ENHANCING OSSEOINTEGRATION OF BONE AND IMPLANTS THROUGH PHOTOCURRENT-DRIVEN IMMUNOREGULATION AND CALCIUM INFLUX ACTIVATION IN MACROPHAGES

The foreign body reaction is a complex physiological response critical for the integration of implanted materials, with macrophages playing an essential role in initiating acute inflammation and recruiting mesenchymal stem cells (MSCs) to promote regeneration. This pro-inflammatory response peaks within the first 24–48 hours post-implantation. However, failure of immune regulation can result in chronic inflammation, adversely affecting bone-to-implant integration in over 10% of cases. Therefore, it is crucial to restore the osteoimmune microenvironment promptly to prevent chronic inflammation and facilitate osseointegration. This can be achieved by inducing calcium influx in macrophages through photocurrent manipulation. This study utilized hydroxyapatite (HA), a biocompatible orthopedic material, to engineer an excitable surface via laser cladding on titanium substrates. The cladding process promoted the decomposition of HA, enhancing interaction with the titanium. Surface characterization was performed using X-ray diffraction, X-ray photoelectron spectroscopy, and electron spin resonance spectroscopy. The photocatalytic activity under 808 nm near-infrared (NIR) irradiation was evaluated through electrochemical measurements and hybrid density functional theory calculations. The impact of the photocurrent on modulating the osteoimmune microenvironment was assessed in both in vitro and in vivo settings to evaluate its efficacy in promoting osseointegration. The engineered surface formed a defective n-n heterojunction (CaTiO 3 -TiO 2 -Vo). Under NIR irradiation, this surface generated a photocurrent that effectively directed macrophage polarization, alleviating acute inflammation in the early post-implantation phase. Transcriptomic analysis and in vitro experiments indicated that photoelectric signals increased calcium influx into macrophages upon NIR exposure, altering the expression of calcium/calmodulin-dependent protein kinases, and inhibiting M1 macrophage polarization. This transformation fostered an osteoimmune microenvironment conducive to MSC recruitment and osteogenesis, accelerating osseointegration within 14 days of implantation. We have successfully engineered an excitable surface capable of remotely modulating the osteoimmune microenvironment to enhance osseointegration. Exposure to NIR irradiation generated a potent photocurrent that activated voltage-gated calcium channels, promoting a shift from M1 to M2 macrophage polarization. The resulting cytokine profile demonstrated a decrease in pro-inflammatory cytokines (TNF-α and iNOS) and an increase in anti-inflammatory cytokines (ARG-1 and IL-10). This strategic modulation significantly accelerated osseointegration in a tibial defect model, evidencing remarkable effectiveness as early as 14 days post-implantation.