Multifunctional ADA-GEL hydrogels reinforced with iron-loaded dendritic bioactive glass nanoparticles for bone regeneration

Introduction: Bone-related diseases and injuries, including osteoporosis, osteomyelitis, and fractures, affect millions globally and pose increasing challenges to public health due to the aging population [1], [2]. Hydrogels composed of natural polymers, particularly when reinforced with bioactive glasses, have gained attention for their tunable mechanical properties, biocompatibility, and ability to support osteogenesis and angiogenesis [3]. In this context, we developed iron-loaded dendritic mesoporous bioactive glass nanoparticles incorporated into alginate-di-aldehyde–gelatin (ADA-GEL) hydrogels, evaluating their physicochemical properties and biological performance.

Materials and methods: Dendritic mesoporous bioactive glass nanoparticles (DMBGNs) were synthesized by first preparing dendritic mesoporous silica nanoparticles (DMSNs) using a dual surfactant template method in a solvent-free system [4]. Calcium and iron were incorporated by dispersing DMSNs in an ethanolic solution of calcium nitrate and iron nitrate, respectively. ADA-GEL hydrogels were prepared following the protocol established at the FAU Institute of Biomaterials [5]. Briefly, 5% oxidized alginate and 7.5% gelatin were mixed in DPBS. Next, 0.1% DMBGNs were incorporated into ADA prior to gelatin addition, and printability was assessed using a BioScaffolder printer, printing a 4-layer scaffolds.

Results: Dendritic mesoporous bioactive glass nanoparticles were synthesized by loading different concentrations of Ca²⁺ and Fe³⁺, resulting in flower-like porous structures and high surface areas. When incorporated into ADA-GEL hydrogels, nanoparticles maintained their bioactivity, supported by apatite formation in SBF. FTIR and XRD confirmed crosslinking and structural integration, while SEM revealed porous, interconnected hydrogel morphology. Degradation and mechanical tests highlighted improved structural stability in Fe-containing hydrogels, with good printability and mechanical properties.

Conclusions: The results demonstrate that Fe-loaded DMBGNs can be effectively synthesized and integrated into ADA-GEL hydrogels, preserving their mesoporous structure and enhancing mechanical properties, printability, and bioactivity. These findings highlight the potential of ion-modified dendritic bioactive glass nanoparticle containing hydrogels as multifunctional bioinks for regenerative medicine.