β-Tricalcium phosphate (β-TCP) has attracted much attention as an artificial bone substitute owing to its biocompatibility and osteoconductivity. In this study, osteoconductivity of β-TCP bone substitute was enhanced without using growth factors or cells. Dicalcium phosphate dihydrate (DCPD), which is known to possess the highest solubility among calcium phosphates, was coated on β-TCP granules by exposing their surface with acidic calcium phosphate solution. The amount of coated DCPD was regulated by changing the reaction time between β-TCP granules and acidic calcium phosphate solution. Histomorphometry analysis obtained from histological results revealed that the approximately 10mol% DCPD-coated β-TCP granules showed the largest new bone formation compared to DCPD-free β-TCP granules, approximately 2.5mol% DCPD-coated β-TCP granules, or approximately 27mol% DCPD-coated β-TCP granules after 2 and 4weeks of implantation. Based on this finding, we demonstrate that the osteoconductivity of β-TCP granules could be improved by coating their surface with an appropriate amount of DCPD.
Hydrothermally synthesized TiO2nanotubes (TNTs) were first used as a filler for chitosan scaffold for reinforcement purpose. Chitosan-TNTs (CTNTs) scaffolds prepared via direct blending and freeze drying retained cylindrical structure and showed enhanced compressive modulus and reduced degradation rate compared to chitosan membrane which experienced severe shrinkage after rehydration with ethanol. Macroporous interconnectivity with pore size of 70-230μm and porosity of 88% were found in CTNTs scaffolds. Subsequently, the functionalization of CTNTs scaffolds with CaCl2solutions (0.5mM-40.5mM) was conducted at physiological pH. The adsorption isotherm of Ca2+ions onto CTNTs scaffolds fitted well with Freundlich isotherm. CTNTs scaffolds with Ca2+ions showed high biocompatibility by promoting adhesion, proliferation and early differentiation of MG63 in a non-dose dependent manner. CTNTs scaffolds with Ca2+ions can be an alternative for bone regeneration.
Novel alginate-arabic gum (AG) gel membrane coated alginate-ghatti gum (GG) modified montmorillonite (MMT) composite matrices were developed for intragastric flurbiprofen (FLU) delivery by combining floating and mucoadhesion mechanisms. The clay-biopolymer composite matrices containing FLU as core were accomplished by ionic-gelation technique. Effects of polymer-blend (alginate:GG) ratios and crosslinker (CaCl2) concentrations on drug entrapment efficiency (DEE, %) and cumulative drug release after 8h (Q8h, %) were studied to optimize the core matrices by a 32factorial design. The optimized matrices (F-O) demonstrated DEE of 91.69±1.43% and Q8hof 74.96±1.56% with minimum errors in prediction. The alginate-AG gel membrane enveloped optimized matrices (F-O, coated) exhibited superior buoyancy, better ex vivo mucoadhesion and slower drug release rate. The drug release profile of FLU-loaded uncoated and coated optimized matrices was best fitted in Korsmeyer-Peppas model with anomalous diffusion and case-II transport driven mechanism, respectively. The uncoated and coated matrices containing FLU were also characterized for drug-excipients compatibility, drug crystallinity, thermal behaviour and surface morphology. Thus, the newly developed alginate-AG gel membrane coated alginate-GG modified MMT composite matrices are appropriate for intragastric delivery of FLU over an extended period of time with improved therapeutic benefits.
Tissue engineering (TE) is an advanced principle to develop a neotissue that can resemble the original tissue characteristics with the capacity to grow, to repair and to remodel in vivo. This research proposed the optimization and development of nanofiber based scaffold using the new mixture of maghemite (γ-Fe2O3) filled poly-l-lactic acid (PLLA)/thermoplastic polyurethane (TPU) for tissue engineering heart valve (TEHV). The chemical, structural, biological and mechanical properties of nanofiber based scaffold were characterized in terms of morphology, porosity, biocompatibility and mechanical behaviour. Two-level Taguchi experimental design (L8) was performed to optimize the electrospun mats in terms of elastic modulus using uniaxial tensile test where the studied parameters were flow rate, voltage, percentage of maghemite nanoparticles in the content, solution concentration and collector rotating speed. Each run was extended with an outer array to consider the noise factors. The signal-to-noise ratio analysis indicated the contribution percent as follow; Solution concentration>voltage>maghemite %>rotating speed>flow rate. The optimum elastic modulus founded to be 28.13±0.37MPa in such a way that the tensile strain was 31.72% which provided desirability for TEHV. An empirical model was extracted and verified using confirmation test. Furthermore, an ultrafine quality of electrospun nanofibers with 80.32% porosity was fabricated. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and cell attachment using human aortic smooth muscle cells exhibited desirable migration and proliferation over the electrospun mats. The interaction between blood content and the electrospun mats indicated a mutual adaption in terms of clotting time and hemolysis percent. Overall, the fabricated scaffold has the potential to provide the required properties of aortic heart valve.
