Dynamically Crosslinked Gold Nanoparticle – Hyaluronan Hydrogels

Bioprinting employs three-dimensional (3D) deposition of cells and biomaterials to create organized structures with organappropriate architecture. Such engineered organs could offer alternatives to inadequate donor organ supplies, [ 1 , 2 ] and bioprinted human tissues could improve predictability during preclinical evaluation of therapeutic agents. [ 3 ] However, scalability of bioprinting is limited by lack of extrudable, biocompatible materials that can retain form, be remodeled by cells, be removed to create lumens, and offer layer-to-layer connectivity following assembly. To address these needs, we developed dynamically crosslinkable materials using gold nanoparticles (AuNPs) as multivalent crosslinkers. Specifi cally, 24 nm AuNPs and thiolmodifi ed biomacromonomers derived from hyaluronic acid (HA) and gelatin were used to form printable semi-synthetic extracellular matrix (sECM) hydrogels. AuNP-sECMs are unique in having dynamic crosslinks; that is, both intra-gel and inter-gel covalent interactions can form and reform during and after printing. Moreover, AuNP-thiol crosslinking is reversible in the presence of benign thiols such as cysteine. In a proof-ofconcept experiment, AuNP-sECMs were used to print tubular tissue constructs using an automated bioprinting system. In bioprinting, cells (the “bio-ink”) and hydrogels (the “biopaper”) are deposited into precise 3D geometries by a 3-axis printer in a fashion enabling maturation into functional tissues. [ 4,5 ] Recently, cell aggregates and cell rods were printed into tubular assemblies that fused into seamless structures. [ 6,7 ]