The work presented here uses apple pomace (AP), an industrial waste from apple juice and cider production as a renewable raw material (RRM), to obtain materials that can be utilized as biocompatible scaffolds for osteoblasts and chondrocytes, employed in tissue engineering, valuable extracts that can be used as nutraceuticals and pectin. All of these have much higher value than the original raw material, pectin can be priced up to 1 euro/g, chlorogenic acid is ca. 120 euros/g, caffeic acid 3-5 euros/g and especially the scaffolds that are usually made by synthetic methods using non-renewable raw materials with high fabrication costs and sold at prices higher than 100 euros/g, while the residues used here have prices lower than 100 euros per ton. Thus, there are clear environmental and financial incentives in transforming this waste material into valuable substances and materials. As indicated in the Graphical Abstract, the procedure followed consists in sequential extractions of antioxidants, pectin and finally the preparation of a biocompatible material, giving priority to the latter due to its importance as a renewable scaffold for tissue engineering. From a literature search, to date, although separate ways of valorisation have been applied to this kind of waste, the sequential multivalorization adopted here, has not been previously attempted. Furthermore, biocompatible scaffolds from AP have not been described.
Additive manufacturing technologies have enabled some of the most relevant advances in the fields of tissue engineering and biofabrication, [1,2] thanks to the solid freeform fabrication opportunities they provide, which prove very adequate for achieving complex geometries capable of interacting in personalized ways with the human body. From pioneering studies dealing with the fused deposition modeling of tissue scaffolds as extracellular matrixes for cells, [3,4] to more recent bioprinting approaches, [5-7] which typically use layer-by-layer fabrication techniques with living organisms and biomaterials to produce complex tissues in vitro [8] (or use computer-aided transfer processes for patterning and assembling living and nonliving materials with a prescribed 2D or 3D organization to produce bio-engineered structures), [9] the possibility of manipulating matter in an additive way has proven transformative. However, additional progress is needed, as there is not yet a single additive manufacturing technique (AMT) that provides the perfect compromise between achievable part size, printing resolution, dimensional operative range, structural stability, and overall biocompatibility. For instance, syringe-based bioprinting techniques are still less precise than the more traditional AMTs working with synthetic materials, which are already a mainstream trend in biomedical engineering, medical practice, and biotechnology fields (i.e., selective laser sintering or melting of metallic powders, laser stereolithography with biophotopolymers or lithography-based ceramic manufacturing, among others). [10-12] Other biomanufacturing techniques, such as laser-assisted bioprinting has led to an improved precision level for manipulating living organisms and biomaterials, [13] and could possibly synergize with 3D lattices, used as boundaries or structural supports. This would help to minimize hydrogel creep and to achieve multi-scale and multi-material scaffolding structures with biomimetic functional gradients of mechanical properties. In contrast, the most precise additive manufacturing technologies, especially two-photon polymerization, which enables interactions even at single cellular level, [14] are not still adequate in terms of throughput and the overall building volume is normally limited to less than 1 mm 3. Furthermore, the materials used by most industrial AMTs, especially those relying on photopolymerization, are normally inadequate for implantation and, consequently, the achieved cell culture systems are limited to performing in vitro studies. In some cases, the use of carbon coatings (i.e., diamond-like carbon) upon laser stereolithography microsystems [15] or the use of carbon fibers knitted to 3D-printed
Background: Metallic nanorods are promising agents for a wide range of biomedical applications. In this study, we developed an optical hyperthermia method capable of inducing in vitro death of glioblastoma cells. Methods: The procedure used was based on irradiation of gold nanorods with a continuous wave laser. This kind of nanoparticle converts absorbed light into localized heat within a short period of time due to the surface plasmon resonance effect. The effectiveness of the method was determined by measuring changes in cell viability after laser irradiation of glioblastoma cells in the presence of gold nanorods. Results: Laser irradiation in the presence of gold nanorods induced a significant decrease in cell viability, while no decrease in cell viability was observed with laser irradiation or incubation with gold nanorods alone. The mechanism of cell death mediated by gold nanorods during photothermal ablation was analyzed, indicating that treatment compromised the integrity of the cell membrane instead of initiating the process of programmed cell death. Conclusion:The use of gold nanorods in hyperthermal therapies is very effective in eliminating glioblastoma cells, and therefore represents an important area of research for therapeutic development.
Several computational models, both continuum and discrete, allow for the simulation of collective cell behaviors in connection with challenges linked to disease modeling and understanding. Normally, discrete cell modelling employs quasi-infinite or boundary-less 2D lattices, hence modeling collective cell behaviors in Petri dish-like environments. The advent of lab- and organ-on-a-chip devices proves that the information obtained from 2D cell cultures, upon Petri dishes, differs importantly from the results obtained in more biomimetic micro-fluidic environments, made of interconnected chambers and channels. However, discrete cell modelling within lab- and organ-on-a-chip devices, to our knowledge, is not yet found in the literature, although it may prove useful for designing and optimizing these types of systems. Consequently, in this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips (and their multi-chamber and multi-channel structures), and the lattices for discrete cell modeling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models. We illustrate the proposal using a quite straightforward cellular automata model, apply it to simulating cells with different growth rates, within a selected set of microsystem designs, and validate it by tuning the growth rates with the support of cell culture experiments and by checking the results with a real microfluidic system.
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