Interfacial delivery of carbon monoxide via smart titanium implant coating for enhanced soft tissue integration with switchable antibacterial and immunomodulatory properties

Abstract

Soft tissue integration around titanium (Ti) implants is weaker than that around natural teeth, compromising long-term success of Ti implants. Carbon monoxide (CO) possesses distinctive therapeutic properties, rendering it as a highly promising candidate for enhancing STI. However, achieving controlled CO generation at the STI interface remains challenging. Herein, a controlled CO-releasing dual-function coating was constructed on Ti surfaces. Under near-infrared (NIR) irradiation, the designed surface could actively accelerate CO generation for antibiosis against both aerobic and anaerobic bacteria. More importantly, in the absence of NIR, the slow release of CO induces macrophage polarization from pro-inflammatory phenotype towards pro-regenerative phenotype. In a rat implantation model with induced infection, the designed surface effectively controlled the bacterial infection, alleviates accompanying inflammation and modulated immune microenvironment, leading to enhanced STI. Single-cell sequencing revealed that the coating alters the cytokine profile within the soft tissue, thereby influencing cellular functions. Differentially expressed genes in macrophages are highly enriched in the PIK3-Akt pathway. Furthermore, the cellular communication between fibroblasts and macrophages was significantly enhanced through the CXCL12/CXCL14/CXCR4 and CSF1-CSF1R ligand-receptor pair. These findings indicate that our coating showed an appealing prospect for enhancing STI around Ti implants, which would ultimately contribute to the improved long-term success of Ti implants.

Graphical abstract

Titanium (Ti) implants exhibit weaker soft tissue integration (STI) compared to natural teeth, affecting their long-term success. Carbon monoxide (CO), known for its therapeutic properties, emerges as a promising candidate for improving STI.However, controlled CO delivery at the STI interface poses a challenge. This study introduces a dual-function, controlled CO-releasing coating on Ti implants. Upon near-infrared (NIR) irradiation, this coating boosts CO generation for antibiosis. Crucially, without NIR, it gradually releases CO, shifting macrophages from a pro-inflammatory to a pro-regenerative phenotype. In a rat maxillary implant model, this innovative surface managed bacterial infection, reduced inflammation, and modulated the immune microenvironment, thereby enhancing STI.

Highlights

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  A peptidomimetic functional coating on titanium surfaces with abundant catechols and thiol groups was developed.

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  The coating is capable of achieving controlled local release of CO in response to NIR irradiation.

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  The coating improved peri-implants soft tissue integration through antibacterial and immunomodulatory properties.