High efficiency single-step biomaterial-based microparticle fabrication via template-directed supramolecular coordination chemistry

Biomaterial-based microparticles have attracted much attention for medical and biological applications such as pharmaceutics, bioseparation and cosmetics. Emerging technologies enable versatile and facile fabrication of microparticles, with key features being purity, precise size control, mild preparation conditions and minimal processing. Here, an innovative approach combining template synthesis, biomolecule assembly and partial-purification within a single step for high efficiency fabrication of pure biomaterial-based microparticles is reported. This concept is based on facile co-precipitation of biomolecules within CaCO₃ templates and simultaneous crosslinking of entrapped biomolecules via Ca²⁺ driven supra-molecular coordination chemistry, followed by template removal. Carbohydrate (alginate) and proteins (casein and fresh milk) are used as models of biomolecules. The process driven by selective crosslinking automatically excludes non-specific materials from the template and thus provides the additional function of partial-purification, as demonstrated using highly complexed fresh milk. This green approach to fabrication of biomaterial-based microparticles offers three critical advantages (i) mild conditions to preserve the chemical and secondary structures of biomolecules; (ii) single processing step to facilitate scale-up production; and (iii) partial-purification without the need for upstream raw material purification. This innovative approach not only addresses fundamental issues in fabrication techniques, but also marks progress in energy and environmental conservation during manufacturing processes.