Functional Nanomaterials and 3D-Printable Nanocomposite Hydrogels for Enhanced Cell Proliferation and for the Reduction of Bacterial Biofilm Formation.

Biomaterial-associated infections are a major cause of biomaterial implant failure. To prevent the initial attachment of bacteria to the implant surface, researchers have investigated various surface modification methods. However, most of these approaches also prevent the attachment, spread, and growth of mammalian cells, resulting in tissue integration failure. Therefore, the success of biomaterial implants requires an optimal balance between tissue integration (cell adhesion to biomaterial implants) and inhibition of bacterial colonization. In this regard, we synthesize bifunctional nanomaterials by functionalizing the pores and outer surfaces of periodic mesoporous organosilica (PMO) with antibacterial tetracycline (Tet) and antibacterial and cell-adhesive bipolymer poly-d-lysine (PDL), respectively. Then, the fabricated TetPMO-PDL nanomaterials are incorporated into alginate-based hydrogels to create injectable and 3D-printable nanocomposite (NC) hydrogels (AlgL-TetPMO-PDL). These bifunctional nanomaterial and 3D-printable NC hydrogel show pH-dependent release of Tet over 7 days. They also enhance the proliferation of eukaryotic cells (fibroblasts). TetPMO-PDL is inactive in reducing Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis biofilms. However, AlgL-TetPMO-PDL shows significant antibiofilm activity against P. aeruginosa. These results suggest that the incorporation of TetPMO-PDL into AlgL may have a synergistic effect on the inhibition of the Gram-negative bacterial (P. aeruginosa) biofilm, while this has no effect on the reduction of the Gram-positive bacterial (S. aureus and E. faecalis) biofilm.