This study presents the development and characterization of cellulose acetate (CA) and CA reinforced with 5 wt % hydroxyapatite (CAHA5) as printable bioinks for extrusion-based 3D printing of scaffolds targeting bone tissue engineering. The printed scaffolds were evaluated for morphology, mechanical performance, surface characteristics, and biological response. Scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, and energy-dispersive X-ray spectroscopy (EDS) confirmed scaffold integrity and successful HA incorporation, while contact angle, degradation, and swelling measurements revealed tunable surface wettability and fluid uptake. Mechanical testing under compression and tension showed that HA incorporation reduced strength and increased brittleness compared to pure CA, while stiffness values remained within reported ranges for printed scaffolds. Biological assays using mice mesenchymal stem cells (MSCs) showed favorable adhesion and osteogenic differentiation, particularly on CAHA5 scaffolds. These findings suggest that CAHA5 bioinks offer a promising route for fabricating biocompatible and osteoinductive scaffolds, where enhanced bioactivity is achieved despite a moderate reduction in mechanical strength compared to pure CA.

The fabrication of synergistic antimicrobial surfaces traditionally relies on complex, multi-component formulations that are often plagued by inherent compatibility and stability challenges. Herein, we report a "single-component" hybrid agent, quaternized cuprous oxide (Cu2O@QPEI), synthesized via a polyethyleneimine-mediated hydrothermal assembly followed by N-alkylation. The resulting material features hierarchical "raspberry-like" microspheres comprising a polycationic QPEI shell chemically anchored to a Cu2O core. Exhibiting intrinsic synergy, Cu2O@QPEI achieves complete S. aureus (1 × 106 CFU mL-1) eradication within 6 h at a low minimum lethal concentration (MLC) of 5 μg mL-1, significantly outperforming single-mode controls. The mechanism involves a "Breach-and-Payload" strategy, where the shell disrupts the bacterial membrane to facilitate rapid copper ion ingress. When incorporated into a topical hydrogel (5 μg g-1), the hybrid significantly accelerated wound healing and reduced infection in a murine model. This work presents a "single-component agent" strategy to overcome traditional formulation challenges, offering a promising platform for developing next-generation synergistic antimicrobial materials for healthcare and industrial applications.

Tuberculosis (TB) remains a major global public health challenge, while current first-line regimens are often compromised by drug resistance, high toxicity, and poor targeting. Herein, we develop a lesion-pathogen dual-targeting theranostic nanoparticle (ICG-PEG-Tar) for imaging-guided photothermal therapy (PTT). The ICG enables fluorescence/photothermal imaging while serving as the photothermal agent, and the anti-Ag85B (marked as Tar in ICG-PEG-Tar NPs) precisely targets antigen 85B of Mycobacterium tuberculosis. The binding specificity of ICG-PEG-Tar NPs toward Ag85B was validated by ELISA, confirming the molecular recognition capability of the conjugated antibody on ICG-PEG-Tar NPs. The therapeutic efficacy is systematically evaluated in a well-established murine tail granuloma model induced by Mycobacterium marinum (M.m), a pathogen phylogenetically close to Mycobacterium tuberculosis. While the M.m murine tail granuloma has inherent limitations in fully mimicking human pulmonary TB, it remains a widely used surrogate that recapitulates key human tuberculosis hallmarks, including caseating granulomas and conserved virulence determinants. Importantly, it offers the practical advantage of BSL‑2 operability with direct laser access. Upon administration, ICG-PEG-Tar first passively accumulates at granuloma lesions by extravasating via leaky vasculature of inflamed granulomas, a process analogous to the enhanced permeability and retention (EPR) effect, and then actively binds to M.m through anti-Ag85B recognition. Under laser irradiation, the nanoparticles generate potent localized hyperthermia that effectively ablates viable M.m, achieving a 96.5% reduction in bacterial CFU counts in vitro and significantly suppressing granuloma progression in vivo. Moreover, real‑time infrared thermal imaging confirmed that the PTT effect was precisely confined to the granuloma site, with the surrounding healthy tissue temperature remaining within the normal physiological range throughout the irradiation period, indicating a favorable safety profile. Overall, the nanoparticles demonstrate excellent targeting specificity, robust antibacterial efficacy against M.m, prolonged lesion-site retention, and favorable biocompatibility, collectively offering a paradigm for precise TB management.

