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Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer.
Highlights: • A role of the basolateral plasma membrane in targeting of AQP2 to the apical membrane is shown. • The levels of basolateral membrane cholesterol are involved in this mechanism. • Cholesterol depletion increases AQP2 ubiquitylation but prevents AQP2 phosphorylation. • Effects of cholesterol depletion on AQP2 are independent of changes in intracellular cAMP. • Results are important for understanding basic principles of membrane protein trafficking. Apical plasma membrane accumulation of the water channel Aquaporin-2 (AQP2) in kidney collecting duct principal cells is critical for body water homeostasis. Posttranslational modification (PTM) of AQP2 is important for regulating AQP2 trafficking. The aim of this study was to determine the role of cholesterol in regulation of AQP2 PTM and in apical plasma membrane targeting of AQP2. Cholesterol depletion from the basolateral plasma membrane of a collecting duct cell line (mpkCCD14) using methyl-beta-cyclodextrin (MBCD) increased AQP2 ubiquitylation. Forskolin, cAMP or dDAVP-mediated AQP2 phosphorylation at Ser269 (pS269-AQP2) was prevented by cholesterol depletion from the basolateral membrane. None of these effects on pS269-AQP2 were observed when cholesterol was depleted from the apical side of cells, or when MBCD was applied subsequent to dDAVP stimulation. Basolateral, but not apical, MBCD application prevented cAMP-induced apical plasma membrane accumulation of AQP2. These studies indicate that manipulation of the cholesterol content of the basolateral plasma membrane interferes with AQP2 PTM and subsequently regulated apical plasma membrane targeting of AQP2.
Highlights: • Intracellular cholesterol positively regulates temozolomide-induced glioma apoptosis. • DR5-caspase-8 axis is essential for enhancement of glioma apoptosis by cholesterol. • HMG-CoA reductase inhibitors suppress temozolomide-induced glioma apoptosis. • Intracellular cholesterol loading overcomes temozolomide resistance of glioma cells. Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism.
Highlights: • Kinetic regime of aggregation of UV-irradiated glyceraldehyde-3-phosphate dehydrogenase at 37°C has been established. • The rate of stage of aggregate growth is limited by monomolecular structural reorganization of the irradiated protein. • 2-Hydroxypropyl-b-cyclodextrin decelerates stage of structural reorganization of irradiated enzyme and nucleation stage. The study of the kinetics of aggregation of UV-irradiated proteins has attracted considerable interest, since test systems based on aggregation of proteins denatured by UV radiation can be used for screening of the natural and artificial agents possessing chaperone-like activity (anti-aggregation activity). To provide the proper interpretation of the effects caused by the agents under study, the kinetic mechanism of the aggregation process should be established. In the present work the kinetic data on aggregation of UV-irradiated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from rabbit skeletal muscle at 37 °C (O.I. Maloletkina et al. Biophys. Chem. 163–164 (2012) 11–20) have been analyzed. It has been shown that the stage of aggregate growth follows the first-order kinetics and the experimentally measured rate constant of the first order corresponds to heat-induced structural reorganization of UV-irradiated GAPDH containing concealed damage.
Highlights: • Multicomponent reaction (MCR) is a productive and economical method for the synthesis of antitumor compounds by connecting functional moieties. • A series of indole substituted dihydropyrido[2,3-d]pyrimidines were synthesized by MCR. • 4p exhibits antitumor activity both in vitro and in vivo via inhibiting AKT and ERK1/2 pathways on hepatocellular carcinoma. Development of an effective and safe anti-cancer drug is an urgent request for hepatocellular carcinoma (HCC). In this study, we synthesized a series of novel indole substituted dihydropyrido[2,3-d]pyrimidines through the multicomponent reactions to connect pyrido[2,3-d]pyrimidine and indole moities via an one-pot three-component reaction of 3-cyanoacetyl indoles 1, various aromatic aldehyde 2, and 2,6-diaminopyrimidin-4(3H)-one 3. Subsequently, we screened their cytotoxicity via CCK-8 assay in HepG2 cells, a human hepatoma cell line and chose compound 4p that showed the lowest dosage of IC50 to study the antitumor activities to HCC. Interestingly, 4p significantly induced the cell cycle arrest and apoptosis of HepG2 via targeting AKT and ERK1/2 signaling pathways in vitro. To improve the solubility of compound 4p, we hosted this compound into the substituted glucopyranose ring of (2-Hydroxypropyl)-β-cyclodextrin (HBC), a cosolvent approved by FDA with the help of ultrasonication and heating. Finally, we showed that oral administration of HBC-hosted 4p effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice in subcutaneously xenografted model. These results suggest that multicomponent reactions connecting pyrido[2,3-d]pyrimidine and indole moities is a productive and economical method for the synthesis of anticancer compound, and oral administration of HBC-hosted 4p is an effective and safe agents for treatment of HCC, whose clinical application potency warrant further studies.
