The present study aimed to investigate the effects of cold atmospheric plasma (CAP)-activated Ringer's solution on osteosarcoma cell lines MG63 and U2OS, and to identify the molecular mechanism underlying these effects. CAP-activated Ringer's solution was used to treat osteosarcoma cell lines MG63 and U2OS for 30 min. Cell viability was measured using the MTT method. The apoptosis rate was detected using Annexin-V and propidium iodide. The expression levels of cytochrome c, caspase-3 and polyADP ribose polymerase (PARP) in MG63 cells were analyzed via western blotting. The change in mitochondrial membrane potential was detected via the JC-1 dye method and verified by the level of reactive oxygen species (ROS). CAP-activated Ringer's solution inhibited the proliferation of MG63 and U2OS cells in a dose-and time-dependent manner. Furthermore, CAP-activated Ringer's solution induced the apoptosis of MG63 cells, increased the intracellular ROS level, decreased the mitochondrial membrane potential level, and induced the release of cytochrome c. CAP-activated Ringer's solution inhibits osteosarcoma cell proliferation through intracellular ROS-mediated mitochondrial apoptosis.

The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly( d , l -lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the in vitro and in vivo release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.

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BackgroundReconstruction of pelvis girdle stability after tumor-induced hemipelvectomy remains challenging. We surgically treated 13 patients with custom-made, three-dimensional printed hemipelvic prostheses. We aim to identify the preliminary outcomes for patients who have been managed with more mixed regions of prosthetic pelvic reconstruction and the feasibility of two reconstructive systems.MethodsSeven male patients and 6 female patients treated at our center between January 2019 and May 2021 were included. There were 11 primary sarcomas and 2 solitary bone metastases. After en bloc tumor resection, two types of personalized, three-dimensional printed prostheses were fixed to restore the stability and rebuild the load transfer. The position of the reconstructed hemipelvis was evaluated on an anteroposterior plain radiograph. The complications and outcomes were traced. One amputation specimen was discovered through histological analysis of the porous structure.ResultsThe operative duration was 467 ± 144 min, and the blood loss was 3,119 ± 662 ml. During a follow-up of 22.4 ± 8.5 months, two patients had delayed wound healing and one had a second-stage flap transfer. One patient with osteosarcoma died of pulmonary metastasis 27 months after surgery. Two patients with marginal resection suffered from local recurrence and had extra surgeries. One patient had traumatic hip dislocation 2 months after surgery and manipulative reduction was performed. The acetabular inclination of the affected side was 42.2 ± 4.3°, compared with 42.1 ± 3.9° on the contralateral side. The horizontal distance between the center of the femoral head and the middle vertical line was 10.4 ± 0.6 cm, while the reconstructed side was 9.8 ± 0.8 cm. No significant difference in acetabular position after surgery was found (p > 0.05). The amputation specimen harvested from one patient with local recurrence demonstrated bone and soft tissue ingrowth within the three-dimensional printed trabecular structure. Walking ability was preserved in all patients who are still alive and no prosthesis-related complications occurred. The MSTS score was 22.0 ± 3.7.ConclusionsBoth types of custom-made, three-dimensional printed prostheses manifested excellent precision, mechanical stability, and promising functional rehabilitation. The porous structure exhibited favorable histocompatibility to facilitate the ingrowth of bone and soft tissue.

Background: Prosthetic reconstruction after type I + II+ III internal hemipelvectomy remains challenging due to the lack of osseointegration and presence of giant shear force at the sacroiliac joint. The purpose of this study was to evaluate the biomechanical properties of the novel 3D-printed, custom-made prosthesis with pedicle screw–rod system and sacral tray using finite element analysis.Methods: Four models that included one intact pelvis were established for validation. Forces of 500 N and 2,000 N were applied, respectively, to simulate static bipedal standing and the most loaded condition during a gait cycle. Biomechanical analysis was performed, and the results were compared; the preliminary outcomes of four patients were recorded.Results: For the reconstructed hemipelvis, stress was mainly concentrated on the sacral screws, bone–prosthesis interface, and upper endplate of the L5 vertebra. The optimization of the design with the sacral tray structure could decrease the peak stress of the sacral screws by 18.6%, while the maximal stress of the prosthesis increased by 60.7%. The addition of the lumbosacral pedicle–rod system further alleviated stress of the sacral screws and prosthesis by 30.2% and 19.4%, respectively. The site of peak stress was contemporaneously transferred to the connecting rods within an elastic range. In the retrospective clinical study, four patients who had undergone prosthetic reconstruction were included. During a follow-up of 16.6 ± 7.5 months, the walking ability was found preserved in all patients who are still alive and no prosthesis-related complications had occurred except for one hip dislocation. The Musculoskeletal Tumor Society (MSTS) score was found to be 19.5 ± 2.9.Conclusion: The novel reconstructive system yielded favorable biomechanical characteristics and demonstrated promising preliminary outcomes. The method can be used as a reference for reconstruction after type I + II + III hemipelvectomy.