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Journal ArticleDOI: 10.1016/J.JCONREL.2021.02.036

The triad of nanotechnology, cell signalling, and scaffold implantation for the successful repair of damaged organs: An overview on soft-tissue engineering.

04 Mar 2021-Journal of Controlled Release (Elsevier)-Vol. 332, pp 460-492
Abstract: As a milestone in therapeutic fields, tissue engineering has offered an alternative strategy to address unmet clinical needs for the repair and replacement of human damaged organs. The premise of regenerative medicine follows an essential triad of cells, substrates, and physiologically active biomolecules to generate advanced therapeutic methods for tissue repair. Biomedical usages of nanotechnology in regenerative medicine are considerably growing. Dynamic three-dimensional nano-environments can deliver bioactive molecular substrates to accelerate the recovery of damaged tissues by inducing the preservation, proliferation, and differentiation of healthy cells. Nanotechnology provides the possibility to optimize the characteristics of scaffolds and tune their biological functionality (e.g., cellular attachment, electrical conductivity, biocompatibility, and cell-differentiation inducing effect). In addition, nanoscale substances can supply scaffolds via releasing several loaded drugs and triggering cellular proliferation to deliver efficient repair of various organs such as bone, cornea, cartilage, and the heart. Overall, the nature of damaged tissues, as well as scaffolds' composition, porous structure, degradability, and biocompatibility are determinant factors for successful tissue engineering. This review has addressed the most recent advances in the tissue engineering of various organs with a focus on the applications of nanomaterials in this field.

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8 results found


Journal ArticleDOI: 10.1016/J.JCONREL.2021.04.003
Abstract: The tissue engineering of hard organs and tissues containing cartilage, teeth, and bones is a widely used and rapidly progressing field. One of the main features of hard organs and tissues is the mineralization of their extracellular matrices (ECM) to enable them to withstand pressure and weight. Recently, a variety of printing strategies have been developed to facilitate hard organ and tissue regeneration. Fundamentals in three-dimensional (3D) printing techniques are rapid prototyping, additive manufacturing, and layered built-up and solid-free construction. This strategy promises to replicate the multifaceted architecture of natural tissues. Nowadays, 3D bioprinting techniques have proved their potential applications in tissue engineering to construct transplantable hard organs/tissues including bone and cartilage. Though, 3D bioprinting methods still have some uncertainties to fabricate 3D hard organs/tissues. In the present review, most advanced technical improvements, experiments, and future outlooks of hard tissue engineering are discussed, as well as their relevant additive manufacturing techniques.

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Topics: 3D bioprinting (64%)

4 Citations


Journal ArticleDOI: 10.1016/J.IJPHARM.2021.120733
Abstract: This study was aimed to investigate the effects of the Poly-e-Caprolactone/Gelatin nanofibers (PCL/GEL NFs) co-encapsulated with TiO2 nanoparticles (nTiO2) and metformin-loaded mesoporous silica nanoparticles (MET@MSNs) on prolonging the in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence and aging FTIR, BET, FE-SEM, and TEM were applied to characterize the fabricated MET@MSNs and electrospun composite NFs The presence of inorganic particles, nTiO2 and MSNs, in the scaffolds improved their mechanical properties and led to a more sustained release of MET with almost the lack of the initial burst release from nTiO2/MET@MSNs-loaded NFs The enhanced adhesion, metabolic activity, and proliferation rate of the hADSCs grown on nTiO2/MET@MSNs-loaded NFs were demonstrated via FE-SEM images, MTT test and PicoGreen assay, respectively, over 28 days of culture Furthermore, the irregular nanofibrillar structures and the impact of sustained release of MET led to a significant upregulation in the mRNA levels of autophagy (Atg-5, Atg-7, Atg-12, and Beclin-1) and stemness (Nanog3, Sox-2, and Oct-4) markers as well as a considerable down-regulation of p16INK4A senescence marker Further, the upregulation of hTERT, enhanced activity of telomerase, and increased telomere length were more pronounced in the hADSCs cultured on nTiO2/MET@MSNs-loaded NFs as compared to other types of NFs Overall, our findings demonstrated the potential of the fabricated nanocomposite platform for counteracting cellular senescence and achieving sufficient quantities of fresh hADSCs with preserved stemness for various stem cell-based regenerative medicine purposes