In this work, binary Zn-0.5Al and ternary Zn-0.5Al-xMg alloys with various Mg contents were investigated as biodegradable materials for implant applications. Compared with Zn-0.5Al (single phase), Zn-0.5Al-xMg alloys consisted of the α-Zn and Mg2(Zn, Al)11 with a fine lamellar structure. The results also revealed that ternary Zn-Al-Mg alloys presented higher micro-hardness value, tensile strength and corrosion resistance compared to the binary Zn-Al alloy. In addition, the tensile strength and corrosion resistance increased with increasing the Mg content in ternary alloys. The immersion tests also indicated that the corrosion rates in the following order Zn-0.5Al-0.5Mg
In this study, nanohybrid materials consisting of graphene oxide (GO), β‑cyclodextrin (CD) and poly(amido amine) dendrimer (DEN) were successfully prepared by covalent bonding. GO-CD and GO-CD-DEN were found to be potential nanocarriers for anticancer drugs including chemotherapeutics (doxorubicin (DOX), camptothecin (CPT)) and photosensitizer (protoporphyrin IX (PpIX)). GO-CD possessed 1.2 times higher DOX-loading capacity than GO due to inclusion of additional DOX to the CD. The drug loading on GO-CD-DEN increased in the order: DOX
A novel approach in the design of a safe, high performance hemodialysis membrane is of great demand. Despite many advantages, the employment of prodigious nanomaterials in hemodialysis membrane is often restricted by their potential threat to health. Hence, this work focusses on designing a biocompatible polyethersulfone (PES) hemodialysis membrane embedded with poly (citric acid)-grafted-multi walled carbon nanotubes (PCA-g-MWCNTs). Two important elements which could assure the safety of the nanocomposite membrane, i.e. (i) dispersion stability and (ii) leaching of MWCNTs were observed. The results showed the improved dispersion stability of MWCNTs in water and organic solvent due to the enriched ratio of oxygen-rich groups which subsequently enhanced membrane separation features. It was revealed that only 0.17% of MWCNTs was leached out during the membrane fabrication process (phase inversion) while no leaching was detected during permeation. In terms of biocompatibility, PES/PCA-g-MWCNT nanocomposite membrane exhibited lesser C3 and C5 activation (189.13 and 5.29ng/mL) and proteins adsorption (bovine serum albumin=4.5μg/cm2, fibrinogen=15.95μg/cm2) as compared to the neat PES membrane, while keeping a normal blood coagulation time. Hence, the PES/PCA-g-MWCNT nanocomposite membrane is proven to have the prospect of becoming a safe and high performance hemodialysis membrane.
Curcumin derivatives have been well-documented due to their natural antioxidant, antimicrobial and anti-inflammatory activities. Curcuminoids have also gained widespread recognition due to their wide range of other activities which include anti-infective, anti-mutagenic, anticancer, anti-coagulant, antiarthrititc, and wound healing potential. Despite of having a wide range of activities, the inherent physicochemical characteristics (poor water solubility, low bioavailability, chemical instability, photodegradation, rapid metabolism and short half-life) of curcumin derivatives limit their pharmaceutical significance. Aiming to overcome these pharmaceutical issues and improving therapeutic efficacy of curcuminoids, newer strategies have been attempted in recent years. These advanced techniques include polymeric nanoparticles, nanocomposite hydrogels, nanovesicles, nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, polymeric micelles and polymeric blend films. Incorporation of curcumin in these delivery systems has shown improved solubility, transmembrane permeability, long-term stability, improved bioavailability, longer plasma half-life, target-specific delivery, and upgraded therapeutic efficacy. In this review, a range of in vitro and in vivo studies have been critically discussed to explore the pharmaceutical significance and therapeutic viability of the advanced delivery systems to improve antioxidant, anti-inflammatory and antimicrobial efficacies of curcumin and its derivatives.
Corrosion prevention in biomaterials has become crucial particularly to overcome inflammation and allergic reactions caused by the biomaterials' implants towards the human body. When these metal implants contacted with fluidic environments such as bloodstream and tissue of the body, most of them became mutually highly antagonistic and subsequently promotes corrosion. Biocompatible implants are typically made up of metallic, ceramic, composite and polymers. The present paper specifically focuses on biocompatible metals which favorably used as implants such as 316L stainless steel, cobalt-chromium-molybdenum, pure titanium and titanium-based alloys. This article also takes a close look at the effect of corrosion towards the implant and human body and the mechanism to improve it. Due to this corrosion delinquent, several surface modification techniques have been used to improve the corrosion behavior of biocompatible metals such as deposition of the coating, development of passivation oxide layer and ion beam surface modification. Apart from that, surface texturing methods such as plasma spraying, chemical etching, blasting, electropolishing, and laser treatment which used to improve corrosion behavior are also discussed in detail. Introduction of surface modifications to biocompatible metals is considered as a "best solution" so far to enhanced corrosion resistance performance; besides achieving superior biocompatibility and promoting osseointegration of biocompatible metals and alloys.