Highlights: • Membranes of cultured insect cells were studied with spin label EPR. • Two kinds of spin labels (SL) with different chemical affinity were used. • EPR of SL chemically akin to cholesterol indicates its uneven distribution in intact cells. • Evidence of cholesterol enriched nanodomains in intact cell membranes. • Cholesterol depletion erases the EPR evidence of cell membrane domains. Different spin labels were incorporated to the membranes of cultured insect UFL-AG-286 cells in order to characterize their physical properties by Electron Paramagnetic Resonance spectroscopy (EPR). The spectrum of the spin label 12-SASL incorporated to cell membranes was similar as those obtained in membrane model systems composed of eggPC/cholesterol. However, the spectrum of the spin label CSL, chemically related to cholesterol, was drastically different in the two systems. Interestingly, when cell cholesterol content was reduced using methyl beta cyclodextrin, an EPR spectrum similar to those of model membranes was obtained. The analysis of these experiments suggests the existence of cholesterol rich regions in UFL-AG-286 cell membranes.
Graphical abstract: - Highlights: • Mercapto groups were grafted to chitosan molecule by a reactive amine reduction. • Functional polymer with well-defined monomer units controls AuNPs assembly. • Assembled morphologies depend on the ratio of AuNPs to thiolate groups. • Microcubes with side length of ∼20 μm was synthesized through a dialysis step. • A edge-to-middle growth mechanism of gold microcubes was observed. - Abstract: The L-cysteine molecules were successfully grafted to the 2-amino group of chitosan by a reactive amine reduction, and the as-synthesized thiolated chitosan (TC) molecules were used as the templates to direct the self-assembly of gold nanoparticles and induce the transformation of these assemblies to gold microcubes through a deep-going dialysis. We found that the ratio of gold nanoparticles to TC molecules could greatly affect the shape of the assembled clusters. Different stages of these clusters and microstructures during the dialysis process were characterized by scanning electron microscope (SEM), and the microcubes with average side length of about 20 μm were successfully synthesized. According to the morphology evolution of the assembly, it could be concluded that the microcubes were formed from external to internal. The SERS area mapping images of microcubes and some clusters were also collected to study the formation mechanism of gold microcubes. Our work demonstrates a simple and highly effective way to assemble gold nanoparticles into microcubes with unique properties.
Highlights: • Cooperative integration of magnetic cores and chitosan layers. • Efficient and durable catalyst for the oxidation of ethylbenzene to acetophenone. • Exceptional results of 82.5% EB conversion and 80.4% AP selectivity. • Magnetic recoverable catalyst with excellent reusability even after 10 times run. - Abstract: The preparation of Co(II) supported magnetic heterogeneous catalyst, i.e. Fe{sub 3}O{sub 4}@SiO{sub 2}–NH{sub 2}@CS–Co, and its efficient and selective catalytic properties toward the oxidation of ethylbenzene to acetophenone are presented. The materials were characterized by various physicochemical techniques such as scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, vibrating sample magnetometer, elemental analysis, inductively coupled plasma-atomic emission spectrometer and X-ray photoelectron spectroscopy, etc. The reaction conditions were thoroughly investigated and highly improved catalytic performance (82.5% conversion of ethylbenzene and 80.1% selectivity to acetophenone) was gained under more mild reaction conditions of lower temperature (70 °C), shorter reaction period (60 min) and cheaper and greener oxygen source (H{sub 2}O{sub 2}). More importantly, it could be reused successively at least 10 times when more than 80% of its catalytic activity maintained.
Highlights: • Chitosan-based grapefruit seed extract (GFSE) films were solution casted. • GFSE was uniformly dispersed within all chitosan film matrices. • All chitosan-based composite films showed remarkable transparency. • Increasing amounts of GFSE incorporated increased the elongation at break of films. • Chitosan-based GFSE composite films inhibited the proliferation of fungal growth. - Abstract: Chitosan-based composite films with different amounts of grapefruit seed extract (GFSE) (0.5, 1.0 and 1.5% v/v) were fabricated via solution casting technique. Experimental results showed that GFSE was uniformly dispersed within all chitosan film matrices. The presence of GFSE made the films more amorphous and tensile strength decreased, while elongation at break values increased as GFSE content increased. Results from the measurement of light transmission revealed that increasing amounts of GFSE (from 0.5 to 1.5% v/v) did not affect transparency of the films. Furthermore, packaging of bread samples with chitosan-based GFSE composite films inhibited the proliferation of fungal growth as compared to control samples. Hence, chitosan-based GFSE composite films have the potential to be a useful material in the area of food technology.