Heavy-metal-based nano-objects have been recently shown to act as radiosensitizers. One possible underlying mechanism causing this effect is the amplification of reactive oxygen species (ROS) production upon irradiation. This reaction could be utilized to improve radiotherapy by repolarizing M2 anti-inflammatory macrophages, which typically constitute the majority of the tumor-associated macrophage population, to the M1 pro-inflammatory phenotype that induces anti-cancer responses, as ROS upregulation has been associated with M1 polarization. This study employs gold nanoparticles (AuNPs) of sizes of 15 or 50 nm, coated with polyvinylpyrrolidone (PVP) or polyethylene glycol. These AuNPs upregulated M1 gene expression and favored the polarization effect of 5 Gy and 10 Gy X-ray irradiation but not of 5 or 10 Gy proton irradiation. Furthermore, 50 nm AuNPs coated with PVP reduced the survival of M2 co-cultured with pancreatic cancer cells, used alone or in combination with 5 Gy X-rays. The findings confirm that AuNPs combined with X-ray radiotherapy can repolarize TAMs to become more M1-like and cytotoxic to pancreatic cancer cells. This work presents an efficient and easy-to-manufacture technique to improve radiotherapy efficacy in solid cancers like pancreatic cancer.

Tissue adhesives are increasingly utilized for wound closure in various clinical settings that could either replace or augment more traditional options, such as sutures and patches. Biocompatible hydrogels capable of providing a physical barrier and ample hydration are increasingly utilized for this purpose. However, hydrogels often lack sufficient adhesive and cohesive strengths compared to traditional adhesives, especially under a hydrated environment. In this study, a thermoresponsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel was developed as a pressure-sensitive adhesive using a catechol-modified acrylic hyperbranched polyglycerol crosslinker ('CAHPG'). The presence of both acrylate and catechol on HPG enhances the mechanical properties of the PNIPAm hydrogel by chemical crosslinking of acrylate and physical interaction of catechol with the surrounding PNIPAm chains, while the adhesive properties are mainly conferred by catechol. More notably, the adhesiveness of the PNIPAm-CAHPG hydrogels is "activated" above the transition temperature of PNIPAm due to the thermoresponsive deswelling driven by the increased hydrophobicity, removing the hydration layer at the interface to maximize the adhesive interaction. This unique characteristic of the PNIPAm-CAHPG hydrogel, coupled with the ability to deliver therapeutic agents to further promote wound healing, is demonstrated to be highly suited for "on-demand" tissue adhesive applications.

Bacterial infections pose a significant threat to human health with traditional antibiotic therapies increasingly failing to achieve desirable efficacy. Consequently, the development of therapeutic strategies has become a research focus, with multimodal synergistic antibacterial approaches receiving increasing attention due to their marked advantages. Herein, we present a ruthenium-manganese dinuclear complex, Ru(mfibpy)Mn, which enables visible light-triggered cogeneration of carbon monoxide (CO) and singlet oxygen (1O2) with the self-reporting monitoring capability. Spectroscopic studies reveal that upon λmax = 410 nm irradiation, the antibacterial reagent precisely induces the release of CO by Mn-CO bond cleavage and 1O2 produced by the Ru(II)-complex moiety while restoring intrinsic MLCT luminescence, which facilitates real-time tracking of the generation process through the turn-on luminescence of the Ru(II)-complex. In vitro experiments demonstrate that the synergistic antibacterial effect significantly enhances efficacy compared to monofunctional systems, achieving complete eradication of both Gram-negative and Gram-positive bacteria at concentrations as low as 1 μM under 10 min of light exposure and effectively disrupting drug-resistant bacterial biofilms. Furthermore, in vivo studies in a murine-infected wound model confirm its potent therapeutic efficacy. This work successfully developed a multifunctional molecular tool based on transition metal complexes with both antibacterial and tissue-regenerative capabilities, offering an insight for development of antibacterial reagents and bacterial infection treatment.

