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In the last decades, biomedical research has significantly boomed in the academia and industrial sectors, and it is expected to continue to grow at a rapid pace in the future. An in-depth analysis of such growth is not trivial, given the intrinsic multidisciplinary nature of biomedical research. Nevertheless, technological advances are among the main factors which have enabled such progress. In this review, we discuss the contribution of two state-of-the-art technologies–namely biofabrication and organ-on-a-chip–in a selection of biomedical research areas. We start by providing an overview of these technologies and their capacities in fabricating advanced in vitro tissue/organ models. We then analyze their impact on addressing a range of current biomedical challenges. Ultimately, we speculate about their future developments by integrating these technologies with other cutting-edge research fields such as artificial intelligence and big data analysis.

This paper reports on a novel approach for the fabrication of composite multilayered bioink-nanofibers construct. This work achieves this by using a hands-free 3D (bio)printing integrated touch-spinning approach. Additionally, this work investigates the interaction of fibroblasts in different bioinks with the highly aligned touch-spun nanofibers. This work conducts a comprehensive characterization of the rheological properties of the inks, starting with low-strain oscillatory rheology to analyze the viscoelastic behavior, when the material structure remains intact. Moreover, this work performs amplitude sweeps to investigate the stability of the inks under large deformations, rotational rheology to examine the shear thinning profile, and a three-step creep experiment to study time-dependent rheological behavior. The obtained rheological results are correlated to visual observation of the flow behavior of inks. These behaviors span from an ink with zero-shear viscosity, very weak shear thinning, and no thixotropic behavior to inks exhibiting flow stress, pronounced shear thinning, and thixotropy. It is demonstrated that inks have an essential effect on cell behavior. While all bioinks allow a preferred directionality of the fibroblasts along the fiber direction, cells tend to form aggregates in bioinks with higher viscosity, and a considerable number of agglomerates are observed in the presence of laponite-RD., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Cardiovascular disease remains the leading cause of mortality worldwide. The inability of cardiac tissue to regenerate after an infarction results in scar tissue formation, leading to cardiac dysfunction. Therefore, cardiac repair has always been a popular research topic. Recent advances in tissue engineering and regenerative medicine offer promising solutions combining stem cells and biomaterials to construct tissue substitutes that could have functions similar to healthy cardiac tissue. Among these biomaterials, plant-derived biomaterials show great promise in supporting cell growth due to their inherent biocompatibility, biodegradability, and mechanical stability. More importantly, plant-derived materials have reduced immunogenic properties compared to popular animal-derived materials (e.g., collagen and gelatin). In addition, they also offer improved wettability compared to synthetic materials. To date, limited literature is available to systemically summarize the progression of plant-derived biomaterials in cardiac tissue repair. Herein, this paper highlights the most common plant-derived biomaterials from both land and marine plants. The beneficial properties of these materials for tissue repair are further discussed. More importantly, the applications of plant-derived biomaterials in cardiac tissue engineering, including tissue-engineered scaffolds, bioink in 3D biofabrication, delivery vehicles, and bioactive molecules, are also summarized using the latest preclinical and clinical examples., (© 2023 Wiley-VCH GmbH.)

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue. Three-dimensional (3D) printing offers a method of fabricating complex anatomical features of clinically relevant sizes. However, the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging. This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions. The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional (2D). The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices, which were arrayed. These 2D slices with each layer of a defined pattern were laser cut, and then successfully assembled with varying thicknesses of 100 μm or 200 μm. It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions, where the clinically relevant sizes ranging from a simple cube of 20 mm dimension, to a more complex, 50 mm-tall human ears were created. In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure. The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice, where a range of hole diameters from 200 μm to 500 μm were laser cut in an array where cell confluence values of at least 85% were found at three weeks. Cells were also seeded onto a simpler stacked construct, albeit made with micromachined poly fibre mesh, where cells can be found to migrate through the stack better with collagen as bioadhesives. This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.

Biofabrication of tissue models that closely mimic the tumor microenvironment is necessary for high-throughput anticancer therapeutics. Extrusion-based bioprinting of heterogeneous cell-laden hydrogels has shown promise in advancing rapid artificial tissue development. A major bottleneck limiting the rapid production of physiologically relevant tissue models is the current limitation in effectively printing large populations of cells. However, by significantly increasing hydrogel cell-seeding densities, the time required to produce tissues could be effectively reduced. Here, we explore the effects of increasing cell seeding densities on the viscoelastic properties, printability, and cell viability of two different alginate-gelatin hydrogel compositions. Rheological analysis of hydrogels of varying cell seeding densities reveals an inverse relationship between cell concentration and zero-shear viscosity. We also observe that as cell seeding densities increases, the storage moduli decrease, thus lowering the required printing pressures for gel extrusion. We also observe that increasing cell concentration can negatively impact the structural properties of the extruded material by increasing post-print line spreading. We find that hydrogels composed of higher molecular weight alginates and the highest cell-seeding densities (107 cells/mL) yield higher cell viability (>80%) and structural uniformity after printing. The optimized printing parameters determined for the alginate-gelatin bioinks explored may aid in the future rapid fabrication of functional tissue models for therapeutic screening. [ABSTRACT FROM AUTHOR]

Steroid-associated osteonecrosis (SAON) is a chronic disease that leads to the destruction and collapse of bone near the joint that is subjected to weight bearing, ultimately resulting in a loss of hip and knee function. Zn2+ ions, as an essential trace element, have functional roles in improving the immunophysiological cellular environment, accelerating bone regeneration, and inhibiting biofilm formation. In this study, we reconstruct SAON lesions with a three-dimensional (3D)-a printed composite made of poly (epsilon-caprolactone) (PCL) and nanoparticulate Willemite (npW). Rabbit bone marrow stem cells were used to evaluate the cytocompatibility and osteogenic differentiation capability of the PCL/npW composite scaffolds. The 2-month bone regeneration was assessed by a Micro-computed tomography (micro-CT) scan and the expression of bone regeneration proteins by Western blot. Compared with the neat PCL group, PCL/npW scaffolds exhibited significantly increased cytocompatibility and osteogenic activity. This finding reveals a new concept for the design of a 3D-printed PCL/npW composite-based bone substitute for the early treatment of osteonecrosis defects. [ABSTRACT FROM AUTHOR]

Additive manufacturing via layer-by-layer adhesive bonding holds much promise for scalable manufacturing of tissue-like constructs, specifically scaffolds with integrated vascular networks for tissue engineering applications. However, there remains a lack of effective adhesives capable of composite layer fusion without affecting the integrity of patterned features. Here, the use of silicon carbide is introduced as an effective adhesive to achieve strong bonding (0.39 ± 0.03 kPa) between hybrid hydrogel films composed of alginate and collagen. The techniques have allowed us to fabricate multilayered, heterogeneous constructs with embedded high-resolution microchannels (150 µm-1 mm) that are precisely interspaced (500-600 µm). Hydrogel layers are effectively bonded with silicon carbide nanoparticles without blocking the hollow microchannels and high cell viability (90.61 ± 3.28%) is maintained within the scaffold. Nanosilica is also tested and found to cause clogging of smaller microchannels when used for interlayer bonding, but is successfully used to attach synthetic polymers (e.g., Tygon) to the hydrogels (32.5 ± 2.12 mN bond strength). This allows us to form inlet and outlet interconnections to the gel constructs. This ability to integrate hollow channel networks into bulk soft material structures for perfusion can be useful in 3D tissue engineering applications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)