Haptic sensors are essential devices that facilitate human-like sensing systems such as implantable medical devices and humanoid robots. The availability of conducting thin films with haptic properties could lead to the development of tactile sensing systems that stretch reversibly, sense pressure (not just touch), and integrate with collapsible. In this study, a nanocomposite based hemispherical artificial fingertip fabricated to enhance the tactile sensing systems of humanoid robots. To validate the hypothesis, proposed method was used in the robot-like finger system to classify the ripe and unripe tomato by recording the metabolic growth of the tomato as a function of resistivity change during a controlled indention force. Prior to fabrication, a finite element modeling (FEM) was investigated for tomato to obtain the stress distribution and failure point of tomato by applying different external loads. Then, the extracted computational analysis information was utilized to design and fabricate nanocomposite based artificial fingertip to examine the maturity analysis of tomato. The obtained results demonstrate that the fabricated conformable and scalable artificial fingertip shows different electrical property for ripe and unripe tomato. The artificial fingertip is compatible with the development of brain-like systems for artificial skin by obtaining periodic response during an applied load.
ZnO with two different morphologies were used to study the inhibition of Streptococcus sobrinus and Streptococcus mutans which are closely associated with tooth cavity. Rod-like shaped ZnO-A and plate-like shaped ZnO-B were produced using a zinc boiling furnace. The nanopowders were characterized using energy filtered transmission electron microscopy (EFTEM), X-ray diffraction (XRD), photoluminescence (PL) spectroscopy, Raman spectroscopy and dynamic light scattering (DLS) to confirm the properties of the ZnO polycrystalline wurtzite structures. XRD results show that the calculated crystallite sizes of ZnO-A and ZnO-B were 36.6 and 39.4nm, respectively, whereas DLS revealed particle size distributions of 21.82nm (ZnO-A) and 52.21nm (ZnO-B). PL spectra showed ion vacancy defects related to green and red luminescence for both ZnO particles. These defects evolved during the generation of reactive oxygen species which contributed to the antibacterial activity. Antibacterial activity was investigated using microdilution technique towards S. sobrinus and S. mutans at different nanopowder concentrations. Results showed that ZnO-A exhibited higher inhibition on both bacteria compared with ZnO-B. Moreover, S. mutans was more sensitive compared with S. sobrinus because of its higher inhibition rate.
Biocompatible metals have been revolutionizing the biomedical field, predominantly in human implant applications, where these metals widely used as a substitute to or as function restoration of degenerated tissues or organs. Powder metallurgy techniques, in specific the metal injection moulding (MIM) process, have been employed for the fabrication of controlled porous structures used for dental and orthopaedic surgical implants. The porous metal implant allows bony tissue ingrowth on the implant surface, thereby enhancing fixation and recovery. This paper elaborates a systematic classification of various biocompatible metals from the aspect of MIM process as used in medical industries. In this study, three biocompatible metals are reviewed-stainless steels, cobalt alloys, and titanium alloys. The applications of MIM technology in biomedicine focusing primarily on the MIM process setting parameters discussed thoroughly. This paper should be of value to investigators who are interested in state of the art of metal powder metallurgy, particularly the MIM technology for biocompatible metal implant design and development.
Our studies focused on improving the biocompatibility properties of two microfluidic prototyping substrates i.e. polyurethane methacrylate (PUMA) and off-stoichiometry thiol-ene (OSTE-80) polymer by Ar and N2plasma treatment. The contact angle (CA) measurement showed that both plasma treatments inserted oxygen and nitrogen moieties increased the surface energy and hydrophilicity of PUMA and OSTE-80 polymer which corresponded to an increase of nitrogen to carbon ratios (N/C), as measured by XPS, to provide a conducive environment for cell attachments and proliferation. Under the SEM observation, the surface topography of PUMA and OSTE-80 polymer showed minimal changes after the plasma treatments. Furthermore, ageing studies showed that plasma-treated PUMA and OSTE-80 polymer had stable hydrophilicity and nitrogen composition during storage in ambient air for 15days. After in vitro cell culture of human umbilical vein endothelial cells (HUVECs) on these surfaces for 24h and 72h, both trypan blue and alamar blue assays indicated that PUMA and OSTE-80 polymer treated with N2plasma had the highest viability and proliferation. The polar nitrogen moieties, specifically amide groups, encouraged the HUVECs adhesion on the plasma-treated PUMA and OSTE-80 surfaces. Interestingly, PUMA polymer treated with Ar and N2plasma showed different HUVECs morphology which was spindle and cobblestone-shaped respectively after 72h of incubation. On the contrary, a monolayer of well-spread HUVECs formed on the Ar and N2plasma-treated OSTE-80 polymers. These variable morphologies observed can be ascribed to the adherence HUVECs on the different elastic moduli of these surfaces whereby further investigation might be needed. Overall, Ar and N2plasma treatment had successfully altered the surface properties of PUMA and OSTE-80 polymer by increasing its surface energy, hydrophilicity and chemical functionalities to create a biocompatible surface for HUVECs adhesion and proliferation.