Highlights: • Microwave-assisted synthesis of rotaxane based on anthracene and β-cyclodextrin. • Morphological and optical characterization of thin solid film. • Elaboration of impedimetric gold/rotaxane sensor. • Investigation of the membrane sensitivity towards Hg{sup 2+}, Cu{sup 2+} and Pb{sup 2+} cations. - Abstract: An impedimetric sensor based on a new semi-conducting rotaxane has been described for detection of toxic cations. The rotaxane, consists on a π-conjugated material encapsulated into β-cyclodextrin (β-CD); it has been synthesized via the Williamson reaction under microwaves irradiation. The supramolecular structure of the compound was confirmed by NMR and FT-IR spectroscopies. A thin solid film of the rotaxane was deposited by spin-coating to develop a new electrochemical sensor. The morphological properties of the organic membrane were evaluated using contact angle measurements and atomic force microscopy. The gold/rotaxane/solution interfaces were investigated by electrochemical impedance spectroscopy and the obtained data were fitted using an equivalent electrical circuit. The response of the gold/rotaxane membrane towards Hg{sup 2+}, Cu{sup 2+} and Pb{sup 2+} cations was studied and the results showed a good sensitivity to the mercury cations.
Highlights: • HTCC/PVA blend films were prepared through a simple mixing method. • The blend films had greater elongation at break and good optical transmittance. • The blend films had low oxygen permeability and water vapor permeability. • The films had good activity against Escherichia coli and Staphylococcus aureus. - Abstract: Blend films from poly (vinyl alcohol) (PVA) containing N-(2-hydroxy) propyl-3-trimethyl ammonium chloride chitosan (HTCC) were prepared via a simple mixing and casting method. The films were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction measurements (XRD), scanning electron microscopy and ultraviolet-visible measurements (UV–vis). The effects of HTCC amount on mechanical properties, oxygen permeability, water vapor permeation, and antibacterial properties against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) of the films were investigated. FTIR and XRD analysis show that HTCC and PVA in the blend films interacted by hydrogen bonding. SEM and UV–vis analysis reveal the good compatibility between HTCC and PVA. Compared with pure PVA film, the blend films had greater elongation at break, lower water permeability, and higher antibacterial activity. The HTCC addition decreased the tensile strength and the light transmittance. The results suggest that HTCC/PVA blend films have a potential as packaging materials.
Highlights: • Nano magnetite–chitosan films were prepared by casting method. • The efficiency of the prepared films for removing heavy metals was investigated. • The adsorption mechanism was studied using different isotherm and kinetic models. • Films reuse and metals recovery were studied. - Abstract: Nano magnetite chitosan (NMag–CS) film was prepared and characterized with different analytical methods. X-ray diffraction (XRD) patterns confirmed the formation of a pure magnetite structure and NMag–CS nanocomposite. TEM image of the film, revealed the uniform dispersion of magnetite nanoparticles inside chitosan matrix. The adsorption properties of the prepared film for copper, lead, cadmium, chromium and nickel metal ions were evaluated. Different factors affecting the uptake behavior by the composite films such as time, initial pH and film dose were investigated. The adsorption equilibrium attained using 2 g/L of the film after 120 min of reaction. The equilibrium data were analyzed using Langmuir and Freundlich models. The adsorption kinetics followed the mechanism of the pseudo-second-order equation for all metals. The metals regenerated from films with an efficiency greater than 95% using 0.1 M ethylene diamine tetra acetic acid (EDTA) and films were successfully reused for adsorption.
Background: : In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. Objective: : To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. Methods: : HaCaT cells were treated for 24 h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Results: : Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Conclusion: : Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds. - Highlights: • Hypoxia impairs MMP9/TIMP1 and MMP2/TIMP2 balances in HaCaT human keratinocytes. • Chitosan-shelled oxygen-loaded nanodroplets (OLNs) are internalised by HaCaT cells. • OLNs are not toxic to HaCaT cells. • OLNs effectively counteract hypoxia effects on MMP/TIMP balances in HaCaT cells. • OLNs appear as promising and cost-effective therapeutic tools for hypoxic wounds.
Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP2A/MMP-2 induced PCB153-induced dysfunction of occludin. • Disrupted lipid rafts modulated PCB153-induced increase of permeability. • Lipid rafts act as a signaling platform for PCB153-induced dysfunction of occludin.
