Repeatable Photodynamic Therapy with Triggered Signaling Pathways of Fibroblast Cell Proliferation and Differentiation To Promote Bacteria-Accompanied Wound Healing

Abstract

Despite the development of advanced antibacterial materials, bacterial infection is still a serious problem for wound healing because it usually induces severe complications and cannot be eradicated completely. Most current materials cannot simultaneously provide antibacterial activity, reusability, and biocompatibility as well as participate in stimulating cell behaviors to promote bacteria-accompanied wound healing. This work fabricated a hybrid hydrogel embedded with two-dimensional (2D) few-layer black phosphorus nanosheets (BPs) via simple electrostatic interaction. Within 10 min, 98.90% Escherichia coli and 99.51% Staphylococcus aureus can be killed rapidly by this hybrid, due to its powerful ability to produce singlet oxygen (O) under simulated visible light. In addition, this hydrogel also shows a high repeatability; that is, the antibacterial efficacy can still reach up to 95.6 and 94.58% against E. coli and S. aureus, respectively, even after challenging bacteria up to four times repeatedly. In vitro and in vivo results reveal that BPs in this hybrid hydrogel can promote the formation of the fibrinogen at the early stages during the tissue reconstruction process for accelerated incrustation. In addition, BPs can also trigger phosphoinositide 3-kinase (PI3K), phosphorylation of protein kinase B (Akt), and extracellular signal-regulated kinase (ERK1/2) signaling pathways for enhanced cellular proliferation and differentiation. Moreover, the hydrogel causes no appreciable abnormalities or damage to major organs (heart, liver, spleen, lung, and kidney) in rats during the wound healing process. Therefore, this BP-based hydrogel will have great potential as a safe multimodal therapeutic system for active wound healing and sterilization.

Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation

“…Moreover, the number of viable cells was higher on BP nanosheet‐functionalized DN gels than on the corresponding DN gels, suggesting that the BP nanosheets actively promote MC3T3 cell proliferation in our system. This is consistent with previous studies that have demonstrated that doping BP nanosheets caused a greater increase in cell proliferation compared to cells seeded on chitosan gels . We also observed a similar increase of ALP activity in MC3T3 cells grown of NE gels (Figure c) as for hBMSC.…”

Two‐Dimensional Materials for Antimicrobial Applications: Graphene Materials and Beyond

“…[223][224][225] However,B Pn anosheets as antibacterial agents have been seldom reported anda re still under explora-tion. [235][236][237] The currentp rogress indicates that BP nanosheets themselves are incapable of bacterial inactivation;h owever, the unique bandgape ndowst hem with outstanding photothermal/photodynamic performance, which is highly promising to combat bacterial infection.…”

“…Mao et al fabricated BP-embedded chitosan hydrogels (CS-BP) through electrostatic interactions to meet the requirements of satisfactory visible-light-driven photody- namic bactericidale fficiency and accelerated wound-healing performance. [236] Pure CS hydrogel showed intrinsic antibacterial activity (Figure20a) but was simultaneously toxic toward mammalian cells in the dark (Figure 20b) because of its positive charges. After the incorporation of BP,t he resultant CS-BP hydrogel became harmlesst od ermal fibroblasts in the dark (Figure 20b) due to partial neutralization of the positive charges.…”

Antibiotic‐Free Antibacterial Strategies Enabled by Nanomaterials: Progress and Perspectives

“…Recent research has focused on the development of nanomaterials with intrinsic photocatalytic activities, including graphene‐based materials, MoS 2 , black phosphorus nanosheets, and metal oxide nanomaterials to produce ROS under laser photoexcitation, acting as the PS for aPDT applications. The composition of nanomaterials is of great importance to regulate their PS efficacy.…”