Green porous and ecofriendly scaffolds have been considered as one of the potent candidates for tissue engineering substitutes. The objective of this study is to investigate the biocompatibility of hydroxyethyl cellulose (HEC)/silver nanoparticles (AgNPs), prepared by the green synthesis method as a potential host material for skin tissue applications. The substrates which contained varied concentrations of AgNO3(0.4%-1.6%) were formed in the presence of HEC, were dissolved in a single step in water. The presence of AgNPs was confirmed visually by the change of color from colorless to dark brown, and was fabricated via freeze-drying technique. The outcomes exhibited significant porosity of >80%, moderate degradation rate, and tremendous value of water absorption up to 1163% in all samples. These scaffolds of HEC/AgNPs were further characterized by SEM, UV-Vis, ATR-FTIR, TGA, and DSC. All scaffolds possessed open interconnected pore size in the range of 50-150μm. The characteristic peaks of Ag in the UV-Vis spectra (417-421nm) revealed the formation of AgNPs in the blend composite. ATR-FTIR curve showed new existing peak, which implies the oxidation of HEC in the cellulose derivatives. The DSC thermogram showed augmentation in Tgwith increased AgNO3concentration. Preliminary studies of cytotoxicity were carried out in vitro by implementation of the hFB cells on the scaffolds. The results substantiated low toxicity of HEC/AgNPs scaffolds, thus exhibiting an ideal characteristic in skin tissue engineering applications.
Oral cavity is a gateway to the entire body and protection of this gateway is a major goal in dentistry. Plaque biofilm is a major cause of majority of dental diseases and although various biomaterials have been applied for their cure, limitations pertaining to the material properties prevent achievement of desired outcomes. Nanoparticle applications have become useful tools for various dental applications in endodontics, periodontics, restorative dentistry, orthodontics and oral cancers. Off these, silver nanoparticles (AgNPs) have been used in medicine and dentistry due to its antimicrobial properties. AgNPs have been incorporated into biomaterials in order to prevent or reduce biofilm formation. Due to greater surface to volume ratio and small particle size, they possess excellent antimicrobial action without affecting the mechanical properties of the material. This unique property of AgNPs makes these materials as fillers of choice in different biomaterials whereby they play a vital role in improving the properties. This review aims to discuss the influence of addition of AgNPs to various biomaterials used in different dental applications.
Localised and targeted potential of nanocarrier for the eminent anticancer agent paclitaxel (PTX) could provide a great platform towards improvement of efficacy with reduction in associated toxicities, whereas incorporation of TPGS could further facilitate delivery in MDR through alteration of its inherent physicochemical properties. Current article therefore puts into perspective on nanocarrier-based recent researches of PTX with special stress towards TPGS-nanoparticle-mediated delivery in the improvement of cancer treatment and then accompanied with the discussion on distinct influence of the fabrication process. Such dynamic fabrications of the nanoparticulate therapy stimulate cellular interaction with frontier area for future research in tumor targeting potential.
The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.
This study conducted on the structure of modified acrylamide-based hydrogel by synthesizing the nano composites. The hydrogels employed in this study were provided through a combination of acrylamide monomers, sodium carboxymethyl cellulose (NaCMC) and magnesium oxide (MgO) nanoparticles by crosslinking polymerization. N,N,N',N'-tetramethylethylenediamine and ammonium persulfate as the initiator was applied in the structure of the polymer. Findings of the study considered the nano composites consisting of MgO have the highest swelling ratio compared to pure Aam hydrogels. Thus, MgO is an appropriate nanoparticle to be used in the nano composites. Response surface methodology (RSM) based on a central composite design (CCD Design) was applied to optimize the preparation variables of a hydrogel consisted of MgO, NaCMC. With the swelling ratio for acrylamide-based hydrogel as the response, the effects of two variables, i.e. MgO and NaCMC were investigated. The effects of pH, temperature, MgO, and NaCMC on the drug release were investigated using the CCD design. The predicted appropriate drug release conditions for the hydrogel at the highest rate of temperature (37.50 °C) and pH: 4.10, is at its highest value, while the lower drug release is at temperature 38 °C and pH 3.50. With the desired value of MgO (0.01 g) and amount of NaCMC (0.1 g).
Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ± 2 °C, 25 ± 2 °C and 45 ± 2 °C).