Arbitrarily-shaped microgels composed of chemically unmodified biopolymers

Biohydrogels, composed of naturally occurring biopolymers are typically preferred over their synthetic analogues in bioapplications thanks to their biocompatibility, bioactivity, mechanical or degradation properties. Shaping biohydrogels on the single-cell length scales (micrometers) is a key ability needed to create bioequivalent artificial cell/tissue constructs and cannot be achieved with current methods. This work introduces a method for photolithographic synthesis of arbitrarily shaped microgels composed purely of a biopolymer of choice. The biopolymer is mixed with a sacrificial photocrosslinkable polymer, and the mixture is photocrosslinked in a lithographic process, yielding anisotropic microgels with the biopolymer entrapped in the network. Subsequent ionic or covalent biopolymer crosslinking followed by template cleavage yields a microgel composed purely of a biopolymer with the 3D shape dictated by the photocrosslinking process. Method feasibility is demonstrated with two model polysaccharide biopolymers (alginate, chitosan) using suitable crosslinking methods. Next, alginate microgels were used as microtaggants on a pharmaceutical oral solid dose formulation to prevent its counterfeiting. Since the alginate is approved as an additive in the food and pharmaceutical industries, the presented tagging system can be implemented in practical use much easier than systems comprising synthetic polymers.