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Abstract
There is a need for a model to better mimic human physiology in the clinic, so the objective was to develop a novel bioink for a 3D tissue model to study human disease and development in a dynamic 3D environment. The results from each corresponding study helped in developing a novel bioink for use in a bioprinted human vascularized organoid. The bioink composed of alginate with other natural hydrogels to function as extracellular matrix and with the addition of borophosphate bioactive glasses (BPBGs) to replace growth factors, can be used with multiple cell types to bioprint the proposed organoid.
Bioactive glass with varying borate-to-phosphate can be added to release therapeutic ions to support multiple types of cells without significantly altering the local pH in vivo and in vitro. First, the biological effects of these BPBGs were investigated by multiple assays in vitro and in vivo. The results conclude that the pH neutral BPBGs supported endothelial cell proliferation and migration in cell culture and had greater blood vessel formation in the in vivo model, while BPBGs can directly influence viability, differentiation, and migration in adipose stem cells (ASCs) and their secretome. Next, BPBGs were used in an alginate-gelatin hydrogel bioink with ASCs in bioprinted scaffolds. This resulted in the creation of a bioink in which the BPBGs release desired ionic species that stimulate desired cellular responses and can control the bioink viscosity for optimized printing of scaffolds. Finally, a novel bioink made via inner gelation with fibrin instead of gelatin to create a more human-like bioink for the fabrication of a vascularized organoid. Eventually, the organoid can be included in a microphysiological system to facilitate studying developmental biology and disease mechanisms.
