Bacterial infections occur frequently during the implantation of medical devices, and functional coating is one of the effective means to prevent and remove biofilms. In this study, three different hydrophilic polyoxazolines with carboxyl groups (aPOx: PT1, PT2 and PT3) and bactericidal silver nanoparticles (AgNPs) were synthesized successfully, and an aPOx-AgNP multilayer film was prepared by electrostatic layer-by-layer self-assembly. The effect of charge density and assembly solution concentration was explored, and the optimal self-assembly parameters were established (PT2 1 mg/mL and AgNPs 3 mg/mL). The hydrophilicity of the surface can be enhanced to resist protein adhesion if the outermost layer is aPOx, and AgNPs can be loaded to kill bacteria, thereby realizing the bactericidal anti-adhesion potential integration of the aPOx-AgNP multilayer film. In addition, the aPOx-AgNP multilayer film was found to have the characteristic of intelligent and efficient pH-responsive silver release, which is expected to be used as a targeted anti-biofilm surface of implantable medical devices.

Tumor resection and prosthetic replacement have become the treatments of choice for malignant bone tumors. Infections are the leading cause of failure of limb salvage surgeries. Therefore, treating infections around prostheses after limb salvage is essential and challenging. Our research team designed a "domino" sequential treatment plan to treat postoperative infections around tumor prostheses and evaluated its efficacy. To introduce the new domino sequential treatment plan for postoperative infections of tumor prostheses, and evaluate the technical points of the plan and prognosis in medium- and long-term follow-ups. Between January 2015 and August 2021, 14 patients were treated with prosthesis-preserving domino sequential therapy for peripheral prosthesis infections after bone-tumor limb salvage. The sample included eight cases of distal femur tumor, two of proximal tibia tumor, three of pelvic tumor, and one of middle femur tumor. We evaluated routine blood test results, C-reactive protein level, the erythrocyte sedimentation rate, and other indicators. X-rays and CT scans of the surgical site were obtained and the Musculoskeletal Tumor Society (MSTS) score was calculated. Treatment involved debridement and lavage of the prosthesis, and systemic and local antibiotics. The positivity rate of microbial culture was 78.6%. There were three cases of Staphylococcus aureus, one of Staphylococcus epidermidis, two of methicillin-resistant Staphylococcus epidermidis, one of methicillin-resistant Staphylococcus aureus, two of Acinetobacter baumannii, one of Streptococcus lactis (group C), one of Streptococcus mitis, and three with negative cultures. In three cases, sequential treatment failed to control the infection. The operation success rate was 78.6% (11/14). One case eventually required amputation, and another required long-term wound dressings. To control the infection, a third had to be treated using antibiotic bone cement combined with the "intramedullary nail reverse double insertion" technique. The MSTS scores of patients before infection debridement and at the last follow-up showed statistically significant differences (t = 5.312, p = 0.02). The prosthesis-preserving domino sequential method has certain advantages for treating bone-tumor limb salvage infections around the prosthesis. Level IV, therapeutic.

Bone defect represents one of the most prevalent clinical conditions in orthopedics diseases, and the key to successful therapeutic outcomes lies in achieving early vascularization coupled with late-phase osteogenic differentiation. Growth factor delivery is among the most widely adopted strategies for bone tissue regeneration. However, achieving the spatiotemporal coupled regulation of vascularized bone regeneration remains a major challenge. Proprotein convertase subtilisin/kexin type 9 (PCSK9) exerts a pivotal role in bone metabolism. Our preliminary findings demonstrated that PCSK9 expression is upregulated during bone regeneration, while the supplementation of exogenous PCSK9 can enhance the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSC). Based on these findings, we fabricated a composite hydrogel by adsorbing PCSK9 onto vascular-derived extracellular matrix (ECM) and incorporating vascular endothelial growth factor (VEGF) into gelatin methacryloyl (GelMA). Taking advantage of the distinct sustained-release profiles of these biomaterials, this hydrogel system was engineered to recapitulate the natural bone defect healing process, thereby enabling the coupled regulation of accelerated early vascularization and enhanced late-phase osteogenic differentiation. Both in vitro and in vivo experimental results confirmed that the constructed composite hydrogel can further potentiate the therapeutic efficacy of PCSK9 and achieve efficient vascularized bone regeneration. Mechanistically, our findings revealed that PCSK9 promotes the osteogenic differentiation of BMMSC via activation of the ERK signaling pathway. Collectively, the PCSK9- and VEGF-loaded composite hydrogel exhibits promising pro-angiogenic and pro-osteogenic coupling capabilities for bone regeneration, which provides novel therapeutic targets and innovative strategies for the clinical management of bone defects.