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Early osteoimmune microenvironment disorder at the interface between bone and implant can lead to implant loosening, which prolongs patient convalescence, exacerbates postoperative complications, and potentially results in implant failure. The timely regulation of macrophages primarily orchestrates the entire long‐term regeneration process. Here, it is proposed to precisely direct macrophage polarization using localized photoelectrical signals generated by an excitable surface in response to remote stimulation via near‐infrared light (NIR). The photocurrent generated from the n–n heterojunction between calcium titanate (CaTiO3) and defective titanium dioxide (TiO2‐Vo) on the excitable surface can accurately direct macrophage polarization, suppressing acute inflammation at the early stage of post‐implantation and establishing a favorable osteoimmune microenvironment that promotes bone‐to‐implant integration. Mechanistic study reveals that photoelectric signals initiate increased calcium influx via voltage‐gated calcium ion channels, subsequently modulating calcium/calmodulin‐dependent protein kinase kinase 2 (Camkk2) and calcium/calmodulin‐dependent protein kinase I (Camk1) expression to regulate macrophage polarization. This optimization of the osteoimmune microenvironment results in enhanced mesenchymal stem cells (MSCs) recruitment and osteogenesis, ultimately accelerating bone‐to‐implant integration within 14 days post‐implantation. This research presents a novel method for adjusting in vivo spatiotemporal immune responses through the use of noninvasive and externally‐controlled targeted stimulations. [ABSTRACT FROM AUTHOR]

Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu. Excessive bone marrow adipocytes accumulation is involved in bone deterioration. Here, the authors show that adipocyte ESRRA abrogation promotes osteogenesis and vascular formation in adipocyte-rich bone marrow via oppositely regulating the expression and secretion of leptin and SPP1. [ABSTRACT FROM AUTHOR]

Achieving bacterial killing and osteogenic formation on an implant surface rarely occurs. In this study, a novel surface design-a palladium hydride (PdH x ) film that enables these two distinct features to coexist is introduced. The PdH x lattice captures protons in the extracellular microenvironment of bacteria, disrupting their normal metabolic activities, such as ATP synthesis, nutrient co-transport, and oxidative stress. This disruption leads to significant bacterial death, as evidenced by RNA sequence analysis. Additionally, the unique enzymatic activity and hydrogen-loading properties of PdH x activate the human antioxidant system, resulting in the rapid clearance of reactive oxygen species. This process reshapes the osteogenic immune microenvironment, promoting accelerated osteogenesis. These findings reveal that the downregulation of the NOD-like receptor signaling pathway is critical for activating immune cells toward M2 phenotype polarization. This novel surface design provides new strategies for modifying implant coatings to simultaneously prevent bacterial infection, reduce inflammation, and enhance tissue regeneration, making it a noteworthy contribution to the field of advanced materials., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivo show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials., Competing Interests: Kelvin W. K. Yeung is an associate editor for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. Xuanyong Liu is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)