Development of β-TCP based Antimicrobial Injectable Bone Grafts

Beta-tricalcium phosphate (β-TCP) is a widely utilized biomaterial in bone grafts due to its osteoinductivity, biocompatibility, and biodegradability. Especially, injectable bone grafts that can be locally applied with a special syringe to irregularly shaped bone defect areas may be advantageous. However, its low mechanical strength limits its effectiveness in load-bearing applications. To overcome this problem, the usage of sintered β-TCP, may provide enhanced mechanical strength to the injectable bone grafts since sintering process increases the mechanical strength of β-TCP and improves its structural stability. Although most of the current strategies for bone regeneration provide relatively satisfactory results, the lack of antimicrobial efficacy in bone grafts limits their use. Current clinical treatment strategies usually involve antibiotic therapy with broad-spectrum antibiotics, following extensive surgical debridement. However, these antibiotics cause bacterial resistance and systemic side effects. Antimicrobial peptides (AMPs) are promising antibacterial agents due to their broad-spectrum antibacterial activity, controllable biocompatibility and limited resistance development. KR-12, a cationic AMP derived from human LL-37, shows strong antibacterial activity, low toxicity and promotes osteogenic differentiation in mesenchymal stem cells, making it a promising candidate for topical application in the management of infections. In this study, we designed an injectable bone graft by combining sintered and unsintered β-TCP in various ratios to enhance the mechanical strength of the grafts. To address the lack of antimicrobial efficacy, we functionalized the grafts with the antimicrobial peptide KR-12, known for its broad-spectrum antibacterial activity and low resistance development. The optimal peptide concentration was determined, creating a graft with both improved mechanical strength and effective antibacterial properties. Future studies will assess its antimicrobial effectiveness and impact on osteogenic differentiation using mesenchymal stem cells.