3D Assembly of Cryo(Bio)Printed Modular Units for Shelf-Ready Scalable Tissue Fabrication

The human body relies on modular assembly for realizing its functions. Here the development of a bioinspired cryo(bio)printing-based method is reported to fabricate shelf-ready, storable modular scaffolds toward scalable tissue assembly. The mechanism lies in that the cryo(bio)printed modular scaffolds are first assembled into the final hierarchy in their frozen state, which can be subsequently bonded together into an integral piece by contacting each other at the interface during the melting and photocrosslinking processes. This method not only addresses the height limitation associated with the recently developed cryo(bio)printing technology by enabling scalable tissue fabrication through modular assembly, but also allows generating tissue constructs of same or dissimilar materials to fit defects of different scales and shapes, thus providing more precision treatment. Cellular evaluations on the cryobioprinted modular hydrogels validate cell viability, spreading, and differentiation following assembly. The chick ex ovo and rat subcutaneous implantation assays further confirm the potential of direct in vivo assembly using shelf-ready cryobioprinted modular tissue constructs. A cryo(bio)printing-based method to fabricate shelf-ready, storable modules toward scalable tissue assembly is developed, where cryo(bio)printed modular scaffolds are first assembled into the final hierarchy in frozen state, which are subsequently bonded together into an integral piece during the melting and photocrosslinking processes, addressing the height limitation associated with cryo(bio)printing, and allowing generating tissue constructs of same or dissimilar materials.image