In chronic wounds, hypoxia seriously undermines tissue repair processes by altering the balances between pro-angiogenic proteolytic enzymes (matrix metalloproteinases, MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) released from surrounding cells. Recently, we have shown that in human monocytes hypoxia reduces MMP-9 and increases TIMP-1 without affecting TIMP-2 secretion, whereas in human keratinocytes it reduces MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. Provided that the phenotype of the cellular environment is better understood, chronic wounds might be targeted by new oxygenating compounds such as chitosan- or dextran-shelled and 2H,3H-decafluoropentane-cored oxygen-loaded nanodroplets (OLNs). Here, we investigated the effects of hypoxia and dextran-shelled OLNs on the pro-angiogenic phenotype and behavior of human dermal microvascular endothelium (HMEC-1 cell line), another cell population playing key roles during wound healing. Normoxic HMEC-1 constitutively released MMP-2, TIMP-1 and TIMP-2 proteins, but not MMP-9. Hypoxia enhanced MMP-2 and reduced TIMP-1 secretion, without affecting TIMP-2 levels, and compromised cell ability to migrate and invade the extracellular matrix. When taken up by HMEC-1, nontoxic OLNs abrogated the effects of hypoxia, restoring normoxic MMP/TIMP levels and promoting cell migration, matrix invasion, and formation of microvessels. These effects were specifically dependent on time-sustained oxygen diffusion from OLN core, since they were not achieved by oxygen-free nanodroplets or oxygen-saturated solution. Collectively, these data provide new information on the effects of hypoxia on dermal endothelium and support the hypothesis that OLNs might be used as effective adjuvant tools to promote chronic wound healing processes. - Highlights: • Hypoxia enhances MMP-2 and reduces TIMP-1 secretion by dermal HMEC-1 cell line. • Hypoxia compromises migration and matrix invasion abilities of HMEC-1. • Nontoxic dextran-shelled oxygen-loaded nanodroplets (OLNs) are uptaken by HMEC-1. • Dextran-shelled OLNs abrogate hypoxia effects on HMEC-1 pro-angiogenic phenotype. • Dextran-shelled OLNs abrogate hypoxia effects on HMEC-1 pro-angiogenic behavior.
Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5 mg/kg body weight compared to free Curcumin at 35 mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, β-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. - Highlights: • Cardiomyocyte targeted Curcumin/CMC-peptide increases bioavailability of the drug. • Curcumin nanoparticle regresses cardiac hypertrophy by reducing myocyte apoptosis. • Targeted Curcumin shows higher efficacy over free Curcumin to regress hypertrophy. • Curcumin modulates p300-HAT axis to facilitate p53 degradation.
Cation trapping in acidic cell compartments determines an antiproliferative effect that has a potential interest in oncology, as shown by clinical data and trials involving chloroquine and hydroxychloroquine. To further characterize the mechanism of this effect, we studied a series of 6 substituted triethylamine (s-Et{sub 3}N) drugs that encompasses a wide range of liposolubility (amiodarone, quinacrine, chloroquine, hydroxychloroquine, lidocaine, and procainamide). Three tumor cell lines and primary human endothelial cells were exploited in proliferation assays (48 h, cell counts). Accumulation of the autophagic effector LC3 II and the apoptotic marker cleaved PARP1 (immunoblots), cytotoxicity, cell cycle analysis and endocytic function were further tested in the p53-null histiocytic lymphoma U937 line. A profound and desynchronized antiproliferative effect was observed in response to all s-Et{sub 3}Ns with essentially no cell type specificity. Predictors of s-Et{sub 3}N potency were liposolubility and the acute accumulation of the autophagic effector LC3 II (6 h-treatments). For each s-Et{sub 3}N, there was an antiproliferative concentration range where cytotoxicity and apoptosis were not triggered in U937 cells (24–48 h-treatments). Quinacrine was the most potent cytostatic drug (1–5 μM). Co-treatment of cells with inhibitors of cholesterol, β-cyclodextrin or lovastatin, partially reversed the antiproliferative effect of each s-Et{sub 3}N. The cytopathology induced by cationic drug accumulation includes a cytostatic effect. Its intensity is cell type- and p53-independent, but predicted by the inhibition of autophagic flux and by the liposolubility of individual drugs and alleviated by cholesterol ablation. The superiority of quinacrine, biomarker value of LC3 II and antagonism by a statin may be clinically relevant. - Highlights: • Cation trapping in acidic cell compartments induces a cytostatic effect. • A series of substituted triethylamines has been studied in 4 cell types. • Cytostatic potency is predicted by lipophilicity and autophagic flux inhibition. • β-Cyclodextrin or lovastatin co-treatment reverses the antiproliferative effect.
The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.