Cellular bioink surface tension: A tunable biophysical parameter for faster maturation of bioprinted tissue

Bioprinting provides an exceptional platform for tissue engineers to deposit cells onto substrates with precision, and to construct three-dimensional (3D) biological structures such as tissues and organs. In extrusion bioprinting of cells, cellular bioink particles in the form of multicellular systems are printed on supportive materials such as agarose. Post-printing and before implantation, the 3D biological structure undergoes a complex maturation process governed by both biological and physical mechanisms. Controlling the maturation time to expedite the regeneration of human tissues remains challenging. Herein, we provide evidence that the fusion of cellular bioink (a critical step in tissue maturation) can be accelerated by higher apparent tissue surface tension (ATST) of the cellular bioink particles. Two different preparation methods, namely the egg holder aggregate maker and cylindrical aggregate fabrication, were used to fabricate cellular bioink of Chinese hamster ovary (CHO) and human skin fibroblast (HSF) cells. Each method produced distinct ATSTs from aggregates of the same cell type. The characteristic fusion times for CHO aggregates with 14.71 dyne/cm and 22.8 dyne/cm were found 181.95 h and 93.15 h respectively. The same trend was observed for HSF as aggregates with a higher surface tension fused faster. Therefore, controlling tissue fusion can be achieved through adjusting the ATST of bioprinted spheroids via our fabrication method. This is an essential initial step towards engineering tissues of defined anatomical and histological structures.