3D-printed magnesium/nanodiamond dual-doped hydroxyapatite composite hydrogels with antibacterial and in vitro bioactive properties for bone tissue engineering

Abstract

Bone regeneration remains a critical challenge in personalized healthcare, particularly when combating bacterial infections that impede healing. While various scaffold systems have been developed, the combination of magnesium and nanodiamond dual-doped hydroxyapatite (MgND-HAp) with natural polymers in a 3D-printable format, offering both antimicrobial protection and enhanced cellular response, has not been previously explored. In this study, we developed 3D-printable hydrogel scaffolds combining carboxymethyl chitosan, gelatin, and MgND-HAp for bone tissue engineering applications. The carboxymethyl chitosan–gelatin (CMG) hydrogel scaffolds were comprehensively evaluated for structural, physicochemical, and biological characteristics. x-Ray diffraction confirmed successful MgND-HAp incorporation, while rheological studies showed improved printability with increasing MgND-HAp concentration. The CMG 4% formulation exhibited optimal viscoelastic behavior (elastic modulus ∼12.5 kPa) and toughness (2.1 MJ/m³) with increasing concentration of MgND-HAp. Biocompatibility studies revealed enhanced cell viability and migration of human mesenchymal stem cells compared to control scaffolds. The increasing concentration of MgND-HAp demonstrated remarkable antibacterial efficacy against Escherichia coli (90%) and methicillin-resistant Staphylococcus aureus (95%) bacteria. Crystal violet staining assays confirmed significant biofilm inhibition across all MgND-HAp-containing formulations. These findings suggest that the developed CMG hydrogel scaffolds, particularly the CMG 2% and CMG 4% formulations, offer a promising platform combining excellent printability, mechanical stability, biocompatibility, and antimicrobial properties for bone tissue engineering applications.