Two-Dimensional Biodegradable Black Phosphorus Nanosheets Promote Large Full-Thickness Wound Healing through In Situ Regeneration Therapy

Abstract

Large full-thickness skin lesions have been one of the most challenging clinical problems in plastic surgery repair and reconstruction. To achieve in situ skin regeneration and perfect clinical outcomes, we must address two significant obstacles: angiogenesis deficiency and inflammatory dysfunction. Recently, black phosphorus has shown great promise in wound healing. However, few studies have explored the bioeffects of BP to promote in situ skin regeneration based on its nanoproperties. Here, to investigate whether black phosphorus nanosheets have positive bio-effects on in situ skin repair, we verified black phosphorus nanosheets' positive effects on angiogenic and anti-inflammatory abilities in vitro. Next, the in vivo evaluation performed on the rat large full-thickness excisional wound splinting model more comprehensively showed that the positive bio-effects of black phosphorus nanosheets are multilevel in wound healing, which can effectively enhance anti-inflammatory ability, angiogenesis, collagen deposition, and skin re-epithelialization. Then, multiomics analysis was performed to explore further the mechanism of black phosphorus nanosheets' regulation of endothelial cells in depth. Molecular mechanistically, black phosphorus nanosheets activated the JAK-STAT-OAS signaling pathway to promote cellular function and mitochondrial energy metabolism in endothelial cells. This study can provide a theoretical basis for applying twodimensional black phosphorus nanosheets as nanomedicine to achieve in situ tissue regeneration in complex human pathological microenvironments, guiding the subsequent optimization of black phosphorus.

Black Phosphorus-Based Dynamic Self-Healing Hydrogel to Integrate Demineralized Bone Matrix and Noggin-Targeting siRNA for Synergistic Osteogenesis

“…Numerous nanomaterials have been explored for biomedical applications, such as drug delivery, tissue regeneration, biosensing, and diagnosis. − Black phosphorus (BP), a 2D nanomaterial, has attracted the attention of researchers from a wide range of fields due to its distinctive atomic structure arrangement and remarkable physical-optical properties. − BP has demonstrated its significant application potential in biomedical fields, particularly in cancer therapy, bioimaging, and drug delivery, benefiting from its inherent biocompatibility, large specific surface area, and exceptional near-infrared light photothermal/photoelectric conversion efficiency. − BP is a promising gene delivery vehicle since it can spontaneously degrade in response to the intracellular microenvironment. , Most significantly, the degradation products of BP are phosphate/phosphite, which can spontaneously combine with Ca 2+ to form CaP nanoparticles in the physiological environment, leading to in situ biomineralization . Given this unique property, BP has been used in various bone conduction materials.…”

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.…”