RESUMEN
Composite hydrogels have gained great attention as three-dimensional (3D) printing biomaterials because of their enhanced intrinsic mechanical strength and bioactivity compared to pure hydrogels. In most conventional printing methods for composite hydrogels, particles are preloaded in ink before printing, which often reduces the printability of composite ink with little mechanical improvement due to poor particle-hydrogel interaction of physical mixing. In contrast, the in situ incorporation of nanoparticles into a hydrogel during 3D printing achieves uniform distribution of particles with remarkable mechanical reinforcement, while precursors dissolved in inks do not influence the printing process. Herein, we introduced a "printing in liquid" technique coupled with a hybridization process, which allows 3D freeform printing of nanoparticle-reinforced composite hydrogels. A viscoplastic matrix for this printing system provides not only support for printed hydrogel filaments but also chemical reactants to induce various reactions in printed objects for in situ modification. Nanocomposite hydrogel scaffolds were successfully fabricated through this 3D freeform printing of hyaluronic acid (HAc)-alginate (Alg) hydrogel inks through a two-step crosslinking strategy. The first ionic crosslinking of Alg provided structural stability during printing, while the secondary crosslinking of photo-curable HAc improved the mechanical and physiological stability of the nanocomposite hydrogels. For in situ precipitation during 3D printing, phosphate ions were dissolved in the hydrogel ink and calcium ions were added to the viscoplastic matrix. The composite hydrogels demonstrated a significant improvement in mechanical strength, biostability, as well as biological performance compared to pure HAc. Moreover, the multi-material printing of composites with different calcium phosphate contents was achieved by adjusting the ionic concentration of inks. Our method greatly accelerates the 3D printing of various functional or hybridized materials with complex geometries through the design and modification of printing materials coupled with in situ post-printing functionalization and hybridization in reactive viscoplastic matrices.
RESUMEN
Skeletal metastasis is prevalent in many cancers, and has been the subject of intense research, yielding innovative models to study the multiple stages of metastasis. It is now evident that, in the early stages of metastatic spread, disseminated tumour cells in the bone undergo an extended period of growth arrest in response to the microenvironment, a phenomenon known as "dormancy". Dormancy has been implicated with drug resistance, while enforced dormancy has also been seen as a radical method to control cancer, and engineering of dormant states has emerged as a novel clinical strategy. Understanding of the subject, however, is limited by the availability of models to describe early stages of metastatic spread. This mini-review provides a summary of experimental models currently being used in the study of bone metastasis and the applications of these models in the study of dormancy. Current research in developing improved models is described, leading to a discussion of challenges involved in future developments.