Hydrogels are widely used as scaffold in tissue engineering field because of their ability to mimic the cellular microenvironment. However, mimicking a completely natural cellular environment is ...complicated due to the differences in various physical and chemical properties of cellular environments. Recently, gradient hydrogels provide excellent heterogeneous environment to mimic the different cellular microenvironments. To create hydrogels with an anisotropic distribution, gradient hydrogels have been widely developed by adopting several gradient generation techniques. Herein, the various gradient hydrogel fabrication techniques, including dual syringe pump systems, microfluidic device, photolithography, diffusion, and bio‐printing are summarized. As the effects of gradient 3D hydrogels with stems have been reviewed elsewhere, this review focuses principally on gradient hydrogel fabrication for multi‐model tissue regeneration. This review provides new insights into the key points for fabrication of gradient hydrogels for multi‐model tissue regeneration.
Gradient formation in hydrogels is a promising strategy for accessing complete imitation of the natural microcellular or tissue environments. Herein, this review summarizes representative strategies for fabrication of gradient hydrogels and their applications in the field of tissue engineering.
Poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation is widely used to prepare coacervate particles by electrostatic complexation with an anionic heparin (HEP) in aqueous environments, for ...controlled release of therapeutic proteins. However, coacervate complexes aggregate randomly due to particle–particle charge interactions. Herein, a new term “coacersome” is introduced to represent a stable polyplex formed by complexation of mPEGylated PEAD and HEP. Methoxy polyethylene glycol (mPEG)‐b‐cationic PEAD diblock copolymers are synthesized and complexed with HEP to create a stable “coacersome” structure. Water‐soluble mPEG moiety assembles on the surface of coacersomes in aqueous conditions and creates a steric barrier to avoid aggregation of coacersomes. The coacersomes are able to maintain their initial spherical morphology and size for longer durations in the presence of competing ions, such as 0.3 m NaCl. Additionally, the coacersomes exhibit biocompatibility toward human dermal fibroblasts, a high loading efficiency (>96%) for encapsulation of bone morphogenetic protein 2 (BMP‐2), and a sustained release profile up to 28 days. The BMP‐2‐loaded coacersomes further exhibit increased osteogenic differentiation of human mesenchymal stem cells (hMSCs). The developed coacersome structures have the potential to be utilized as effective carriers for therapeutic protein delivery.
A methoxy polyethylene glycol‐b‐cationic poly(ethylene arginylamino aspartate diglyceride) (mPEG‐b‐cationic PEAD) diblock copolymer forms stable coacersome structure by complexation with heparin and used as bone morphogenetic protein 2 carrier for an efficient in vitro osteogenic differentiation of human mesenchymal stem cells.
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Recent literatures for the conducting materials applied in various tissue engineering such as neural, cardiac and bone tissue engineering and for biosensor applications have been ...reviewed.
Conductive biomaterials with a suitable biocompatibility have been utilized to fabricate in vitro platforms for differentiation of progenitor cell population as well as implantable tissue engineering scaffolds. This review evaluates biocompatibility of various conductive biomaterials and relevant fabrication techniques including coating, incorporation into composites, and functionalization with biological moieties. In addition, recent developments in tissue engineering applications using various conductive biomaterials are discussed in detail. Therefore, this overview could provide fundamental knowledge for engineering strategies in regulation of stem cell differentiation, maintenance of phenotypic characteristics, and design of functional implantable scaffolds for better regenerative medicines.
