No abstract

The complex tissue‐specific physiology that is orchestrated from the nano‐ to the macroscale, in conjugation with the dynamic biophysical/biochemical stimuli underlying biological processes, has inspired the design of sophisticated hydrogels and nanoparticle systems exhibiting stimuli‐responsive features. Recently, hydrogels and nanoparticles have been combined in advanced nanocomposite hybrid platforms expanding their range of biomedical applications. The ease and flexibility of attaining modular nanocomposite hydrogel constructs by selecting different classes of nanomaterials/hydrogels, or tuning nanoparticle‐hydrogel physicochemical interactions widely expands the range of attainable properties to levels beyond those of traditional platforms. This review showcases the intrinsic ability of hybrid constructs to react to external or internal/physiological stimuli in the scope of developing sophisticated and intelligent systems with application‐oriented features. Moreover, nanoparticle‐hydrogel platforms are overviewed in the context of encoding stimuli‐responsive cascades that recapitulate signaling interplays present in native biosystems. Collectively, recent breakthroughs in the design of stimuli‐responsive nanocomposite hydrogels improve their potential for operating as advanced systems in different biomedical applications that benefit from tailored single or multi‐responsiveness.

The ability to correctly mimic the complexity of the tumor microenvironment in vitro is a key aspect for the development of evermore realistic in vitro models for drug-screening and fundamental cancer biology studies. In this regard, conventional spheroid-based 3D tumor models, combined with spherically structured biomaterials, opens the opportunity to precisely recapitulate complex cell-extracellular matrix interactions and tumor compartmentalization. This review provides an in-depth focus on current developments regarding spherically structured scaffolds engineered into in vitro 3D tumor models, and discusses future advances toward all-encompassing platforms that may provide an improved in vitro/in vivo correlation in a foreseeable future.

Bottom‐up tissue engineering is a promising approach for designing modular biomimetic structures that aim to recapitulate the intricate hierarchy and biofunctionality of native human tissues. In recent years, this field has seen exciting progress driven by an increasing knowledge of biological systems and their rational deconstruction into key core components. Relevant advances in the bottom‐up assembly of unitary living blocks toward the creation of higher order bioarchitectures based on multicellular‐rich structures or multicomponent cell–biomaterial synergies are described. An up‐to‐date critical overview of long‐term existing and rapidly emerging technologies for integrative bottom‐up tissue engineering is provided, including discussion of their practical challenges and required advances. It is envisioned that a combination of cell–biomaterial constructs with bioadaptable features and biospecific 3D designs will contribute to the development of more robust and functional humanized tissues for therapies and disease models, as well as tools for fundamental biological studies.

Three-dimensional (3D) cell culture models of solid tumors are currently having a tremendous impact in the in vitro screening of candidate anti-tumoral therapies. These 3D models provide more reliable results than those provided by standard 2D in vitro cell cultures. However, 3D manufacturing techniques need to be further optimized in order to increase the robustness of these models and provide data that can be properly correlated with the in vivo situation. Therefore, in the present study the parameters used for producing multicellular tumor spheroids (MCTS) by liquid overlay technique (LOT) were optimized in order to produce heterogeneous cellular agglomerates comprised of cancer cells and stromal cells, during long periods. Spheroids were produced under highly controlled conditions, namely: (i) agarose coatings; (ii) horizontal stirring, and (iii) a known initial cell number. The simultaneous optimization of these parameters promoted the assembly of 3D characteristic cellular organization similar to that found in the in vivo solid tumors. Such improvements in the LOT technique promoted the assembly of highly reproducible, individual 3D spheroids, with a low cost of production and that can be used for future in vitro drug screening assays.