MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.

Emerging treatments for corneal endothelium decompensation - a systematic review.

PURPOSE: Endothelial keratoplasty (EK) is the conventional treatment to improve visual acuity of corneal endothelium decompensation (CED) patients, with other therapies mainly for symptomatic relief. However, the shortage of corneal grafts and other limitations to EK urge the development of novel alternative treatments. In the last decade, novel options have been proposed, yet only a limited number of reviews have systematically reported on outcomes. Therefore, this systematic review evaluates the existing clinical evidence of novel surgical approaches for CED. METHOD: We identified 24 studies that illustrated the clinical observations of the surgical approaches in interest. We included Descemet stripping only (DSO), Descemet membrane transplantation (DMT) where Descement membrane alone instead of corneal endothelium with cells is transplanted, and cell-based therapy. RESULTS: In general, these therapies may provide visual outcomes comparable with EK under specific conditions. DSO and DMT target CED with relatively healthy peripheral corneal endothelium like Fuchs' corneal endothelial dystrophy, while cell-based therapy offers more versatile applications. Side effects of DSO would decrease with modifications to surgical techniques. Moreover, Rho-associated protein kinase inhibitor adjuvant therapy could enhance clinical results in DSO and cell-based therapy. CONCLUSION: Long-term controlled clinical trials with larger sample size on the therapies are needed. The simplicity of DSO and the high translational potential of cell-based therapy to treat CED of most etiologies made these two treatment strategies promising.

Bioactive Glial-Derived Neurotrophic Factor from a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors from Retinal Degeneration in Rabbits.

The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen-alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial-cell-line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases. This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium-iodate (SI)-induced retinal degeneration. The findings indicated that the CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants.

Photo-Activated Nanofibrous Membrane with Self-Rechargeable Antibacterial Function for Stubborn Infected Cutaneous Regeneration.

For quick disinfection treatment, phototherapy, including photothermal therapy and photodynamic therapy, has emerged as a promising alternative to conventional methods. However, the bactericidal effect of phototherapy, which only works upon light, is short-lived. The remaining bacteria in situ may repopulate when the irradiation of light is withdrawn. To address this refractory concern, an antibacterial fibrous membrane consisting of electrospun poly (polycaprolactone) scaffolds and polydopamine (pDA) coated MXene/Ag3 PO4 bioheterojunctions (MX@AgP bio-HJs) is devised and developed. Upon near-infrared (NIR) illumination, the MX@AgP nanoparticle (NP) in nanofibrous electrospun membranes exert the excellent bactericidal effect of phototherapy and release Ag+ ions which stop the remaining bacteria from multiplying in the dark state. When removing NIR light, pDA in situ reduces Ag+ ions to Ag0 NPs to realize the self-rechargeability of Ag+ ions and provides enough Ag+ ions for the second phototherapy. In vivo results show that photoactivated nanofibrous membranes can re-shape an infected wound microenvironment to the regenerative microenvironment through killing bacteria, ceasing bleeding, increasing epithelialization, and collagen deposition on the wound bed, as well as promoting angiogenesis. As predicted, the proposal work offers potential prospects for nanofibrous membranes with NIR-assisted "self-rechargeable" antibacterial properties to treat bacteria-infected full-thickness wounds.

A systematic review of multimodal clinical biomarkers in the management of thyroid eye disease.

Thyroid Eye Disease (TED) is an autoimmune disease that affects the extraocular muscles and periorbital fat. It most commonly occurs with Graves' Disease (GD) as an extrathyroidal manifestation, hence, it is also sometimes used interchangeably with Graves' Ophthalmopathy (GO). Well-known autoimmune markers for GD include thyroid stimulating hormone (TSH) receptor antibodies (TSH-R-Ab) which contribute to hyperthyroidism and ocular signs. Currently, apart from radiological investigations, detection of TED is based on clinical signs and symptoms which is largely subjective, with no established biomarkers which could differentiate TED from merely GD. We evaluated a total of 28 studies on potential biomarkers for diagnosis of TED. Articles included were published in English, which investigated clinical markers in tear fluid, orbital adipose-connective tissues, orbital fibroblasts and extraocular muscles, serum, thyroid tissue, as well as imaging biomarkers. Results demonstrated that biomarkers with reported diagnostic power have high sensitivity and specificity for TED, including those using a combination of biomarkers to differentiate between TED and GD, as well as the use of magnetic resonance imaging (MRI). Other biomarkers which were upregulated include cytokines, proinflammatory markers, and acute phase reactants in subjects with TED, which are however, deemed less specific to TED. Further clinical investigations for these biomarkers, scrutinising their specificity and sensitivity on a larger sample of patients, may point towards selection of suitable biomarkers for aiding detection and prognosis of TED in the future.

