Hyaluronic acid (HA) exists naturally as an important component of the extracellular matrix (ECM) in the human body. In recent decades, HA has been widely used in bone regeneration, and is currently a popular topic, particularly in the craniofacial and dental fields. From maxilla augmentation to craniofacial bone trauma, there is now a large demand for bone regenerative therapy. Serving as a cell-seeding scaffold or a carrier for bioactive components, hyaluronic acid-incorporated scaffolds and carriers in bone regeneration can be fabricated into either rigid or colloidal forms. Since the type of material used is a critical factor in the biological properties of a scaffold, HA derivatives or HA-incorporated composite scaffolds have shown excellent potential for improving osteogenesis and mineralization. Furthermore, in order to better enhance osteogenesis, local delivery carriers based on hyaluronic acid derivatives, rather than specifically serving as scaffolds, can be established by loading different osteoinductive or osteogenetic components and acquiring different release patterns. Such osteoinductive carriers immobilized on implant surfaces are also effective in improving osseointegration. Thus, as such a competent biomaterial, hyaluronic acid should be considered a promising tool in bone regeneration.

The chemotherapy of stimuli-responsive drug delivery systems (SDDSs) is a promising method to enhance cancer treatment effects. However, the low efficiency of chemotherapy drugs and poor degradation partly limit the application of SDDSs. Herein, we report doxorubicin (DOX)-loading mixed micelles for biotin-targeting drug delivery and enhanced photothermal/photodynamic therapy (PTT/PDT). Glutathione (GSH)-responsive mixed micelles were prepared by a dialysis method, proportionally mixing polycaprolactone-disulfide bond-biodegradable photoluminescent polymer (PCL-SS-BPLP) and biotin-polyethylene glycol-cypate (biotin-PEG-cypate). Chemically linking cypate into the mixed micelles greatly improved cypate solubility and PTT/PDT effect. The micelles also exhibited good monodispersity and stability in cell medium (~119.7 nm), low critical micelles concentration, good biodegradation, and photodecomposition. The high concentration of GSH in cancer cells and near-infrared light (NIR)-mediated cypate decomposition were able to achieve DOX centralized release. Meanwhile, the DOX-based chemotherapy combined with cypate-based NIR-triggered hyperthermia and reactive oxygen species could synergistically induce HepG2 cell death and apoptosis. The in vivo experiments confirmed that the micelles generated hyperthermia and achieved a desirable therapeutic effect. Therefore, the designed biodegradable micelles are promising safe nanovehicles for antitumor drug delivery and chemo/PTT/PDT combination therapy.

To evaluate the effects of simvastatin in a new injectable microsphere hydrogel system on bone healing process of tooth sockets. Simvastatin was loaded in poly (lactic-co-glycolic acid) (PLGA) microspheres using an emulsion process, and the drug-loaded PLGA microspheres were further entrapped in a gelatin hydrogel to form an injectable microsphere-hydrogel system. Simvastatin-free hydrogel and blank microspheres hydrogel were used as controls. A rat tooth extraction socket model was generated, and the simvastatin-loaded microsphere-hydrogel composite was injected in the defect area of a tooth socket. At 1, 2, 5, and 8 weeks after the surgery, all the animals were sacrificed and the mandibles were harvested. The samples were examined using X-ray, hematoxylin and eosin staining, and histological evaluations. Five weeks after the surgery, significantly more bone tissue was formed in the simvastatin-loaded hydrogel group than in the simvastatin-free hydrogel group and the blank microspheres hydrogel group as control (p < 0.05). The injectable simvastatin-loaded microsphere hydrogel promoted new bone formation in the tooth extraction socket after 5 weeks, and has a promising potential for bone repair and regeneration.

Oral squamous cell carcinoma (OSCC) remains a formidable challenge due to high recurrence rates and limited efficacy of conventional treatments. Immunotherapy holds potential, but its effectiveness is often restricted by low patient responsiveness. This study presents a novel therapeutic strategy using GSH/pH-responsive copper-based cascade nanocomplexes to induce immunogenic cell death (ICD) in OSCC. The fabricated nanocomplex, PC@B-H, leverages the acidic and reducing tumor microenvironment to release copper ions and plumbagin, triggering a cascade of cell death mechanisms including cuproptosis, ferroptosis, and necroptosis. This multifunctional system not only enhances oxidative stress but also depletes glutathione, promotes lipid peroxidation, and disrupts mitochondrial function, leading to robust tumor inhibition. Additionally, the induction of ICD facilitates dendritic cell maturation and cytotoxic T lymphocyte infiltration, providing durable anti-tumor immunity. The study demonstrates that PC@B-H achieves a 92.3 % tumor growth inhibition rate with minimal systemic toxicity, offering a promising avenue for enhancing the efficacy of OSCC treatment through combined cell death pathways and immune activation.