Biomimetic Microcarriers for Cell Storage and Transportation under Ambient Temperature Applied on Regenerative Medicinal Products Development

Cell therapy has received considerable attention in the field of tissue engineering. Proper cell culture systems have been an indispensable tool from bench to bed. Spherical microcarriers have been developed for many years, but the poor nutrient permeability makes their disadvantages in long-term cultivation. And after cell expansion in laboratory, efficient and safe transport methods are extremely important issue. Frozen cell shipping methods have been used for decades. However, from storage to delivery, the cost is high, the procedure is dangerous, and the cryoprotectant is cytotoxic at ambient temperature. It is not appropriate to apply on long-term shipping or air transportation. Undoubtedly, a simple, cheap and harmless cell storage and transportation method are expected in clinical. The aim of this project is to develop a biomimetic microcarrier with nanoporous structure on the surface. The nanopores will be fabricated through a self- designed microfluidic system, and the uncross-linked gelatin after high- temperature sterilized treatment will play as the core inside. The strategy can combine with three-dimensional dynamic cell culture system. In the first year, we will develop cell microcarriers with nanoporous structure on the surface, evaluate the long-term cell culture effect, and compare the advantages of nanopores. Move on to the second year, we will use uncrosslinked sterilized gelatin as the core element to explore the protective ability of RGD sequence to cells and its mechanism during transportion at ambient temperature. Finally, in the third year, the practicability of biomimetic microcarriers will be further confirmed via carrying adipose-derived stem cells (ADSCs) and promoting the differentiation of ADSCs toward osteogenesis for bone regeneration. The biomimetic microcarriers developed in this projects have a shell-core structure, which can provide a favorable microenvironment not only for cell storage and transpotation under ambient temperature, but also for cell ingrowth at 37°C.