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3 Citations


Open accessJournal ArticleDOI: 10.1016/J.BIOACTMAT.2021.07.028
Liwei Fu1, Liwei Fu2, Pinxue Li2, Pinxue Li1  +21 moreInstitutions (3)
Abstract: Many recent studies have shown that joint-resident mesenchymal stem cells (MSCs) play a vital role in articular cartilage (AC) in situ regeneration. Specifically, synovium-derived MSCs (SMSCs), which have strong chondrogenic differentiation potential, may be the main driver of cartilage repair. However, both the insufficient number of MSCs and the lack of an ideal regenerative microenvironment in the defect area will seriously affect the regeneration of AC. Tetrahedral framework nucleic acids (tFNAs), notable novel nanomaterials, are considered prospective biological regulators in biomedical engineering. Here, we aimed to explore whether tFNAs have positive effects on AC in situ regeneration and to investigate the related mechanism. The results of in vitro experiments showed that the proliferation and migration of SMSCs were significantly enhanced by tFNAs. In addition, tFNAs, which were added to chondrogenic induction medium, were shown to promote the chondrogenic capacity of SMSCs by increasing the phosphorylation of Smad2/3. In animal models, the injection of tFNAs improved the therapeutic outcome of cartilage defects compared with that of the control treatments without tFNAs. In conclusion, this is the first report to demonstrate that tFNAs can promote the chondrogenic differentiation of SMSCs in vitro and enhance AC regeneration in vivo, indicating that tFNAs may become a promising therapeutic for AC regeneration.

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2 Citations


Open accessJournal ArticleDOI: 10.3390/MA14123149
08 Jun 2021-Materials
Abstract: Tissue engineering (TE) scaffolds have enormous significance for the possibility of regeneration of complex tissue structures or even whole organs. Three-dimensional (3D) printing techniques allow fabricating TE scaffolds, having an extremely complex structure, in a repeatable and precise manner. Moreover, they enable the easy application of computer-assisted methods to TE scaffold design. The latest additive manufacturing techniques open up opportunities not otherwise available. This study aimed to summarize the state-of-art field of 3D printing techniques in applications for tissue engineering with a focus on the latest advancements. The following topics are discussed: systematics of the available 3D printing techniques applied for TE scaffold fabrication; overview of 3D printable biomaterials and advancements in 3D-printing-assisted tissue engineering.

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2 Citations


Journal ArticleDOI: 10.1016/J.JCONREL.2021.06.002
Abstract: Mechano-transduction is the procedure of mechanical stimulus translation via cells, among substrate shear flow, topography, and stiffness into a biochemical answer. TAZ and YAP are transcriptional coactivators which are recognized as relay proteins that promote mechano-transduction within the Hippo pathway. With regard to healthy cells in homeostasis, mechano-transduction regularly restricts proliferation, and TAZ and YAP are totally inactive. During cancer development a YAP/TAZ - stimulating positive response loop is formed between the growing tumor and the stiffening ECM. As tumor developments, local stromal and cancerous cells take advantage of mechanotransduction to enhance proliferation, induce their migratory into remote tissues, and promote chemotherapeutic resistance. As a newly progresses paradigm, nanoparticle-conjunctions (such as magnetic nanoparticles, and graphene derivatives nanoparticles) hold significant promises for remote regulation of cells and their relevant events at molecular scale. Despite outstanding developments in employing nanoparticles for drug targeting studies, the role of nanoparticles on cellular behaviors (proliferation, migration, and differentiation) has still required more evaluations in the field of mechanotherapy. In this paper, the in-depth contribution of mechano-transduction is discussed during tumor progression, and how these consequences can be evaluated in vitro.

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Topics: Mechanotherapy (64%), Hippo signaling pathway (53%), Mechanotransduction (51%) ... read more

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378 results found


Journal ArticleDOI: 10.1016/J.NANTOD.2008.10.014
Lijie Zhang1, Thomas J. Webster1Institutions (1)
01 Feb 2009-Nano Today
Abstract: Summary Tissue engineering and regenerative medicine aim to develop biological substitutes that restore, maintain, or improve damaged tissue and organ functionality While tissue engineering and regenerative medicine have hinted at much promise in the last several decades, significant research is still required to provide exciting alternative materials to finally solve the numerous problems associated with traditional implants Nanotechnology, or the use of nanomaterials (defined as those materials with constituent dimensions less than 100 nm), may have the answers since only these materials can mimic surface properties (including topography, energy, etc) of natural tissues For these reasons, over the last decade, nanomaterials have been highlighted as promising candidates for improving traditional tissue engineering materials Importantly, these efforts have highlighted that nanomaterials exhibit superior cytocompatible, mechanical, electrical, optical, catalytic and magnetic properties compared to conventional (or micron structured) materials These unique properties of nanomaterials have helped to improve various tissue growth over what is achievable today In this review paper, the promise of nanomaterials for bone, cartilage, vascular, neural and bladder tissue engineering applications will be reviewed Moreover, as an important future area of research, the potential risk and toxicity of nanomaterial synthesis and use related to human health are emphasized

