Injectable Mineralized Nanocomposite Hydrogels for Antibacterial and Reconstructive Treatment of Bone Infections

Bone infections and critical defects pose substantial challenges in orthopaedic treatment, driven by their complexity and the limited effectiveness of current therapeutic approaches in clinical practice. To address this, multifunctional injectable nanocomposite hydrogels incorporating strontium-substituted hydroxyapatite nanoparticles (Sr-HAp) within a covalently cross-linked ɛ-polylysine (ɛ-PL) and hyaluronic acid (HA) hydrogel network were developed. These mineralized hydrogels aim to combine the osteogenic and bioactive properties of Sr-HAp nanoparticles with the inherent antibacterial activity of ɛ-PL-HA hydrogels, offering a dual-functional approach for bone reconstruction. The physical and biological properties of the hydrogels were extensively characterized. Rheological assessments confirmed their viscoelastic behaviour and injectability, which are critical for minimally invasive applications. Structural properties were optimized by varying Sr-HAp content, resulting in mineralized hydrogels with tunable performance. Enzymatic degradation studies demonstrated excellent stability, with degradation timeframes extending from 5 to 19 weeks as Sr-HAp content increased from 40% to 60%. Despite the high nanoparticle loading, the hydrogels retained their fast-acting and long-term antibacterial efficacy against E. coli and S. aureus (ATCC bacterial strains), as well as clinically isolated multidrug-resistant ESBL E. coli and MRSA bacterial strains. In vitro biocompatibility studies highlighted the ability of the mineralized hydrogels to support cell proliferation and promote pre-collagen I synthesis, underscoring their potential for bone tissue engineering. The sustained release of Sr 2+ ions further enhanced osteogenic activity by activating critical signaling pathways, facilitating bone regeneration. This work demonstrates the potential of Sr-HAp/ɛ-PL-HA nanocomposite hydrogels as injectable, multifunctional biomaterials with synergistic functionalities for the antibacterial and reconstructive treatment of bone infections. The authors acknowledge financial support from the European Union's Horizon 2020 research and innovation programme under the grant agreement No. 857287.