ABSTRACT
The management of osteosarcoma (OS) patients presents a significant clinical challenge. Despite progress in conventional and targeted therapies, the survival rate of OS patients remains limited largely due to therapy resistance and the high metastatic potential of the disease. OS models that accurately reflect the fundamental characteristics are vital to the innovation and validation of effective therapies. This review provides an insight into the advances and challenges in OS drug development, focusing on various preclinical models, including cell lines, 3D culture models, murine models, and canine models. The relevance, strengths, and limitations of each model in OS research are explored. In particular, we highlight a range of potential therapeutics identified through these models. These instances of successful drug development represent promising pathways for personalized OS treatment.
ABSTRACT
BACKGROUND: The endoprosthetic knee reconstruction using a current universal femoral stem might not be suitable for local population due to the anatomical difference between Chinese and Western populations. We measured the anatomical parameters of Chinese femurs as reference for stem design, and proposed a cementless, curved, short endoprosthesis stem for the reconstruction of distal femur. This study analyzed the biomechanical performance of the newly designed stem aimed at the identification of better operative strategy. METHODS: The CT-scanning data of femurs derived from 96 healthy Chinese volunteers were imported into the Mimics software, and a segmental measurement strategy was applied to evaluate the radius of curvature (ROC) of the femoral medullary cavity. Then, 4 kinds of endoprosthetic replacement models were created based on the measurement results. Model A: the distal tumor resected femora + straight stem A; Model B: the distal tumor resected femora + curved stem B; Model C: the distal tumor resected femora + curved stem C; Model D: the distal tumor resected femora + curved stem D. Finally, the mechanical difference among these models were compared by finite element analysis. RESULTS: The mean femoral ROC of Segment1, 2, 3, 4, 5 measured in the present study was 724.5 mm, 747.5 mm, 1016.5 mm, 1286.5 mm, and 1128 mm, respectively. Based on the femoral ROC of Segment2, the stem ROC of the curved stem B, C, and D was designed as 475 mm, 700 mm, and 1300 mm, respectively. Generally, all endoprosthetic replacement models showed a normal-like stress distribution on the femurs. However, compared to the straight stem, the biomimetic curved stem showed better biomechanical performance both in terms of reducing the extent of the stress shielding of the femur and in terms of minimizing the stress distribution of the implant. CONCLUSIONS: The uncemented, curved, short stem with suitable ROC can perfectly match the Chinese femoral canal morphology which has better mechanical properties than the conventional femoral stem. Thus, this newly designed femoral stem might be an optimized method for treatment of malignant femoral tumours in the Chinese populations in the case that the numerical results are supported by future experimental studies.
