Xingtao Chen

Osteoporosis (OP), characterized by reduced bone mass and microstructural deterioration, poses a significant global health burden. Current therapies, such as bisphosphonates (e.g., alendronate, Aln), face challenges, including low bioavailability, systemic toxicity, and lack of targeting. Herein, we developed an erythrocyte membrane (EM)-cloaked Prussian blue (PB) nanoparticle system (EAP) coloaded with Aln to address these therapeutic bottlenecks. The hollow PB core functions as a peroxidase-mimetic catalyst, efficiently scavenging reactive oxygen species (ROS) through Fe³⁺/Fe²⁺ redox cycling. Meanwhile, the EM cloaking endows the system with prolonged blood circulation and active bone targeting via integrin receptor-mediated recognition. The EAP exhibits pH-responsive drug release profiles and significant ROS elimination capacity (H₂O₂: 82.9%; ·OH: 80.2%; O₂·^-: 85.1%). The EAP can regulate in vitro osteoclast-osteoblast balance by suppressing osteoclastogenesis and promoting osteoblast mineralization. In an ovariectomized aged mouse model, EAP treatment restored bone density and trabecular microarchitecture comparable to sham controls, with histological analysis demonstrating no observable systemic toxicity. Transcription and protein expression analysis revealed downregulated NF-κB/MAPK signaling and osteoclast-specific markers after EAP treatment. This biomimetic nanodelivery system integrates ROS scavenging and targeted drug delivery, providing a potential strategy for OP therapy and other inflammatory bone disorders.

Multi-functionalization of wound dressings with natural polymers is meaningful and remains a challenge. The combination of natural polyanions and polycations appears to be a promising strategy. Still, its performances based on current layer-by-layer self-assembly or homogeneous complexation are mutable and limited. Herein, Ca²⁺-incorporated carboxymethyl cellulose (Ca/Na-CMC) and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) are adopted as the model polyanion and polycation, respectively, to develop multi-functionalized dressings based on interfacial complexation. The dressings exhibit a multilayer structure composed of a polyanion layer (Ca/Na-CMC) for hemostasis and promotion of cell proliferation, a formed polyelectrolyte complex (PEC) layer for structural stability, and a polycation layer (HACC) for antibiosis. Compared to the dressing based on homogeneous complexation, the multilayer dressings show stronger moisture penetrability (around 1,150 g/m²/24 h), higher hemostatic activity, and higher antibacterial rate (up to 100%) and promoted effect on cell proliferation. An in vivo evaluation using a rat full-thickness skin defect model reveals that the multilayer dressings can accelerate wound healing in 2 weeks. Overall, owing to interfacial complexation resulting in separate layers, the performances of polyanions and polycations after combination are more predictable, and their biological functions can be effectively preserved. These findings not only support the extensive application of multilayer dressings but also offer an alternative strategy for multi-functionalizing wound dressings with natural polyanions and polycations.

Zinc can enhance osteoblastic bone formation and stimulate osteogenic differentiation, suppress the differentiation of osteoclast precursor cells into osteoclasts, and inhibit pathogenic bacterial growth in a dose-dependent manner. In this study, simonkolleite, as a novel zinc resource, was coated on poly (amino acids) (PAA) via suspending PAA powder in different concentrations of zinc chloride (ZnCl₂) solution, and the simonkolleite-coated PAA (Zn–PAA) was characterized by SEM, XRD, FT-IR and XPS. Zinc ions were continuously released from the coating, and the release behavior was dependent on both the concentration of the ZnCl₂ immersing solution and the type of soak solutions (SBF, PBS and DMEM). The Zn–PAA was cultured with mouse bone marrow stem cells (BMSCs) through Transwell^TM plates, and the results indicated that the relative cell viability, alkaline phosphatase (ALP) activity and mineralization of BMSCs were significantly higher with Zn–PAA as compared to PAA. Moreover, the Zn–PAA was cultured with RAW264.7 cells, and the results suggested an inhibiting effect of Zn–PAA on the cell differentiation into osteoclasts. In addition, Zn–PAA exhibited an antibacterial activity against both S. aureus and E. coli. These findings suggest that simonkolleite coating with certain contents could promote osteogenesis, suppress osteoclast formation and inhibit bacteria, indicating a novel way of enhancing the functionality of synthetic bone graft material and identifying the underline principles for designing zinc-containing bone grafts.

Absorbable hemostatic agents with a high hemostatic efficacy play an important role in surgical and severely traumatic hemostasis. In the present study, by applying polyelectrolyte assembly, polyelectrolyte complexes (PECs), using carboxymethyl starch (CMS) and chitosan oligosaccharide (COS), with controllable physicochemical properties were prepared and optimized for hemorrhage control. Particle size, zeta potential, morphology and water absorption of the PECs with different CMS/COS ratios were systematically evaluated. The results of in vitro degradation in PBS suggested that CMS/COS PECs were degradable and their degradation rates, which decreased with the increase of the COS content, were suitable for absorbable hemostatic agents. The in vivo hemostatic efficacy of the PECs with 10 wt% COS content (PEC 10), which was evaluated in a rabbit hepatic hemorrhage model, was better than CMS but decreased with the increase of the COS content. The plasma coagulation evaluation revealed that the PECs could significantly activate and accelerate the coagulation cascade through both the intrinsic and extrinsic pathways but could not directly affect the common pathway. CMS/COS PECs also showed antimicrobial activity against S. aureus, which enhanced with the increase of the COS content, but failed against E. coli. Moreover, PEC 10 displayed excellent cytocompatibility with MC3T3-L1 and good tissue compatibility in a rabbit liver model. These findings not only suggest that CMS/COS PECs with a suitable COS content were promising absorbable hemostatic agents for internal use but they are also useful to understand the underlying principles for designing PEC based hemostatic agents.