Lycium barbarum polysaccharide promotes corneal Re-epithelialization after alkaline injury.

Chemical injury of the cornea results in epithelial defect and subsequent stromal scarring and infection. Our study aims to evaluate the effectiveness of pre-treatment of Lycium barbarum polysaccharide (LBP) in promoting corneal re-epithelialization after alkaline burn. The corneas of C57BL/6J mice were pre-treated with topical phosphate-buffered saline or LBP (0.2/2/20 mg/mL) for 7 days, following by 0.1M sodium hydroxide injury for 30 s and washing with distilled water for another 30 s. Area of epithelial defect and thickness of cornea were evaluated. Inflammatory cytokines and water channel expression levels were assessed using immunohistochemistry and Western blot. Compared to the injury group, mice with 2 mg/mL LBP pre-treatment revealed a significant decrease in fluorescein stained area after injury (p = 0.025), with increased epithelial layer thickness (p = 0.004). The corneal opacity was significantly reduced in the group with 2 mg/mL LBP pre-treatment followed by injury (p = 0.02). The expression of matrix metalloproteinase 12 (p = 0.033), platelet derived growth factor-BB (p = 0.031), and aquaporin 5 (p = 0.022) resulted in a decrease in expression level in group with 2 mg/mL LBP pre-treatment. Our results showed that 2 mg/mL LBP, with no apoptotic effect on corneal cells, promoted corneal epithelial growth and minimized disruption of the collagen architecture after injury in vivo. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option for patients highly susceptible to ocular injury.

Optical coherence tomography angiography of the macular microcirculation in acute primary angle closure treated with phacoemulsification.

PURPOSE: To measure the changes of macular microcirculation in cases with unilateral acute primary angle closure (APAC) who were managed by phacoemulsification. METHODS: Patients with unilateral APAC and managed by phacoemulsification were enrolled. The contralateral unaffected eyes were served as fellow group, and normal individuals were recruited as control group. Optical coherence tomography angiography (OCT-A) was performed to analyze the macular whole image vessel density (wiVD) and parafoveal vessel density (pfVD). The retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thicknesses were assessed using spectral-domain optical coherence tomography. RESULTS: A total of 36 APAC patients and 35 eyes from 35 normal individuals were recruited. In the APAC eyes, the mean wiVD (42.1% ± 3.7%) and pfVD (45.2% ± 3.8%) in the superficial layers (wiVD-SL and pfVD-SL) were both significantly reduced, compared to fellow eyes (45.7% ± 3.1%, 48.7% ± 3.1%) and control eyes (44.4% ± 4.7%, 47.4% ± 5.1%) (P < 0.05). They were all statistically correlated with RNFL, GCC, visual field pattern standard deviation (PSD), and mean deviation (MD). CONCLUSION: The macular OCT-A parameters including wiVD-SL and pfVD-SL were significantly reduced in the eyes with APAC compared to the fellow unaffected eyes and normal control eyes. They were correlated well with RNFL, GCC, PSD and MD. The macular vessel density parameters may help monitor the progression of APAC.

The anti-scarring role of Lycium barbarum polysaccharide on cornea epithelial-stromal injury.