This review focuses on the recent strategy in the preparation of thiolated polymers and fabrication of their hydrogel matrices. The mechanism involved in the synthesis of thiolated polymers and ...fabrication of thiolated polymer hydrogels is exemplified with suitable schematic representations reported in the recent literature. The 2-iminothiolane namely "Traut's reagent" has been widely used for effectively thiolating the natural polymers such as collagen and gelatin, which contain free amino group in their backbone. The free carboxylic acid group containing polymers such as hyaluronic acid and heparin have been thiolated by using the bifunctional molecules such as cysteamine and L-cysteine via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling reaction. The degree of thiolation in the polymer chain has been widely determined by using Ellman's assay method. The thiolated polymer hydrogels are prepared by disulfide bond formation (or) thiol-ene reaction (or) Michael-type addition reaction. The thiolated polymers such as thiolated gelatin are reacted with polyethylene glycol diacrylate for obtaining interpenetrating polymer network hydrogel scaffolds. Several in vitro cell culture experiments indicate that the developed thiolated polymer hydrogels exhibited biocompatibility and cellular mimicking properties. The developed hydrogel scaffolds efficiently support proliferation and differentiation of various cell types. In the present review article, the thiol-functionalized protein-based biopolymers, carbohydrate-based polymers, and some synthetic polymers have been covered with recently published research articles. In addition, the usage of new thiolated nanomaterials as a crosslinking agent for the preparation of three-dimensional tissue-engineered hydrogels is highlighted.
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The polycation/polyanion based coacervate platform for therapeutic protein delivery finds difficulty in their colloidal stability under physiological environment. To overcome this ...issue, PEGylation could be a versatile strategy to enhance colloidal stability. Herein, a poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation was synthesized, and a series of methoxy polyethylene glycols (mPEG) including mPEG350, mPEG750 and mPEG2000 were attached with PEAD polycation to obtain mPEG350-PEAD, mPEG750-PEAD and mPEG2000-PEAD respectively. The PEAD and mPEGylated PEADs were complexed with heparin (HEP) to fabricate coacervate (Coa) and coacersome (mP_Coa) particles respectively. The colloidal stability of Coa and mP_Coa coacersomes has been investigated by dynamic light scattering (DLS) and microscopic techniques. The vascular endothelial growth factor 165 (VEGF-165) was encapsulated in the Coa or mP_Coa particles and administered to human umbilical vein endothelial cells (HUVECs) to induce a tubular network formation in vitro. All the polycations are highly biocompatible and exhibit more than 94 % of VEGF-165 loading efficiency. An effect of mPEG chain length on colloidal stability of mP_Coa and in vitro tubular formation ability of HUVECs has been investigated.
A polycation-b-poly propylene glycol diblock copolymer (PAAPS-PPG) was synthesized by one pot ring opening polymerization, and a pH responsive PAAPS-PPG/heparin coacervates have been developed for ...enhanced affinity toward human mesenchymal stem cells.▪
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A new poly (3-arginylamino propylene succinate-b-polypropylene glycol) (PAPS-PPG) diblock copolymer was synthesized by one-pot ring opening polymerization (ROP) technique. 1H NMR spectral technique was used to determine arginine conjugation efficiency and molecular weight of final polycations by using 4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA) as an internal standard. The PAAPS-PPG polycation was electrostatically complexed with heparin (HEP) at an isoelectric point to obtain PAAPS-PPG/HEP coacervate microparticles (Coa MPs). The PAAPS-PPG/HEP Coa MPs exhibit acid induced dissociation at pH 5, but PAAPS/HEP Coa MPs without PPG block do not show acid induced dissociation. The PPG block in PAAPS-PPG/HEP Coa MPs increased 20 folds of cell attachment efficiency on human mesenchymal stem cells (hMSCs). The PAAPS-PPG/HEP Coa MPs could effectively encapsulate siRNA and exhibit more than 95% cell viability up to 200μg/mL. Hence, the pH responsive PAAPS-PPG/HEP Coa MPs platform with enhanced stem cell attachment ability would find potential application in gene delivery.
A series of Citrate-PEG-PLGA branched amphiphilic copolymer nanoparticles have been synthesized for tuberculosis drug delivery.
