Directed tissue self-assembly or bottom-up modular approach in tissue biofabrication is
an attractive and potentially superior alternative to a classic top-down solid scaffoldbased
approach in tissue engineering. For example, rapidly emerging organ printing
technology using self-assembling tissue spheroids as building blocks is enabling a
computer-aided robotic bioprinting of 3D tissue constructs. However, achieving proper
material properties while maintaining desirable geometry and shape of 3D bioprinted
tissue engineered constructs using directed tissue self-assembly, is still a challenge.
Proponents of directed tissue self-assembly see solution of this problem in developing
methods of accelerated tissue maturation and/or using sacrificial temporal supporting of
removable hydrogels. In the meantime, there is a growing consensus that a third strategy
based on the integration of a directed tissue self-assembly approach with a conventional
solid scaffold-based approach could be a potential optimal solution. We hypothesize that
tissue spheroids with “velcro®-like” interlockable solid microscaffolds or simply
“lockyballs” could enable the rapid in vivo biofabrication of 3D tissue constructs at
desirable material properties and high initial cell density. Recently, biocompatible and
biodegradable photo-sensitive biomaterials could be fabricated at nanoscale resolution
using two-photon polymerization (2PP), a development rendering this technique a high
potential to fabricate “velcro-like” interlockable microscaffolds. Here we report design
studies, physical prototyping using 2PP and initial functional characterization of interlockable
solid microscaffolds or so-called “lockyballs”. 2PP was used as a novel enabling
platform technology for rapid bottom-up modular tissue biofabrication of interlockable
constructs. The principle of lockable tissue spheroids fabricated using the described
lockyballs as solid microscaffolds is characterized by attractive new functionalities such
as lockability and tunable material properties of the engineered constructs. It is
reasonable to predict that these building blocks create the basis for a development of a
clinical in vivo rapid biofabrication approach and forms part of recent promising
emerging bioprinting technologies