Osteosarcoma describes a tumor of mesenchymal origin with an annual incidence rate of four to five people per million. Even though chemotherapy treatment has shown success in non-metastatic osteosarcoma, metastatic disease still has a low survival rate of 20%. A targeted therapy approach is limited due to high heterogeneity of tumors, and different underlying mutations. In this review, we will summarize new advances obtained by new technologies, such as next generation sequencing and single-cell sequencing. These new techniques have enabled better assessment of cell populations within osteosarcoma, as well as an understanding of the molecular pathogenesis. We also discuss the presence and properties of osteosarcoma stem cells—the cell population within the tumor that is responsible for metastasis, recurrence, and drug resistance.

Chitosan scaffolds are an effective biologically active material with versatile application in chemistry and medicine. Chitosan is a linear polysaccharide, a derivative of chitin, with great biocompatibility due to the possession of functional groups such as −OH and −NH 2 , which allow for biodegradability and antibacterial function. Chitosan has a polycation nature allowing complex formation with metal ions and many biomolecules such as DNA, proteins and lipids, while its specific structure and functional groups are responsible for antibacterial, hemostatic, and analgesic properties. To improve its angiogenic and antimicrobial potential, chitosan can be modified by boron (borate ions). The aim of this work was to prepare boric acid modified chitosan scaffolds, using boric acid as a boron precursor, as potential bioactive scaffolds for tissue regeneration. Borate ions tend to form complexes with hydroxyl groups, however, such physical interactions between boron and chitosan functional groups result in poor encapsulation efficiency. To ensure higher boron incorporation, chitosan scaffolds were cross-linked by genipin, a cross linker with lower cytotoxicity in contrast to glutaraldehyde commonly used to prepare stable chitosan-based materials. The degree of deacetylation (DD) and concentration of chitosan solution as well as the concentration of a solvent are important parameters that affect the crosslinking process. Moreover, the addition of boric acid could interfere with the crosslinking process by occupying chitosan functional groups. Here, chitosan scaffolds were modified with different concentrations of boric acid, while the concentrations of chitosan solution (1.2 w/v), genipin (2 % w/w), and acetic acid (0.5 % v/v) were kept constant. Obtained scaffolds were characterised by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FTIR), while cytotoxicity was evaluated as a function of materials concentration and exposure time. The results indicated successful incorporation of boron into crosslinked chitosan scaffolds with highly porous structure and low cytotoxicity.

Biologically compatible chitosan-based scaffolds have been considered a promising platform for tissue regeneration, tumor treatment, and targeted drug delivery. Chitosan-based scaffolds can be utilized as pH-sensitive drug carriers with targeted drug delivery resulting in less invasive tumor treatments. Further improvement with bioactive ions, such as borate ions, can result in the dual functionality of chitosan carriers provided by simultaneous antitumor efficacy and tissue regeneration. Here, boric acid-containing crosslinked chitosan scaffolds were prepared as delivery systems of doxorubicin, a chemotherapy drug used in the treatment of osteosarcoma. The encapsulation of boric acid was indicated by FTIR spectroscopy, while the ICP-MS analysis indicated the rapid release of boron in phosphate buffer (pH 6.0) and phosphate-buffered saline solution (pH 7.4). The obtained chitosan-boric acid scaffolds exhibit a highly porous and interconnected structure responsible for high swelling capacity, while enzymatic degradation indicated good scaffolds stability during four weeks of incubation at pH 6.0 and 7.4. Furthermore, the release of doxorubicin investigated in phosphate buffers indicated lower doxorubicin concentrations at pH 7.4 with respect to pH 6.0. Finally, the cytotoxicity of prepared doxorubicin-encapsulated scaffolds was evaluated on human sarcoma cells indicating the scaffolds’ potential as cytostatic agents.

The aim of this work was to prepare bimetallic chitosan microgels with high sphericity and investigate the influences of metal-ion type and content on the size, morphology, swelling, degradation and biological properties of microgels. Amino and hydroxyl groups of chitosan (deacetylation degree, DD, of 83.2% and 96.9%) served as ligands in the Cu2+–Zn2+/chitosan complexes with various contents of cupric and zinc ions. The electrohydrodynamic atomization process was used to produce highly spherical microgels with a narrow size distribution and with surface morphology changing from wrinkled to smooth by increasing Cu2+ ions’ quantity in bimetallic systems for both used chitosans. The size of the bimetallic chitosan particles was estimated to be between 60 and 110 µm for both used chitosans, and FTIR spectroscopy indicated the formation of complexes through physical interactions between the chitosans’ functional groups and metal ions. The swelling capacity of bimetallic chitosan particles decreases as the DD and copper (II) ion content increase as a result of stronger complexation with respect to zinc (II) ions. Bimetallic chitosan microgels showed good stability during four weeks of enzymatic degradation, and bimetallic systems with smaller amounts of Cu2+ ions showed good cytocompatibility for both used chitosans.