Osteoporotic bone defects refer to the disruption of bone structural integrity in patients with osteoporosis and pose a substantial challenge to orthopedic surgeons. In this study, we developed a biomimetic hydrogel to improve the osteogenic microenvironment and promote stem cell homing. This hydrogel served as a container for S-nitrosoglutathione and Ca ²⁺ , promoting the release of bioactive nitric oxide (NO) from bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells and activating the NO/cyclic guanosine monophosphate signaling pathway. These changes promote osteogenic and angiogenic couplings. The hydrogel simultaneously recruited BMSCs by conjugating the stem cell homing peptide SKPPGTSS. Using a rat distal femoral defect model, it was demonstrated that this hydrogel can effectively increase the formation of bone tissue and new blood vessels and has immune-regulating functions. We envision that this hydrogel may be a minimally invasive yet highly effective strategy for expediting the healing of osteoporotic bone defects.

With the increase in antibiotic resistance, the development of new antibacterial agents is urgent. Photosensitizers with no detectable resistance are promising antibacterial agents. However, most photosensitizers are insoluble, structurally unstable and ineffective against Gram-negative bacteria due to their negatively charged cell wall that hinder their use. In this study, a novel bacteria-activated photosensitizer ionic liquid was designed and assembled to improve the solubility, stability and antibacterial ability of photodynamic therapy. The cation 1-vinyl-3-dodecyl imidazole has been designed, which has strong binding energy with the major constituent of the cell wall. The anion selected was chlorin e6 (Ce6) since it could respond to the acidic microenvironment of bacterial infection. The Ce6 ionic liquid (Ce6-IL) composed of 1-vinyl-3-dodecyl imidazole and Ce6 not only exhibited bacteria-activated ability because its cation could firmly bond with peptidoglycan in the cell wall, but also had excellent acid responsive ability due to the protonation reaction of COO⁻ in its anion. The binding energy of the cation with peptidoglycan was calculated via molecular dynamics simulation, and the pH-responsive behavior of Ce6-IL was verified via HR-MS. The surface potential, mechanical property, morphology and uptake rate results indicated that the cation could destroy the cell wall and promote the anion Ce6 to enter the bacteria. Due to the dual-mode antibacterial action of its cation and anion, Ce6-IL was more effective against Gram-negative and Gram-positive bacteria than Ce6 alone and had wide-spectrum antibacterial ability. The in vitro studies showed that the IC₅₀ of Ce6-IL against E. coli and S. aureus was reduced by 100 and 10 times, respectively. Furthermore, the in vivo studies indicated that Ce6-IL was more effective for eliminating bacterial infection and could accelerate wound healing. The compatibility test showed that Ce6-IL had low toxicity and exhibited excellent biocompatibility.