Diabetic wounds are frequently complicated by persistent bacterial infection, excessive reactive oxygen species (ROS) accumulation, and dysregulated inflammation, which collectively reinforce a hostile microenvironment that delays tissue repair. Herein, we report a glucose-responsive hydrogel platform (GL@PGB) for local delivery of gallium-luteolin nanocomplexes (GL NCs), designed to couple Ga-associated antibacterial metal-homeostasis perturbation with luteolin-associated oxidative-inflammatory regulation. In this system, the PVA/guar gum/borax (PGB) hydrogel functions as a hemostatic and wound-adaptive delivery matrix, enabling local retention and glucose-accelerated release of GL NCs under hyperglycemic conditions. The released GL NCs suppressed bacterial growth and disrupted established biofilms, and transcriptomic analysis suggested perturbation of metal-ion homeostasis and genetic information-processing pathways in S. aureus. Concurrently, GL@PGB reduced intracellular ROS accumulation and promoted macrophage polarization toward a reparative phenotype in vitro. In an S. aureus-infected diabetic full-thickness wound model, GL@PGB reduced bacterial burden, alleviated inflammatory responses, and promoted collagen deposition and angiogenesis, thereby improving wound repair. These results suggest that GL@PGB may serve as a glucose-responsive local delivery system for disrupting bacterial metal homeostasis while reshaping the infection-ROS-inflammation microenvironment.
Cell-specific intracellular delivery of messenger RNA (mRNA) remains a challenge in the development of RNA therapeutics. Photochemical internalization (PCI) is a useful technology for the spatially controllable cytosolic delivery of such molecules in a light-selective manner, but cellular-level precision has yet to be realized due to the intrinsic amphiphilicity of conventional photosensitizers (PSs). Here, we report that a polymer conjugate bearing phenylboronic acid (PBA) moieties in the side chain can be utilized as a PS delivery system for cell-specific PCI. At extracellular pH, the PBA moieties can form boronate esters with l-3, 4-dihydroxyphenylalanine (L-DOPA), and this PS-polymer with L-DOPA shows hydrophilicity and achieves selective internalization into cancer cells through amino acid transporter-mediated endocytosis. The acidic pH of endo−/lysosomes then cleaves the boronate esters, liberating L-DOPA and inducing a hydrophilic-to-hydrophobic conversion of the polymer. This conversion facilitates the interaction of the polymer with the endo−/lysosomal membrane, which is preferable for PCI. Indeed, the polymer accomplished cell-specific PCI of co-administered mRNA polyplexes with more than 80-fold photoenhancement in cultured cells and achieved light-selective mRNA expression in the tumor tissue of a murine model. The concept of our polymer based on boronic acid chemistry may offer a unique approach to develop mRNA therapeutics.
Distal Weight-Bearing Implants (DWBIs) represent a clinically emerging class of load-bearing medical devices in which biomaterial design, surface architecture, and biomechanical performance are tightly coupled. Their success depends not only on restoring distal support in transfemoral rehabilitation, but also on the ability of metallic, ceramic, and composite biomaterial interfaces to sustain cyclic loading while promoting durable bone-implant integration. However, distal support also changes bending moments, shear stresses, micromotion, coating durability, and biological demands at the bone–implant interface. This systematic review synthesizes DWBI concepts, geometry optimization, finite element analysis with gait-phase loading, Functionally Graded Materials (FGMs), graded Ti–HAp (hydroxyapatite) architectures, in-vivo osseointegration evidence, and clinical translation pathways. A quantitative trend analysis was performed on 34 direct-contribution papers and 32 empirical studies to assess trends, validation depth, and translation readiness. However, more than half of the empirical evidence remained at the bench or simulation level, while animal and human/clinical studies formed a smaller validation layer. HAp-centered surface or bulk material engineering represented a substantial share of the corpus; however, evidence for graded Ti–HAp/FGM architectures was derived predominantly from non-DWBI biomaterial and mechanistic analog studies, supporting mechanistic plausibility rather than DWBI-specific validation. Mechanistically, DWBI should be interpreted as an integrated biomaterial-mechanical system linking macro-geometry, metallic/ceramic surface architecture, graded Ti-HAp interfaces, gait-phase loading, tribology/corrosion behavior, in-vivo fixation, and clinical workflow. Translation will require patient-realistic loading conditions, validated finite element analysis workflows, device-level fatigue and coating-integrity testing, standardized in-vivo endpoints, harmonized rehabilitation protocols, and registry-supported clinical follow-up linking mechanical plausibility to durable biological fixation and patient-level benefit.
As a biodegradable material, magnesium‑gallium (Mg-xGa) alloy has exhibited outstanding antibacterial properties, however, its potential application in postoperative bone tumor repair still necessitates the validation of its antitumor function. In this study, Mg-xGa alloys (x = 0.5, 1.0, and 2.0 wt%) were successfully fabricated via conventional melting. The microstructure, biodegradation behavior, and tensile properties of the alloys were systematically characterized, followed by a comprehensive evaluation of their in vitro and in vivo biocompatibility and antitumor activity. Results demonstrated a uniform distribution of Ga as a solid solution in the Mg matrix, with no detectable second phases formed in the Mg-xGa alloys. Among the alloys, the Mg-2.0Ga alloy displayed optimal comprehensive tensile properties, coupled with a degradation rate of 0.134 mm/year. The Mg-xGa alloys effectively inhibited the proliferation and migration of U2OS and 143B bone tumor cells. This was associated with mitochondrial membrane potential depression, leading to the induction of apoptosis. In addition, the alloys exhibited favorable biocompatibility and osteogenic properties in vitro when co-cultured with MC3T3–E1 osteoblasts. Furthermore, in subcutaneous tumor models, they exhibited excellent antitumor activity and biocompatibility without significant systemic toxicity observed. In summary, the incorporation of an appropriate amount of Ga into Mg effectively inhibits tumorigenic activity in bone tumor cells while maintaining normal cellular functions in healthy cells. This Mg-xGa alloy exhibits broad application prospects in both bone tissue engineering and bone tumor therapy, warranting further exploration of their clinical value.
Chronic and non-healing wounds remain a major clinical challenge due to impaired angiogenesis and insufficient regenerative signaling. Although mesenchymal stem cell (MSC)-derived secretomes offer promise as cell-free therapeutics, clinical translation is hindered by limited regenerative potency and poor localization. Here, we translated Iron–Quercetin complex (IronQ) into a scaffold-integrated priming platform by developing IronQ-incorporated polycaprolactone/poly(ethylene oxide) (PCL/PEO) electrospun nanofibers for adipose-derived stem cell (ADSC) culture and secretome modulation. The optimized PCL/PEO (3:1) scaffold exhibited favorable architecture, mechanical properties, cytocompatibility, and pH−/temperature-responsive IronQ release. Proteomic and cytokine analyses demonstrated that nanofibrous scaffold-based culture, together with IronQ-mediated biochemical stimulation, was associated with changes in ADSC secretory profiles involving extracellular matrix organization and regenerative pathways, with increased levels of selected regenerative mediators, including VEGF-A, HGF, FGF-21, PDGF-AA, SDF-1α, and CCL-2. Functionally, conditioned medium generated from ADSCs cultured on the IronQ-containing scaffold enhanced endothelial proliferation and vascular network formation, as well as fibroblast responses associated with tissue repair in vitro. These findings support the potential of this bioactive nanofibrous platform as a scaffold-based strategy for modulating ADSC paracrine responses relevant to wound-healing applications.
