When an implant is introduced into the body, it triggers a complex immune response known as the foreign body reaction (FBR). This process involves various cellular and molecular events that influence the integration of the implant with the surrounding bone. Macrophages are among the first immune cells to respond to the implant, playing a key role in the FBR by activating an acute inflammatory response. This reaction involves the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-????), which helps recruit mesenchymal stem cells (MSCs) to begin the bone regeneration process. The inflammatory response begins immediately after implantation and peaks within the first few days. However, if the immune system's self-regulation is impaired due to a local pathological condition, the inflammation may not subside in time, potentially leading to chronic inflammation. This prolonged inflammation can result in several complications, including fibrous capsule formation, bone resorption, implant degradation, or delays in integration, all of which may contribute to implant failure. In fact, more than 10% of implant failures are linked to loosening. Therefore, it is crucial to restore balance between the bone and implant after the initial inflammation phase to prevent long-term complications and ensure successful integration.

To address this, a team of researchers from the LKS Faculty of Medicine at the University of Hong Kong (HKUMed, Hong Kong SAR, China) has developed a groundbreaking photocurrent-responsive implant surface designed to speed up bone-to-implant integration following orthopedic surgery. This advanced surface coating has been shown to reduce the integration time to just two weeks, significantly enhancing post-operative recovery and reducing the risk of rejection. The team is currently exploring the application of this technology in artificial joint replacement surgeries, such as knee replacements. Disruptions to the osteoimmune microenvironment during the post-implantation phase can lead to implant loosening, extended recovery times, and increased complications, ultimately resulting in failure.

To address these issues, the HKUMed team created an implant surface that responds to near-infrared (NIR) light, which modulates the macrophage response and helps control inflammation in the crucial early stages after implantation. The surface generates a photocurrent when exposed to NIR light, causing increased calcium influx in macrophages, which fosters a more favorable osteoimmune environment. This, in turn, accelerates the recruitment of MSCs and promotes bone formation, thereby speeding up the bone-to-implant integration process. While traditional orthopedic implants are often coated with titanium dioxide (TiO2) due to its non-toxicity to bone cells and bacteria, it lacks responsiveness to NIR. NIR light, known for its ability to penetrate biological tissues, is commonly used in treatments for infections and cancer.

In this study, the researchers used hydroxyapatite (HA), the primary mineral in bones and teeth, to create a responsive implant surface. This innovative coating generates photoelectric signals when exposed to NIR light, which helps reduce inflammation and regulate macrophage differentiation, thus creating a conducive immune environment for bone-to-implant integration. The regulation of immune cells further enhances the recruitment of MSCs for bone formation, accelerating the integration process and improving the stability of the implant. In experiments with a tibial defect animal model, the researchers demonstrated that bone-to-implant integration was accelerated from 28 days to just 14 days, effectively doubling the speed. This marks the first study to use a photocurrent to non-invasively regulate immune cells, offering promising potential for the development of new biomaterials that can remotely control the local immune environment.

“Our team has successfully developed an engineered surface that non-invasively modulates macrophage differentiation according to the patient's immune cycle and needs,” said Professor Kelvin Yeung Wai-kwok, who led the research. “Animal experiments have proved that this method significantly accelerates bone-to-implant integration, resulting in a twofold increase in the fusion rate. We aim to expand the application of this engineered surface in orthopedic surgeries in future research to enhance patient recovery. This discovery has a profound impact on the success rate of orthopedic surgery and provides a new direction for addressing clinical challenges, like implant rejection. 

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