Adding a large amount of light elements such as aluminum to steels is not a new concept recalling that several Fe-Al-Mn-C alloys were patented in 1950s for replacement of nickel or chromium in ...corrosion resistance steels. However, the so-called lightweight steels or low-density steels were revisited recently, which is driven by demands from the industry where steel has served as a major structural material. Strengthening without loss of ductility has been a triumph in steel research, but lowering the density of steel by mixing with light elements will be another prospect that may support the competitiveness against emerging alternatives such as magnesium alloys. In this paper, we review recent studies on lightweight steels, emphasizing the concept of alloy design for microstructures and mechanical properties. The influence of alloying elements on the phase constituents, mechanical properties and the change of density is critically reviewed. Deformation mechanisms of various lightweight steels are discussed as well. This paper provides a reason why the success of lightweight steels is strongly dependent on scientific achievements even though alloy development is closely related to industrial applications. Finally, we summarize some of the main directions for future investigations necessary for vitalizing this field of interest.
Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to ...achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.
3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations. In skin tissue ...engineering, a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials, which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment. In this study, we investigated the capability of skin-derived extracellular matrix (S-dECM) bioink for 3D cell printing-based skin tissue engineering. S-dECM was for the first time formulated as a printable material and retained the major ECM compositions of skin as well as favorable growth factors and cytokines. This bioink was used to print a full thickness 3D human skin model. The matured 3D cell-printed skin tissue using S-dECM bioink was stabilized with minimal shrinkage, whereas the collagen-based skin tissue was significantly contracted during in vitro tissue culture. This physical stabilization and the tissue-specific microenvironment from our bioink improved epidermal organization, dermal ECM secretion, and barrier function. We further used this bioink to print 3D pre-vascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPCs)-laden 3D-printed skin patch together with adipose-derived stem cells (ASCs) accelerates wound closure, re-epithelization, and neovascularization as well as blood flow. We envision that the results of this paper can provide an insightful step towards the next generation source for bioink manufacturing.
As the main precursor of cardiovascular diseases, atherosclerosis is a complex inflammatory disorder that preferentially occurs in stenotic, curved, and branched arterial regions. Although various in ...vitro models are established to understand its pathology, reconstructing the native atherosclerotic environment that involves both co‐cultured cells and local turbulent flow singling remains challenging. This study develops an arterial construct via in‐bath coaxial cell printing that not only facilitates the direct fabrication of three‐layered conduits with tunable geometry and dimensions but also maintains structural stability. Functional vascular tissues, which respond to various stimulations that induce endothelial dysfunction, are rapidly generated in the constructed models. The presence of multiple vascular tissues under stenotic and tortuous turbulent flows allows the recapitulation of hallmark events in early atherosclerosis under physiological conditions. Furthermore, the fabricated models are utilized to investigate the individual and synergistic functions of cell co‐culture and local turbulent flows in regulating atherosclerotic initiation, as well as the dose‐dependent therapeutic effect of atorvastatin. These outcomes suggest that the constructed atherosclerotic model via a novel fabrication strategy is a promising platform to elucidate the pathophysiology of atherosclerosis and seek effective drugs and therapies.
An advanced in vitro atherosclerosis model that enables the co‐culture of multiple vascular cells under local turbulent flows is developed from geometry‐tunable arterial constructs engineered by a novel in‐bath coaxial cell printing strategy. This platform recapitulates the hallmark events in early atherosclerosis and shows great potential for understanding the atherosclerotic pathophysiology and evaluating drug efficacy.
Biomaterials-based biofabrication methods have gained much attention in recent years. Among them, 3D cell printing is a pioneering technology to facilitate the recapitulation of unique features of ...complex human tissues and organs with high process flexibility and versatility. Bioinks, combinations of printable hydrogel and cells, can be utilized to create 3D cell-printed constructs. The bioactive cues of bioinks directly trigger cells to induce tissue morphogenesis. Among the various printable hydrogels, the tissue- and organ-specific decellularized extracellular matrix (dECM) can exert synergistic effects in supporting various cells at any component by facilitating specific physiological properties. In this review, we aim to discuss a new paradigm of dECM-based bioinks able to recapitulate the inherent microenvironmental niche in 3D cell-printed constructs. This review can serve as a toolbox for biomedical engineers who want to understand the beneficial characteristics of the dECM-based bioinks and a basic set of fundamental criteria for printing functional human tissues and organs.
The liver is an important organ and plays major roles in the human body. Because of the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing ...liver alternatives and liver in vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation. However, a great deal of work in developing biomaterials optimized for 3D cell printing-based liver tissue engineering remains. Therefore, in this work, we developed a liver decellularized extracellular matrix (dECM) bioink for 3D cell printing applications and evaluated its characteristics. The liver dECM bioink retained the major ECM components of the liver while cellular components were effectively removed and further exhibited suitable and adjustable properties for 3D cell printing. We further studied printing parameters with the liver dECM bioink to verify the versatility and fidelity of the printing process. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to those of commercial collagen bioink were also evaluated, and the liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. Consequently, the results demonstrate that the proposed liver dECM bioink is a promising bioink candidate for 3D cell printing-based liver tissue engineering.
Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in ...cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.
The extracellular matrix of vascular tissue is formulated as a bioink to engineer a bioinspired blood vessel using the 3D coaxial cell printing technique. Carrying progenitor cells and proangiogenic drugs, the transplanted construct exhibits remarkable therapeutic efficacy for ischemic diseases.
Abstract
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective ...clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes
WNT3
transcription, leading to activation of the WNT/β-catenin pathway in
Apc
Min/+
/Lgr5
EGFP
mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
We highlight the recent advance in strong transformation-induced plasticity (TRIP) steels, which have higher alloying contents compared to the conventional TRIP steels for achieving tensile strength ...higher than 1GPa. Given that the extraordinary strength-elongation balance is led by the characteristic mixture of coarse and submicron-sized grains of ferrite and austenite, diverse strategies of materials design to obtain unprecedented properties are reviewed. Challenges to achieve the vital engineering parameters other than tensile properties are discussed as well, which should be resolved to secure competitiveness over other emerging structural alternatives.
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Regenerative medicine is targeted to improve, restore or replace damaged tissues or organs using a combination of cells, materials and growth factors. Both tissue engineering and developmental ...biology currently deal with the process of tissue self-assembly and extracellular matrix (ECM) deposition. In this investigation, additive manufacturing (AM) with a multihead deposition system (MHDS) was used to fabricate three-dimensional (3D) cell-printed scaffolds using layer-by-layer (LBL) deposition of polycaprolactone (PCL) and chondrocyte cell-encapsulated alginate hydrogel. Appropriate cell dispensing conditions and optimum alginate concentrations for maintaining cell viability were determined. In vitro cell-based biochemical assays were performed to determine glycosaminoglycans (GAGs), DNA and total collagen contents from different PCL-alginate gel constructs. PCL-alginate gels containing transforming growth factor-β (TGFβ) showed higher ECM formation. The 3D cell-printed scaffolds of PCL-alginate gel were implanted in the dorsal subcutaneous spaces of female nude mice. Histochemical Alcian blue and haematoxylin and eosin (H&E) staining and immunohistochemical (type II collagen) analyses of the retrieved implants after 4 weeks revealed enhanced cartilage tissue and type II collagen fibril formation in the PCL-alginate gel (+TGFβ) hybrid scaffold. In conclusion, we present an innovative cell-printed scaffold for cartilage regeneration fabricated by an advanced bioprinting technology.
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