PURPOSE: Cornea epithelial-stromal scarring is related to the differentiation of fibroblasts into opaque myofibroblasts. Our study aims to assess the effectiveness of Lycium barbarum polysaccharide (LBP) solution as a pre-treatment in minimizing corneal scarring. METHODS: Human corneal fibroblasts were cultured in a three-dimensional collagen type I-based hydrogel in an eye-on-a-chip model. Fibroblasts were pre-treated with 2 mg/mL LBP for 24 h, followed by another 24-h incubation with 10 ng/mL transforming growth factor-beta 1 (TGF-ß1) to induce relevant physiological events after stromal injury. Intracellular pro-fibrotic proteins, extracellular matrix proteins, and pro-inflammatory cytokines that involved in fibrosis, were assessed using immunocytochemistry and enzyme-linked immunosorbent assays. RESULTS: Compared to the positive control TGF-ß1 group, LBP pre-treated cells had a significantly lower expression of alpha-smooth muscle actin, marker of myofibroblasts, vimentin (p < 0.05), and also extracellular matrix proteins both collagen type II and type III (p < 0.05) that can be found in scar tissues. Moreover, LBP pre-treated cells had a significantly lower secretion of pro-inflammatory cytokines interleukin-6 and interleukin-8 (p < 0.05). The cell-laden hydrogel contraction and stiffness showed no significant difference between LBP pre-treatment and control groups. Fibroblasts pretreated with LBP as well had reduced angiogenic factors expression and suppression of undesired proliferation (p < 0.05). CONCLUSION: Our results showed that LBP reduced both pro-fibrotic proteins and pro-inflammatory cytokines on corneal injury in vitro. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option prior to corneal refractive surgeries with an improved prognosis.

A Systematic Review on Cornea Epithelial-Stromal Homeostasis.

INTRODUCTION: This review aims to summarise the role of different cells, genes, proteins and lipid in regulating cornea epithelial-stromal homeostasis. METHODS: We performed an Entrez PubMed literature search using keywords "human," "cornea," "epithelial," "stromal," "homeostasis," "fibrosis response," and "pathogenesis" on 24th of September 2019, resulting in 35 papers, of which 18 were chosen after filtering for "English language" and "published within 10 years" as well as curation for relevance by the authors. RESULTS: The 18 selected papers showed that corneal epithelial cells, fibroblasts and telocytes, together with genes such as Klf4, Pax6 and Id found in the cells, play important roles in achieving homeostasis to maintain corneal integrity and transparency. Proteins classified as pro-fibrotic ligands and anti-fibrotic ligands are responsible for regulating cornea stromal fibrosis and extracellular matrix deposition, thus regulators of scar formation during wound healing. Anti-inflammatory ligands and wound repairing ligands are critical in eliciting protective inflammation and promoting epithelial healing, respectively. Protein receptors located on cellular membrane play a role in maintaining intercellular connections as well as corneal hydration. DISCUSSION/CONCLUSION: These studies prompt development of novel therapeutic strategies such as tear drops or ointments that target certain proteins to maintain corneal homeostasis. However, more in vitro and in vivo studies are required to prove the effectiveness of exogenous administration of molecules in improving healing outcome. Hence, future investigations of the molecular pathways highlighted in this review will reveal novel therapeutic tools such as gene or cell therapy to treat corneal diseases.

Changes in circumpapillary retinal vessel density after acute primary angle closure episode via OCT angiography.

PURPOSE: To investigate the changes and evaluate the diagnosis value of circumpapillary vessel density (VD) in cases of acute primary angle closure (APAC). DESIGN: Case-control study. METHODS: APAC patients with a history of unilateral acute attack were enrolled. The eyes with acute episode constituted the case group while the contralateral eyes without attack consisted of the control group. Ophthalmic examinations including slit-lamp examination, best-corrected visual acuity, intraocular pressure and visual field were carried out. Retinal nerve fiber layer (RNFL), macular ganglion cell complex (GCC) were measured by spectral-domain optical coherence tomography, while VD was assessed by optical coherence tomography angiography. RESULTS: The whole en face image vessel density (wiVD), circumpapillary vessel density (cpVD) and inside disk VD for both all vessels and capillary were all significantly lower in the APAC eyes compared to the fellow eyes (P < 0.01 for all). In APAC eyes, the wiVD, inside disk VD and cpVD both for all vessels and capillary were all positively correlated with RNFL and GCC thicknesses but negatively correlated with the mean deviation (MD), pattern standard deviation (PSD) and the duration of acute attack (all P < 0.01). From the ROC curve, the cpVDcap, wiVDcap, cpVDall and wiVDall all showed comparable diagnostic ability with RNFL, GCC and MD to differentiate eyes with APAC from the fellow eyes (all P > 0.05). The inside disk VDcap and VDall demonstrated significant lower diagnostic ability than the cpVDcap, wiVDcap, cpVDall and wiVDall (all P < 0.001). CONCLUSIONS: In APAC eyes, circumpapillary VD decreased significantly compared with the fellow unaffected eyes. They were significantly correlated with thicknesses of RNFL and GCC, and visual field MD and PSD in the APAC eyes. The patients with longer duration of acute attack were more likely to have lower cpVD. For APAC, the diagnostic ability of wiVD and cpVD was similar with RNFL, GCC and MD and was higher than inside disk VD.

