After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. In this study, the curcumin (Cur) loaded chitosan (CS) nanoparticles (CCNP) encapsulated silk fibroin (SF)/hyaluronic acid esterified by methacrylate (HAMA) (CCNPs-SF/HAMA) hydrogel for the osteosarcoma therapy and bone regeneration was developed by photocuring and ethanol treatment. The micro or nanofibers networks were observed in the CCNPs-SF/HAMA hydrogel. The FTIR results demonstrated that alcohol vapor treatment caused an increase in β-sheets of SF, resulting in the high compression stress and Young’s modulus of CCNPs-SF/HAMA hydrogel. According to the water uptake analysis, SF caused a slight decrease in water uptake of CCNPs-SF/HAMA hydrogel while CCNPs could enhance the water uptake of it. The swelling kinetic results showed that both the CCNPs and the SF increased the swelling ratio of CCNPs-SF/HAMA hydrogel. The accumulative release profile of CCNPs-SF/HAMA hydrogel showed that the release of Cur from CCNPs-SF/HAMA hydrogel was accelerated when pH value was decreased from 7.4 to 5.5. Besides, compared with CCNPs, the CCNPs-SF/HAMA hydrogel had a more sustainable drug release, which was beneficial for the long-term treatment of osteosarcoma. In vitro assay results indicated that CCNPs-SF/HAMA hydrogel with equivalent Cur concentration of 150 μg/mL possessed both the effect of anti-cancer and promoting the proliferation of osteoblasts. These results suggest that CCNPs-SF/HAMA hydrogel with superior physical properties and the bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.

Bacterial infections have a serious impact on public health. It is urgent to develop antibacterial hydrogels with good biocompatibility to reduce the use of antibiotics. In this study, poly(lipoic acid-co-sodium lipoate)–phytic acid (P(LA-SL)-PA) hydrogels are prepared by a simple mixture of the natural small molecules lipoic acid (LA) and phytic acid (PA) in a mild and green reaction environment. The crosslinking network is constructed through the connection of covalent disulfide bonds as well as the hydrogen bonds, which endow the injectable and self-healing properties. The P(LA-SL)-PA hydrogels exhibit an adjustable compression modulus and adhesion. The in vitro agar plates assay indicates that the antibacterial rate of hydrogels against Escherichia coli and Staphylococcus aureus is close to 95%. In the rat-infected wound model, the P(LA-SL)-PA hydrogels adhere closely to the tissue and promote epithelialization and collagen deposition with a significant effect on wound healing. These results prove that the P(LA-SL)-PA hydrogels could act as effective wound dressings for promoting the healing of infected wounds.

Integrating bioactive function with wound-status indication remains a major challenge in the design of hydrogel dressings for complex wound management. Most pH-responsive hydrogels still rely on separate bioactive and sensing components, leading to increased compositional and fabrication complexity and highlighting the need for unified platforms based on a single bioactive molecule with intrinsic pH responsiveness. In this work, a multifunctional SF/HA/Rhe hydrogel dressing was developed by incorporating rhein (Rhe), a plant-derived small molecule, into a silk fibroin/hyaluronic acid (SF/HA) matrix. Rhe served as a single functional component that simultaneously endowed the hydrogel with antibacterial, antioxidant and pH-responsive colorimetric properties. The optimized SF/HA/Rhe hydrogel achieved antibacterial rates above 94% against Staphylococcus aureus, Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). It also exhibited strong antioxidant activity, with an ABTS radical scavenging rate of 87.22% and effective reduction of intracellular ROS accumulation. In addition, the hydrogel showed a distinct pH-dependent colorimetric response over the wound-relevant pH range of 5.5–7.5, allowing visual indication of local pH variations. The SF/HA/Rhe hydrogel further displayed favorable mechanical performance and biocompatibility, with cell viability above 90% and hemolysis below 5%. Overall, these findings provide a feasible strategy for multifunctional hydrogel dressings with integrated antibacterial, antioxidant and visual pH monitoring.