Cell marbles: a novel cell encapsulation technology by wrapping cell suspension droplets using electrospun nanofibers for developmental engineering

Developmental Engineering aims to imitate natural tissue regeneration processes via an additive manufacturing approach. This research developes a technology to fabricate ready-made cell marbles (CMs) by wrapping cell suspension droplets of (3−15 μl) with electrospun hydrophobic nanofibers, as modular building blocks for developmental engineering. Human dermal fibroblasts and/or immortalised keratinocytes were suspended in the culture media cores of the CMs. The encapsulated cells were observed to precipitate at bottoms or up-inclined inner surfaces of the fibrous shells within 10 min. The CMs were mechanically strong enough to be handled as soft solids, thus easily and accurately delivered using forceps into three distinct culture systems, including tissue culture plastics, cellulosic scaffolds and in vitro fibrin wound models. The release of the cells, culture media and nanofibers into specific delivery points within the investigated culture systems was achieved via the controlled rupture of the CMs triggered by the simple hydrophobic-hydrophilic interaction between the nanofibers and the aqueous surroundings. Further cell and tissue culture studies indicated that the prominent traits of the skin cells were well preserved during cell encapsulation and delivery processes, suggesting the great potential of the CMs for additive tissue manufacturing in developmental engineering.