Smart Design for Hybrid Bioprinting of Scalable and Viable Tissue Constructs

Hybrid bioprinting uses sequential printing of melt-extruded biodegradable thermoplastic polymer and cell-encapsulated bioink in a predesigned manner using high- and low-temperature print heads for the fabrication of robust three-dimensional (3D) biological constructs. However, the high-temperature print head and melt-extruded polymer cause irreversible thermal damage to the bioprinted cells, and it affects viability and functionality of 3D bioprinted biological constructs. Thus, there is an urgent need to develop innovative approaches to protect the bioprinted cells, coming into contact or at close proximities to the melt-extruded thermoplastic polymer and the high-temperature print head during hybrid bioprinting. Therefore, this study investigated the potential of iterating the structural architecture pattern (SAP) of melt-printed thermoplastic layers and the cell printing pattern (CPP) to protect the cells from temperature-associated damage during hybrid bioprinting. A novel SAP for printing the thermoplastic polymer and an associated CPP for minimizing thermal damage to the 3D bioprinted construct have been developed. The newly developed SAP- and CPP-based hybrid bioprinted biological constructs showed significantly low thermal damage compared to conventionally hybrid bioprinted biological constructs. The results from this study suggest that the newly developed SAP and CPP can be an improved hybrid bioprinting strategy for developing living constructs at the human scale. Impact statementThe study introduces a novel approach to address the viability loss associated with thermal damage in hybrid bioprinted biological constructs. Combining a unique structural architecture design for the thermoplastic component and a specialized cell printing pattern for the bioink component has been shown to overcome the viability loss associated with thermal damage in hybrid bioprinted tissue constructs. This solution has broad implications for biofabricating viable engineered tissues and model systems for in vitro studies and enables the fabrication of human-scale engineered tissues for regenerative medicine. The findings demonstrated in this study can propel bioprinting innovations, impacting biomedical research and health care.