On-Demand Droplet Collection for Capturing Single Cells.

Droplet-based microfluidic techniques are extensively used in efficient manipulation and genome-wide analysis of individual cells, probing the heterogeneity among populations of individuals. However, the extraction and isolation of single cells from individual droplets remains difficult due to the inevitable sample loss during processing. Herein, an automated system for accurate collection of defined numbers of droplets containing single cells is presented. Based on alternate sorting and dispensing in three branch channels, the droplet number can be precisely controlled down to single-droplet resolution. While encapsulating single cells and reserving one branch as a waste channel, sorting can be seamlessly integrated to enable on-demand collection of single cells. Combined with a lossless recovery strategy, this technique achieves capture and culture of individual cells with a harvest rate of over 95%. The on-demand droplet collection technique has great potential to realize quantitative processing and analysis of single cells for elucidating the role of cell-to-cell variations.

Long term outcomes of cataract surgery in severe and end stage primary angle closure glaucoma with controlled IOP: a retrospective study.

BACKGROUND: To investigate the long term surgical outcomes of cataract surgery in severe and end stage glaucoma patients with preoperative intraocular pressure less than 21 mmHg, and to detect the associated factors. METHODS: A retrospective study of primary angle closure glaucoma patients was conducted on who underwent cataract surgery or combined with goniosynechialysis from March 2015 to April 2018. Main outcome measures were visual acuity, intraocular pressure, number of glaucoma medications and complications. RESULTS: Sixteen patients (19 eyes) were included. The mean age was 64.89 ± 11.68 years and the mean followed up duration was 21.89 ± 7.85 months. The final visual acuity was significantly improved from 0.69 ± 0.55 to 0.46 ± 0.52 logMAR, within 12 (63.2%) eyes improved, 4 (21.1%) eyes kept unchanged, and 3 (15.8%) eyes reduced. Linear regression analysis indicated that higher mean deviation, higher visual field index and lower glaucoma stage associated with better final visual acuity (r = - 0.511, r = - 0.493, r = 0.537 respectively). Moreover, the final number of medications were reduced from 1.26 ± 0.99 to 0.26 ± 0.56 (p < 0.01). The mean intraocular pressure was not significantly reduced with the final IOP of 14.48 ± 3.74 mmHg (p = 0.97). While the eyes with intraocular pressure above 15 mmHg was decreased to 6 (31.6%) eyes compared to 10 (52.6%) eyes at baseline. Moreover, the number of eyes free of medications was increased from 4 (21.1%) preoperatively to 15 (78.9%) eyes postoperatively. CONCLUSIONS: Final visual acuity was significantly improved in the severe and end stage primary angle closure glaucoma patients and the number of eyes came off medications increased by 57.8% after cataract surgery. Preoperatively, the glaucoma stage, mean deviation and visual field index are important parameters to predict the final visual acuity after cataract surgery.

A Systematic Review of Emerging Therapeutic Strategies in the Management of Chemical Injuries of the Ocular Surface.

OBJECTIVES: To evaluate recent in vivo studies on emerging therapies for managing corneal epithelial injuries. METHODS: The search was conducted on PubMed for articles published between January 2015 and September 2019 and in English language. RESULTS: Thirty studies were identified for evaluation, including those on mesenchymal stem cells, amniotic membrane-derived therapies, endogenous peptides and their inhibitors, as well as hydrogel therapies. Intermediate to strong levels of evidence are presented regarding the use of these strategies on chemically injured cornea, including their effects on healing of corneal epithelial defect, anti-inflammatory properties, prevention of corneal neovascularization, as well as restoration of anatomy and functions of the anterior eye, although clinical trials are needed to determine the safety and efficacy of these strategies on humans. CONCLUSION: Recent advances and understanding in various novel therapeutic methods for corneal epithelial chemical injuries should provide potential alternatives to current standard treatment regimens and help reduce risks of complications, hence improve patient outcomes.