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Topics: Regenerative medicine (50%)

887 Citations


Journal ArticleDOI: 10.1021/ACSNANO.5B01179
20 Apr 2015-ACS Nano
Abstract: The exceptional properties of graphene enable applications in electronics, optoelectronics, energy storage, and structural composites. Here we demonstrate a 3D printable graphene (3DG) composite consisting of majority graphene and minority polylactide-co-glycolide, a biocompatible elastomer, 3D-printed from a liquid ink. This ink can be utilized under ambient conditions via extrusion-based 3D printing to create graphene structures with features as small as 100 μm composed of as few as two layers ( 10 cm thick object). The resulting 3DG material is mechanically robust and flexible while retaining electrical conductivities greater than 800 S/m, an order of magnitude increase over previously reported 3D-printed carbon materials. In vitro experiments in simple growth medium, in the absence of neurogenic stimuli, reveal that 3DG supports human mesenchymal stem cell (hMSC) adhesion, viability, proliferation, and neurogenic differentiation with significant upregulation of glial and neuronal genes. This coincides with hMSCs adopting highly elongated morphologies with features similar to axons and presynaptic terminals. In vivo experiments indicate that 3DG has promising biocompatibility over the course of at least 30 days. Surgical tests using a human cadaver nerve model also illustrate that 3DG has exceptional handling characteristics and can be intraoperatively manipulated and applied to fine surgical procedures. With this unique set of properties, combined with ease of fabrication, 3DG could be applied toward the design and fabrication of a wide range of functional electronic, biological, and bioelectronic medical and nonmedical devices.

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Topics: Graphene (51%)

461 Citations


Open accessJournal ArticleDOI: 10.1073/PNAS.1524510113
Xuanyi Ma1, Xin Qu1, Wei Zhu1, Yi-Shuan Li1  +10 moreInstitutions (1)
Abstract: The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

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Topics: 3D bioprinting (61%), Cellular differentiation (54%), Stem cell (53%) ... read more

455 Citations


Open accessJournal ArticleDOI: 10.1038/NMAT4782
01 Mar 2017-Nature Materials
Abstract: Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro, have emerged as a promising alternative. However, current MPS typically lack integrated sensors and their fabrication requires multi-step lithographic processes. Here, we introduce a facile route for fabricating a new class of instrumented cardiac microphysiological devices via multimaterial three-dimensional (3D) printing. Specifically, we designed six functional inks, based on piezo-resistive, high-conductance, and biocompatible soft materials that enable integration of soft strain gauge sensors within micro-architectures that guide the self-assembly of physio-mimetic laminar cardiac tissues. We validated that these embedded sensors provide non-invasive, electronic readouts of tissue contractile stresses inside cell incubator environments. We further applied these devices to study drug responses, as well as the contractile development of human stem cell-derived laminar cardiac tissues over four weeks.

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435 Citations


Journal ArticleDOI: 10.1016/J.BIOMATERIALS.2010.07.045
01 Nov 2010-Biomaterials
Abstract: Blood kinetics and tissue distribution of 20, 80 and 110 nm silver nanoparticles were investigated in rats up to 16 days after intravenous administration once daily for 5 consecutive days Following both single and repeated injection, silver nanoparticles disappeared rapidly from the blood and distributed to all organs evaluated (liver, lungs, spleen, brain, heart, kidneys and testes) regardless of size The 20 nm particles distributed mainly to liver, followed by kidneys and spleen, whereas the larger particles distributed mainly to spleen followed by liver and lung In the other organs evaluated, no major differences between the sizes were observed Size-dependent tissue distribution suggests size-dependent toxicity and health risks Repeated administration resulted in accumulation in liver, lung and spleen, indicating that these organs may be potential target organs for toxicity after repeated exposure A physiologically based pharmacokinetic (PBPK) model for nanoparticles which describes the kinetics of silver nanoparticles was developed Model parameter values were estimated by fitting to data No clear relation between parameter values and corresponding particle diameters became apparent

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Topics: Silver nanoparticle (52%)

399 Citations


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