The regeneration of damaged or lost tissue is considered to be a critical step toward realizing full organ regeneration in modern medicine. Although surgical techniques continue to advance, treatment for missing tissues in irregular wounds remains particularly difficult. With increasing interest in the application of additive manufacturing in tissue engineering, the fabrication of customized scaffolds for the regeneration of missing tissue via three-dimensional (3D) printing has become especially promising. Amongst the work on the regeneration of many important organs, liver regeneration is particularly interesting because liver diseases are increasingly prevalent in many countries around the world, resulting in a greater need for liver transplantation. The generation of hexagonal scaffolds for the regeneration of liver lobules is highly demanding, but their 3D structure has been proved difficult to reproduce by traditional fabrication methods. In this work, various hexagonal scaffolds are developed for liver lobule regeneration via 3D printing using novel biodegradable polymeric materials, including poly(glycerol sebacate) acrylate and poly(ethylene glycol) diacrylate. Through fine-tuning of printing parameters, a series of hexagonal scaffolds were designed and printed to mimic liver lobule units. The scaffolds were printed with various structures together with varying surface areas and 3D structures to enhance cell seeding density and diffusivity of the culture medium. Analysis of cell metabolic activities showed that the high-diffusion staircase (HDS) scaffold could support potential differences in cell proliferation rate. Furthermore, the HDS scaffolds composed of different copolymers were cultured with cells for up to 16 days to investigate the relationship between physical properties and hepatocyte proliferation. The results indicate that the combination of the high flexibility 3D printing with biodegradable, photocurable copolymers shows great promise for the regeneration of 3D liver lobules.

3D cell and organoid cultures, which allow in vitro studies of organogenesis and carcinogenesis, rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack rational design and control over key cell-instructive properties. Herein, we report a class of fully synthetic hydrogels based on novel DNA libraries that self-assemble with ultra-high molecular weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix). DyNAtrix enables, for the first time, computationally predictable, systematic, and independent control over critical viscoelasticity parameters by merely changing DNA sequence information without affecting the compositional features of the system. This approach enables: (1) thermodynamic and kinetic control over network formation; (2) adjustable heat-activation for the homogeneous embedding of mammalian cells; and (3) dynamic tuning of stress relaxation times over three orders of magnitude, recapitulating the mechanical characteristics of living tissues. DyNAtrix is self-healing, printable, exhibits high stability, cyto- and hemocompatibility, and controllable degradation. DyNAtrix-based 3D cultures of human mesenchymal stromal cells, pluripotent stem cells, canine kidney cysts, and human placental organoids exhibit high viability (on par or superior to reference matrices), proliferation, and morphogenesis over several days to weeks. DyNAtrix thus represents a programmable and versatile precision matrix, paving the way for advanced approaches to biomechanics, biophysics, and tissue engineering.

The induction of contact guidance in HIG-82 and HUVECs on laser-patterned biodegradable scaffolds.

We use DLP-AM to create a scaffold and culture cells on it to simulate fibrotic liver tissue.