Ciliochoroidal detachment after Ahmed glaucoma valve implantation: a retrospective study.

BACKGROUND: To investigate the occurrence of ciliochoroidal detachment (CCD), its risk factors and its impact on the success rate after Ahmed glaucoma valve (AGV) implantation. METHODS: This is a retrospective observational study carried out at Eye Hospital of Wenzhou Medical University, Zhejiang, China. Patients with uncontrolled glaucoma who underwent AGV implantation alone or combined with phacoemulsification (AGV-Phaco) in the hospital from April 1, 2013 to July 31, 2016 were included. The preoperative and postoperative CCD was defined when the detachment between ciliary body and choroid was detected by the ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) respectively. The main outcomes included the incidence of CCD and the success rate at 6 months after surgery. RESULTS: In total, 97 male and 56 female patients were included. CCD was observed in 92 (57.8%) eyes. The glaucoma diagnosis in the Non-CCD and CCD group included primary open angle glaucoma (21(31.3%) vs 33(35.9%)), primary angle closure glaucoma (10(14.9%) vs 13(14.1%)), secondary glaucoma (25(37.3%) vs (28(30.4%)) and so on. The preoperative median IOP (interquartile range) were 21.7(16.0,32.0) mmHg and 23.0(16.0,33.0) mmHg in the Non-CCD group and CCD group. Previous surgical history (95% confidence interval (CI), 1.24 to 13.34; odds ratio (OR) 4.06; p = 0.02) and shorter axial length (95% CI, 0.62 to 0.97 OR 0.78; p = 0.02) were the two risk factors of CCD. The success rate between the CCD and Non-CCD group was not significantly different (64.3% vs 62.5%, p = 0.86) at 6 months. CONCLUSIONS: The incidence of CCD is 57.8% after AGV surgery. Eyes with previous surgical procedure was prone to CCD occurrence and longer axial length was protective against CCD. But at 6 months postoperatively, CCD did not reduce the success rate of AGV surgery and may not be a worrisome complication.

Quantifying silicone oil emulsification in patients: are we only seeing the tip of the iceberg?

PURPOSE: Emulsification of silicone oil in the eye is a difficult problem. In an effort to find an objective way to quantify emulsification, we used the Coulter principle to measure silicone oil emulsified droplets from the washings of a series of patients. METHODS: Aqueous washouts after silicone oil removal were obtained from nine patients (nine eyes). We used the Coulter counter Multisizer® 4 to obtain the size distribution of the oil droplets. RESULTS: Over 65 % of the emulsified silicone oil droplets in the clinical samples had a diameter smaller than is detectable by light microscopy (2 µm). The median size of the droplets was between 1.1 and 1.9 µm. Based on the Spearman's correlation coefficient (r), there was a strong correlation between the number of the droplets that cannot be seen (between 1 and 2 µm) and those that can be seen (7-30 µm) (r = 0.817, p = 0.007). CONCLUSION: Once emulsification was detected clinically in the anterior chamber, extensive emulsification would have already occurred in the posterior chamber, with most of the emulsified droplets that were too small in size to be seen on clinical examination. Ostwald ripening might explain why there were so many small droplets. The predominance of small droplets might account for some of the clinical complications associated with silicone oil use.

All-aqueous microfluidic printing of multifunctional bioactive microfibers promote whole-stage wound healing.

