Black Phosphorus Accelerates Bone Regeneration Based on Immunoregulation

Abstract

A fundamental understanding of inflammation and tissue healing suggests that the precise regulation of the inflammatory phase, both in terms of location and timing, is crucial for bone regeneration. However, achieving the activation of early inflammation without causing chronic inflammation while facilitating quick inflammation regression to promote bone regeneration continues to pose challenges. This study reveals that black phosphorus (BP) accelerates bone regeneration by building an osteogenic immunological microenvironment. BP amplifies the acute pro‐inflammatory response and promotes the secretion of anti‐inflammatory factors to accelerate inflammation regression and tissue regeneration. Mechanistically, BP creates an osteoimmune‐friendly microenvironment by stimulating macrophages to express interleukin 33 (IL‐33), amplifying the inflammatory response at an early stage, and promoting the regression of inflammation. In addition, BP‐mediated IL‐33 expression directly promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which further facilitates bone repair. To the knowledge, this is the first study to reveal the immunomodulatory potential of BP in bone regeneration through the regulation of both early‐stage inflammatory responses and later‐stage inflammation resolution, along with the associated molecular mechanisms. This discovery serves as a foundation for the clinical use of BP and is an efficient approach for managing the immune microenvironment during bone regeneration.

Phosphorus-Based Nanomaterials for Biomedical Applications: A Review

“…BLK-P enhances the acute pro-inflammatory response, stimulates the secretion of anti-inflammatory factors, and speeds up inflammatory regression and tissue regeneration. 165 Photo cross-linking gelatin, methacrylamide, BPNs, and cationic arginine-based unsaturated poly(ester amide) to prepare hydrogels retains BPN internally. Encapsulated BPN degrades to phosphorus ions and traps calcium ions, thereby accelerating biomineralization in skeletal defects.…”

“…Phosphorus-containing nanomaterials exhibit near-infrared responsiveness and have the ability to enhance the expression of heat shock proteins, thus facilitating tissue regeneration (Figure e). , Moreover, the presence of inorganic phosphate played a crucial role in the mineralization process, indicating that nanomaterials based on phosphorus can facilitate mineralization alongside degradation products . Phosphorus-based nanomaterials have the potential to generate a low ROS microenvironment, which may facilitate vascular recovery, nerve regeneration, calcium-dependent axon regeneration, and myelin formation .…”

“…This has generated significant interest in their biomedical applications. − BLK-P accelerates bone regeneration by creating an osteogenic immune microenvironment. BLK-P enhances the acute pro-inflammatory response, stimulates the secretion of anti-inflammatory factors, and speeds up inflammatory regression and tissue regeneration . Photo cross-linking gelatin, methacrylamide, BPNs, and cationic arginine-based unsaturated poly­(ester amide) to prepare hydrogels retains BPN internally.…”

Black phosphorus, an advanced versatile nanoparticles of antitumor, antibacterial and bone regeneration for OS therapy

“…Notably promising examples of 2D nanomaterial-based cancer therapeutics include BiOCl/Bi 2 O 3 NSs ( Chen et al, 2022a ), FeOCl/FeOOH NSs ( Kang et al, 2022 ), As/AsxOy NSs ( Kong et al, 2021 ). In recent years, BP nanoparticles has been used in a wide range of biomedical applications, such as bone tissue engineering ( Qiu et al, 2024 ), wound healing ( Bai et al, 2024 ), cancer therapy ( Wu et al, 2024a ), epilepsy treatment ( Yang et al, 2024 ), depression treatment ( Tan et al, 2024 ), spinal cord rehabilitation ( Liu et al, 2024 ), antibiotic treatment ( Wu et al, 2024b ). BP nanoparticles possess excellent biofouling and molecular loading capabilities for use in anticancer therapy.…”