Abstract The healing process of chronic wounds is often hindered by recurring bacterial infections, inflammation, and inadequate tissue regeneration, which necessitates the development of innovative dressing materials capable of both infection detection and treatment. Herein, we report the development of a coaxial nanofiber scaffold made up of PCL-gelatin integrated with copper-doped prussian blue nanoparticles (CuPB), bromothymol blue (BTB), and mesenchymal stem cells (MSCs) for concurrent pH-sensitive detection of infection, drug delivery, and tissue regeneration. The coaxial architecture allowed compartmentalized integration of functional elements within the scaffold while preserving its biomimetic fibrous structure for wound dressing application. The release of CuPB nanoparticles, which serve as the source of the antibacterial copper component, imparted antibacterial properties, while BTB facilitated visual colorimetric detection of infection-associated pH changes, allowing real-time monitoring of wound status. The addition of the MSCs further augmented the regenerative potential of the scaffold through the paracrine mediated modulation of inflammation, angiogenesis, and extracellular matrix remodeling. In vitro assessment indicated the cytocompatibility, MSC compatibility, and hemocompatibility of the scaffold, with hemolysis less than 2%. In vivo assessment revealed that MSC-loaded CuPB-BTB coaxial nanofibers promoted wound healing more efficiently than the control group. Histological and immunohistochemical analyses further revealed improved tissue organization, enhanced angiogenesis as evidenced by VEGF expression, and increased α-SMA associated tissue remodeling. Hence, this multifunctional scaffold represents a promising theranostic wound dressing capable of integrating infection monitoring, antibacterial action, and MSC-mediated tissue regeneration for chronic wound management.
Abstract Polydopamine (PDA) deposition is often described as “substrate-independent,” yet its early-stage kinetics on chemically well-defined interfaces remain insufficiently quantified. Here, we employ average visible-light transmittance as a rapid, non-destructive at-line kinetic probe to monitor PDA film formation over short timescales (1–20 min) on model hydrophilic (–OH) and hydrophobic (–CH3) surfaces. Combined characterization reveals that wettability governs the initial nucleation and growth modes of PDA and thereby determines the evolution of optical responses and film microstructure. On hydrophobic interfaces, PDA undergoes Volmer–Weber (island-like) growth, producing rapid nucleation, pronounced early transmittance attenuation, and higher surface roughness. In contrast, hydrophilic interfaces favor Frank–van der Merwe-like (layer-by-layer) growth, leading to smoother, denser films and a delayed late-stage “oxidation burst.” As a result, the transmittance–time profiles establish a quantitative link between microscopic interfacial processes and macroscopic optical signals, enabling identification of the transition from nucleation-dominated to later-stage growth behavior. Functionality assays further show that coatings derived from hydrophobic substrates exhibit superior antibacterial performance (>99.9% reduction against E. coli and S. aureus), while maintaining good cytocompatibility (cell viability > 90%). This work elucidates the interfacial dependence of PDA assembly and introduces a simple, optics-based paradigm for rapid at-line process monitoring and quality control in coating technologies. Growth-mode terminology is used throughout as a descriptive analogy for the observed morphological and kinetic sequence, not as a claim of heteroepitaxial thermodynamic growth modes.
The coumarin-based fluorophore, 7-(diethylamino-3-(5-(trifluoromethyl)benzo[d]thiazol-2-yl)-2H-chromen-2-one (DTBTC), as synthesized in this work, exhibits excellent potential as a multifunctional photosensitizer for bioimaging and photodynamic therapy. DTBTC enables confocal cellular imaging at an exceptionally low concentration of 500 nM and efficiently generates reactive oxygen species under light irradiation, producing potent photocytotoxicity with IC50 values of 332 and 646 nM against HeLa and MCF-7 monolayer cells, respectively. It also demonstrates significant therapeutic efficacy in the corresponding tumors pheroid models (IC50 < 20 μM). Compared with reference compounds R1 [7-(diethylamino)-2-oxo-2H-chromene-3-carboxylic acid] and R2 [coumarin-3-carboxylic acid], DTBTC displays distinctive aggregation-dependent photophysical behavior. In solution, it exhibits bright green emission with a high photoluminescence quantum yield (81.14%), a narrow emission bandwidth (FWHM = 41 nm), and a small Stokes shift (39 nm), characteristic of monomeric emission. Upon aggregation, the appearance of a dominant blueshifted absorption band (449 nm) and a weaker redshifted band (491 nm) indicates the coexistence of H- and T-type aggregates. While H-aggregates promote emission quenching, T-aggregates give rise to orange-red emission. This aggregation-sensitive luminescence further enables fluorescence turn-off detection of acids (acid detection threshold corresponds to an estimated pH of ~6.01) in water, with high sensitivity even toward weak acids such as acetic acid.
The development of advanced three-dimensional (3D) scaffolds for cancer modeling and drug screening remains a critical need in biomedical engineering. Most 3D printed scaffolds for cell growth focus on a tessellated design involving sequentially deposited printed fibers. Although this design offers a high degree of flexibility in scaffold dimensions, including fiber width and inter-fiber spacing, continuous voids in the Z-axis require additional methods to avoid cell sedimentation to the underlying substrate such as the incorporation of support materials. In this work, we present a modified design strategy based on the rotation of the internal infill pattern between successive layers. This strategy yields tessellated scaffolds that significantly improve cell retention and spatial cell distribution with no need for additional support matrices. Using this optimized design, we developed a 3D breast cancer model to investigate chemotherapeutic resistance by comparing MDA-MB-231 cells and their corresponding cancer stem cells, under paclitaxel treatment. The incorporation of gold nanorods in the scaffold matrix allowed us to perform real-time, in situ drug monitoring via surface-enhanced Raman scattering (SERS) sensing. These tessellated plasmonic scaffolds enable the evaluation of chemoresistance by tracking differential drug accumulation in 3D.
Triple-negative breast cancer (TNBC) is a heterogeneous type of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Because of the lack of ER, PR, and HER2 targets, TNBC is unsuitable for endocrine therapy and HER2-targeted therapy and is associated with a higher risk of early recurrence, distant metastasis, and poorer prognosis than many other breast cancer subtypes, particularly in advanced or metastatic disease. Although surgery, chemotherapy, radiotherapy, and immunotherapy have been used for TNBC treatment, current therapeutic outcomes remain limited by systemic toxicity, high recurrence rates, insufficient tumor selectivity, and acquired drug resistance. Therefore, novel approaches are needed to address these challenges. Nanomaterials with optical, magnetic, catalytic, and porous properties can serve as imaging contrast agents, drug carriers, photosensitizers, nanozymes, radiosensitizers, and multifunctional theranostic platforms. However, the clinical translation of TNBC-oriented nanomedicines remains limited because of insufficient patient stratification, variable tumor accumulation, unclear long-term biosafety, and challenges in scalable manufacturing. To improve the clinical application of nanotechnology in TNBC treatment, it is imperative to integrate nanotechnology with existing clinical diagnosis and treatment methods. This integration may help overcome the limitations of individual diagnostic and therapeutic methods, enhance tumor targeting and radiotherapy sensitivity, reduce cytotoxicity and drug resistance, and maximize the efficiency of multimodal diagnosis and treatment.