Wound healing involves multi-stages of physiological responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Satisfying all demands throughout different stages remains a rarely addressed challenge. Here we introduce an innovative all-aqueous microfluidic printing technique for fabricating multifunctional bioactive microfibers, effectively contributing to all four phases of the healing process. The distinctive feature of the developed microfibers lies in their capacity to be printed in a free-form manner in the aqueous-two phase system (ATPS). This is achieved through interfacial coacervation between alkyl-chitosan and alginate, with enhanced structural integrity facilitated by simultaneous crosslinking with calcium ions and alginate. The all-aqueous printed microfibers exhibit exceptional performance in terms of cell recruitment, blood cell coagulation, and hemostasis. The inclusion of a dodecyl carbon chain and amino groups in alkyl-chitosan imparts remarkable antimicrobial properties by anchoring to bacteria, complemented by potent antibacterial effects of encapsulated silver nanoparticles. Moreover, microfibers can load bioactive drugs like epidermal growth factor (EGF), preserving their activity and enhancing therapeutic effects during cell proliferation and tissue remodeling. With these sequential functions to guide the whole-stage wound healing, this work offers a versatile and robust paradigm for comprehensive wound treatment, holding great potential for optimal healing outcomes.

Antibacterial and Angiogenic (2A) Bio-Heterojunctions Facilitate Infectious Ischemic Wound Regeneration via an Endogenous-Exogenous Bistimulatory Strategy.

In infectious ischemic wounds, a lack of blood perfusion significantly worsens microbe-associated infection symptoms and frequently complicates healing. To overcome this daunting issue, antibacterial and angiogenic (2A) bio-heterojunctions (bio-HJs) consisting of CuS/MXene heterojunctions and a vascular endothelial growth factor (VEGF)-mimicking peptide (VMP) are devised and developed to accelerate infectious cutaneous regeneration by boosting angiogenesis via an endogenous-exogenous bistimulatory (EEB) strategy. Assisted by near-infrared irradiation, the bio-HJ platform exhibits versatile synergistic photothermal, photodynamic, and chemodynamic effects for robust antibacterial efficacy. In addition, copper ions liberated from 2A bio-HJs elevate VEGF secretion from fibroblasts, which provokes VEGF receptors (VEGFR) activation through an endogenous pathway, whereas VMP itself promotes an exogenous pathway to facilitate endothelial cell multiplication and tube formation by directly activating the VEGFR signaling pathway. Moreover, employing an in vivo model of infectious ischemic wounds, it is confirmed that the EEB strategy can considerably boost cutaneous regeneration through pathogen elimination, angiogenesis promotion, and collagen deposition. As envisaged, this work leads to the development of a powerful 2A bio-HJ platform that can serve as an effective remedy for bacterial invasion-induced ischemic wounds through the EEB strategy.

Engineered Bio-Heterojunction Confers Extra- and Intracellular Bacterial Ferroptosis and Hunger-Triggered Cell Protection for Diabetic Wound Repair.

Nanomaterial-mediated ferroptosis has garnered considerable interest in the antibacterial field, as it invokes the disequilibrium of ion homeostasis and boosts lipid peroxidation in extra- and intracellular bacteria. However, current ferroptosis-associated antibacterial strategies indiscriminately pose damage to healthy cells, ultimately compromising their biocompatibility. To address this daunting issue, this work has designed a precise ferroptosis bio-heterojunction (F-bio-HJ) consisting of Fe2 O3 , Ti3 C2 -MXene, and glucose oxidase (GOx) to induce extra-intracellular bacteria-targeted ferroptosis for infected diabetic cutaneous regeneration. Fe2 O3 /Ti3 C2 -MXene@GOx (FMG) catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria, facilitating the permeation of synchronously generated Fe2+ /Fe3+ into bacteria under near-infrared (NIR) irradiation, causing planktonic bacterial death via ferroptosis, Fe2+ overload, and lipid peroxidation. Additionally, FMG facilitates intracellular bacterial ferroptosis by transporting Fe2+ into intracellular bacteria via inward ferroportin (FPN). With GOx consuming glucose, FMG creates hunger protection which helps macrophages escape cell ferroptosis by activating the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway. In vivo results authenticate that FMG boosts diabetic infectious cutaneous regeneration without triggering ferroptosis in normal cells. As envisaged, the proposed tactic provides a promising approach to combat intractable infections by precisely terminating extra-intracellular infection via steerable ferroptosis, thereby markedly elevating the biocompatibility of therapeutic ferroptosis-mediated strategies.

Achieving Clearance of Drug-Resistant Bacterial Infection and Rapid Cutaneous Wound Regeneration Using an ROS-Balancing-Engineered Heterojunction.

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /V2C MXene bio-heterojunctions (2D2-bioHJs) is devised. Under ultrasonication, 2D2-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D2-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.