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Poly(lactic-co-glycolic acid) (PLGA)-poly ethylene ...glycol (PEG) based amphiphilic branched copolymer nanoparticles (NPs) have been developed for controlled release of tuberculosis (TB) drugs which include rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ). The drug loading efficiency and the percentage drug content of polymer NPs increase by increasing the amount of PEG content in polymer NPs. The branched PLGA-PEG based copolymer NPs exhibit initial burst release followed by sustained release of RIF for 840 h, INH for 72 h, and PYZ for 720 h. The branched citrate-PEG-PLGA copolymer NPs can act as potential drug carriers when compared to their linear analogues.
Eight heteroleptic nickel(II) and copper(II) complexes of the type M(L1–4)(nap)2 (1–8), where L1–4 = 2-(1-(4-substitutedphenyl)ethylidene)hydrazinecarbothioamide, nap = naproxen, and M = ...Ni(II) or Cu(II), have been synthesized and characterized. UV–vis and EPR spectral studies showed distorted octahedral geometry around metal(II) ions. The cyclic voltammogram of complexes 1–8 displayed an irreversible one-electron transfer process in the cathodic region (E pc = −0.66 to −1.43 V), and nickel(II) complexes 1–4 displayed an irreversible one-electron oxidation process in the anodic region (E pa = 0.75 to 1.10 V). The obtained magnetic moment values (1.82–1.93 μB) for copper(II) complexes 5–8 indicate distortion from octahedral geometry, which is further supported by EPR studies. The geometry of the complexes is retained in both solid and solution phases as evidenced from UV–vis and EPR studies. All the complexes showed stability for almost 72 h in biologically relevant solutions. The reducing ability of the copper(II) complexes in the presence of ascorbic acid was analyzed by UV–vis and cyclic voltammetry techniques, which indicates the reduction of the copper(II) to a copper(I) center, and possible interaction within the cells. An in vitro antiproliferative study revealed the nontoxic nature of complexes to normal human dermal fibroblast (NHDF) up to a concentration of 100 ng/mL. The antiproliferative activity of the complexes was tested against three cancerous (human breast adenocarcinoma (MCF-7), hepatoma (HepG2), and lung (A549)) cell lines using MTT reduction assay, which showed enhanced activity for complexes 4 and 8 containing the hydrophobic substituent. Apoptotic and cellular uptake studies showed that complex 8 is readily taken up by HepG2 cell lines and induces ROS-mediated mitochondrial and caspase-dependent apoptosis. In silico studies indicated hydrogen bonding, hydrophobic, and π-pair (π–π, π–σ, and π–cation) interactions between the complexes and EGFR/VEGFR2 kinase receptors.
The purpose of the study was to develop caffeine-loaded gold nanoparticles (AuNPs) using a poly(lactic acid)-polyethylene glycol-poly(lactic acid) (PLA-PEG-PLA) polymer to enhance the ...anti-inflammatory activity of caffeine. Caffeine-loaded AuNPs were conjugated to PLA-PEG-PLA copolymer matrix via π-back bond between AuNPs and the ester carbonyl group of the polyester. The π-back bonded ester carbonyl oxygen strongly interacted with the caffeine molecule and exhibited enhanced anti-inflammatory activity. The physico-chemical characteristics of the resulting nanoconjugates were evaluated by a series of microscopic, diffraction, and spectroscopic methods. In vitro assays indicated increasing membrane stabilization of red blood cells and enhanced inhibition of protein denaturation.
The titanium dioxide (TiO2) and zinc oxide (ZnO) nanomaterials are widely used for several biomedical applications because of their semiconductor property. The present study demonstrates a strategy ...for synthesis of zinc oxide nanorod (ZnONR) doped titanium dioxide nanosheets (ZnONR@TiONS) via hydrothermal method. A series of characterization techniques indicated that TiONS exhibited band gap energy of 3.09eV, while the ZnONR@TiONS showed 2.83eV. XPS analysis confirmed the 4+ oxidation state of TiONS and 2+ oxidation state of ZnONR. In vitro cytotoxicity test indicated that the ZnONR@TiONS showed 99% of cell viability without any toxicity under 50μg/mL of concentrations.
