The 2D stem cell culture model is relatively simple, but cannot accurately describe and simulate the rich environment and complex processes in the body, such as signal transduction, spatial structure changes, etc.; and the technology tends to mature, it is difficult to achieve large-scale stem cell culture. The 3D stem cell culture technology is completed in a three-dimensional container, which can independently regulate the composition of the culture medium, realize the large-scale culture of stem cells, and even be applied to the research of in vitro organoid formation. At present, 3D culture has gradually become the mainstream technology of the stem cell industry chain. .
However, in the 3D stem cell culture technology chain, the most important “carrier” is still the key element restricting its industrial development. At present, many manufacturers conduct research and development of stem cell 3D culture carriers, but most of them use organic solvents, including benzene, as pore-forming agents when manufacturing stem cell 3D culture carriers, especially porous microcarriers, which have potential harm to the cultured stem cells. Therefore, a friendly porogen is urgently needed.
Recently, Hua Ziang provided a microcarrier for 3D culture simulating stem cell nests and its preparation method. In essence, the calcium carbonate material that is friendly to stem cells is used as a porogen, and the calcium carbonate is dissolved and removed by dilute acid to form the internal pores of the carrier. No organic solvent is used in the manufacturing process of the carrier for stem cell 3D culture, which effectively avoids the use of volatilization to remove causative agents. The problem of residual organic solvent in stem cell 3D culture carrier caused by organic solvent for pores.
2. Nano calcium carbonate promotes stem cell proliferation
At present, stem cell therapy technology has shown great clinical application prospects in gene therapy, autoimmune disease, brain and nervous system disease treatment, and cardiovascular disease treatment. Among them, the advantages of autologous adult stem cell transplantation are particularly prominent. However, adult stem cells are limited in number in the body and need to be expanded in vitro to meet clinical needs. The traditional plate culture has the phenomenon of contact inhibition, the cell proliferation rate is low, and it is easy to differentiate or age, which seriously affects the quantity and quality of stem cells. Therefore, there is an urgent need to develop a novel culture method for maintaining the stemness of adult stem cells.
Recently, Sun Chunhui of Jinan University and others have disclosed a polylactic acid-hydroxyapatite micro-nano multi-level structure composite microsphere material and its application. The material has good cell compatibility, can promote the proliferation of adult stem cells, the cell survival rate is over 98%, and can maintain the stemness of adult stem cells; the expanded adult stem cells have good differentiation potential and can differentiate into osteoblasts , fat and cartilage cells.
Wherein, the preparation method of polylactic acid-hydroxyapatite micro-nano multi-level structure composite microsphere material is as follows:
First, polylactic acid and CaCO3 are dispersed in dichloromethane to obtain a first solution, and microfluidic technology is used to drop the first solution into the polyvinyl alcohol aqueous solution to obtain uniform polylactic acid-CaCO3 microspheres.
The microspheres were then immersed in K2HPO4 solution, reacted with CaCO3 on the surface of the microspheres in a constant temperature water bath, washed with deionized water and absolute ethanol, and dried in vacuum to obtain polylactic acid composite microspheres coated with hydroxyapatite nanostructures. ball.
The microspheres are stable in structure, uniform in size, and have a diameter of 50-400 μm. Seeding human adipose-derived mesenchymal stem cells on the microspheres can promote the proliferation of stem cells and maintain the stemness of stem cells.
Epilogue
At present, China’s research on the application of calcium carbonate in biomedicine is gradually increasing, but the relatively mature application technology mainly focuses on drug release and primary API utilization, and the fruitful application scenarios cannot yet constitute a related system.