Engineering bone repair with K21-Infused brushite cement: In-vitro and in-vivo insights

Calcium phosphate biomaterials are widely used for bone regeneration, yet antibacterial and mechanical limitations persist. Brushite cements offer biodegradability and osteoconductivity but lack antimicrobial effects. Quaternary ammonium compounds (QACs), such as K21, provide potent antibacterial activity and tissue healing potential. This study developed and evaluated a novel K21-doped brushite cement with enhanced antibacterial and anti-inflammatory properties.

Brushite granules were synthesized from β-tricalcium phosphate and monocalcium phosphate monohydrate, followed by K21 drug loading (0.5 % and 1 % w/v). Material characterization used X-ray diffraction, Raman spectroscopy, and porosity analysis. In vitro tests included K21 release, antimicrobial efficacy against dual-species biofilms (P. aeruginosa, S. aureus), cytocompatibility with human gingival fibroblasts, and anti-inflammatory activity via protein denaturation assays. In vivo, mandibular critical-size defects were created in 24 rabbits (n = 8/group) and treated with control, 0.5 %, or 1 % K21-doped brushite cement. Bone regeneration and inflammatory response were assessed histologically at six weeks.

K21 incorporation showed pH-sensitive release with higher drug content at increased concentrations. Both 0.5 % and 1 % K21 cements significantly reduced microbial viability, with 1 % showing stronger bacteriostatic effects. All groups exhibited good cytocompatibility. In vivo, 0.5 % K21-doped cement achieved the greatest new bone formation (∼95 %) and reduced inflammation. In contrast, 1 % formulations induced increased inflammation despite antibacterial efficacy.

K21-doped brushite cements provide antibacterial, anti-inflammatory, and bone regenerative benefits. The 0.5 % formulation demonstrated optimal balance of safety and efficacy, making it a promising candidate for clinical use in craniofacial applications.

Bone graft failures are often linked to infection and inflammation. Incorporating K21 into brushite cement offers a dual-action material that not only supports bone regeneration but also reduces microbial risk and inflammatory complications, potentially improving outcomes in dental and maxillofacial defect repair.