Most infectious diseases are caused by pathogenic infections, which pose significant threats to human health due to their ubiquitous presence and high transmissibility. While antibiotics initially demonstrated excellent therapeutic effects, their widespread misuse has led to the emergence of drug-resistant pathogens, creating even greater challenges. Conventional therapeutic agents often struggle to balance efficacy with biosafety. Organic conjugated molecules (OCM) have attracted considerable attention owing to their excellent biocompatibility and photophysical properties. This has led to the development of phototherapy, which offers numerous advantages including non-invasiveness, avoidance of drug resistance, low toxicity, and superior therapeutic outcomes. Currently widely applied in biomedical fields, phototherapy has seen numerous design strategies emerging in recent years that have yet to be systematically reviewed. This review comprehensively summarizes the latest research advances over the past five years in OCM design strategies and major phototherapeutic approaches for antimicrobial applications. We categorize and discuss current research achievements according to different phototherapy modalities, with particular focus on treatments for superficial tissue infections (e.g., wound, periodontal, and intraocular infections). Simultaneously, we critically analyze the innovation, limitations, and practical applicability of various studies, while also outlining potential challenges for future development in phototherapy.

Efficient and organ-selective delivery remains a major challenge for messenger RNA (mRNA) therapeutics, motivating extensive material design efforts across diverse delivery systems. Here, we report a simple formulation-based strategy to control the physicochemical properties and in vivo biodistribution of mRNA polyplexes using an amphiphilic polyaspartamide derivative bearing cationic diethylenetriamine (DET) and hydrophobic 2-cyclohexylethyl (CHE) side chains, PAsp(DET/CHE). Systematic modulation of the molar ratio of polyaspartamide amine to mRNA phosphate (N/P) revealed that polyplex size and surface potential strongly influence biodistribution following systemic administration. The physicochemical properties of mRNA polyplexes could also be adjusted by incubation with physiological saline, 150 mM NaCl. This post-assembly modulation induced controlled particle growth without mRNA release, resulting in a marked shift in tropism from lung- to spleen-selective mRNA expression, accompanied by preferential accumulation in antigen-presenting cells. The NaCl-processed polyplexes elicited robust antigen-specific humoral and cellular responses following ovalbumin (OVA) mRNA delivery. These findings demonstrate that fine-tuning the ionic environment provides a facile means to control mRNA polyplex assembly and in vivo distribution, offering a scalable route to organ-selective mRNA delivery systems for vaccination and beyond.

Biodegradable hydrogels are promising for bone regeneration but are limited by a significant mechanical mismatch with bone tissue in modulus, strength, and toughness. To address the weakness, this work reported a mesh-like hydrogel woven from calcium-alginate gel fibers. The fibers, manufactured via wet-spinning, possessed tensile strengths (36-285 MPa) and moduli (200 MPa-9.1 GPa) comparable to those of bone tissue. This feature made the woven hydrogel withstand complex physiological loads while maintaining its biodegradable properties. In vitro, the degraded hydrogel promoted the osteogenic differentiation of rat bone mesenchymal stem cells, achieving 155% increment of alkaline phosphatase (ALP) activity and 294% increment of mineralized calcium nodules. After implantation into cranial bone defects in vivo, complete biodegradation resulted in continuous release of bioactive calcium, significantly accelerating bone regeneration and achieving a regenerated bone volume to tissue volume (BV/TV) ratio of 67.2%. This study demonstrates a paradigm of degradation-mediated nutrient release, highlighting the pivotal role of bioactive calcium delivery for effective bone regeneration.