No abstract

Magnesium phosphate cement (MPC) has been evaluated as an inorganic bone filler due to its favorable biocompatibility, biodegradability, rapid setting, high initial strength, and osteogenic potential. However, the setting time of MPC is so rapid that it makes it difficult to use in practice, and the clinical properties of MPC could be further be improved by adding bioactive materials. Here we developed novel bioactive chondroitin sulfate (CS)-MPC composites (CS-MPCs) by incorporating different amounts of CS into MPC. The compositions, microstructures, and physiochemical properties of CS-MPCs and their induced in vitro cellular responses and in vivo bone regeneration properties were evaluated. CS-MPCs had a longer setting time, lower hydration temperature, higher compressive strength, and more neural pH than MPC. CS-MPCs demonstrated similar degradation ratios relative to MPC in Tris-HCl solution. CS-MPCs promoted pre-osteoblast cell proliferation, attachment, and differentiation in vitro and enhanced bone formation surrounding implants in vivo. In conclusion, through CS modification, our novel CS-MPCs have improved physiochemical properties that enhance compatibility in vitro and bone regeneration in vivo, making them attractive materials for bone regeneration.

Incorporating bioactive substances into synthetic bioceramic scaffolds is challenging. In this work, oxygen-carboxymethyl chitosan (O-CMC), a natural biopolymer that is nontoxic, biodegradable and biocompatible, was introduced into magnesium potassium phosphate cement (K-struvite) to enhance its mechanical properties and cytocompatibility. This study aimed to develop O-CMC/magnesium potassium phosphate composite bone cement (OMPC), thereby combining the optimum bioactivity of O-CMC with the extraordinary self-setting properties and mechanical intensity of the K-struvite. Our results indicated that O-CMC incorporation increased the compressive strength and setting time of K-struvite and decreased its porosity and pH value. Furthermore, OMPC scaffolds remarkably improved the proliferation, adhesion and osteogenesis related differentiation of MC3T3-E1 cells. Therefore, O-CMC introduced suitable physicochemical properties to K-struvite and enhanced its cytocompatibility for use in bone regeneration.

Osteosarcoma is the most common malignant bone tumor, and although there has been significant progress in its management, metastases often herald incurable disease. Here we defined genes differentially expressed between primary and metastatic osteosarcoma as metastasis-related genes (MRGs) and used them to construct a novel six-MRG prognostic signature for overall survival of patients with osteosarcoma. Validation in internal and external datasets confirmed satisfactory accuracy and generalizability of the prognostic model, and a nomogram based on the signature and clinical variables was constructed to aid clinical decision-making. Of the six MRGs, FHIT is a well-documented tumor suppressor gene that is poorly defined in osteosarcoma. Consistent with tumor suppressor function, FHIT was downregulated in osteosarcoma cells and human osteosarcoma samples. FHIT overexpression inhibited osteosarcoma proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, FHIT overexpression upregulate the epithelial marker E-cadherin while repressing the mesenchymal markers N-cadherin and vimentin. Our six-MRG signature represents a novel and clinically useful prognostic biomarker for patients with osteosarcoma, and FHIT might represent a therapeutic target by reversing epithelial to mesenchymal transition.