The treatment of critical-sized bone defects caused by tumor removal, skeletal injuries, or infec... more The treatment of critical-sized bone defects caused by tumor removal, skeletal injuries, or infections continues to pose a major clinical challenge. A popular potential alternative solution to autologous bone grafts is a tissue-engineered approach that utilizes the combination of mesenchymal stromal/stem cells (MSCs) with synthetic biomaterial scaffolds. This approach aims to support new bone formation by mimicking many of the biochemical and biophysical cues present within native bone. Regrettably, osteocyte cells, crucial for bone maturation and homeostasis, are rarely produced within MSC-seeded scaffolds, thereby restricting the development of fully mature cortical bone from these synthetic implants. In this work, we have constructed a multimodal scaffold by combining electrospun poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds with poly(ethylene glycol) (PEG)-based hydrogels that mimic the functional unit of cortical bone, osteon (osteonmimetic) scaffolds. These scaffolds were decorated with a novel bone morphogenic protein-6 (BMP6) peptide (BMP6p) after our findings revealed that the BMP6p drives higher levels of Smad signaling than the full-length protein counterpart, soluble or when bound to the PEG hydrogel backbone. We show that our osteon-mimetic scaffolds, in presenting concentric layers of BMP6p-PEG hydrogel overlaid on MSCseeded PLGA nanofibers, promoted the rapid formation of osteocyte-like cells with a phenotypic dendritic morphology, producing early osteocyte markers, including E11/gp38 (E11). Maturation of these osteocyte-like cells was further confirmed by the observation of significant dentin matrix protein 1 (DMP1) throughout our bilayered scaffolds after 3 weeks, even when cultured in a medium without dexamethasone (DEX) or any other osteogenic supplements. These results demonstrate that these osteon-mimetic scaffolds, in presenting biochemical and topographical cues reminiscent of the forming osteon, can drive the formation of osteocytelike cells in vitro from hBMSCs without the need for any osteogenic factor media supplementation.
Journal of Regenerative Biology and Medicine, 2022
The advancement of science and medicine in recent decades has improved human health care resultin... more The advancement of science and medicine in recent decades has improved human health care resulting in increased quality and length of life. The progress of regenerative medicine has opened new venues for therapeutic techniques to treat cancer and traumatic injuries. The development of three-dimensional materials that can closely mimic the conditions cells are presented with in vivo is a great challenge in biomaterials development for regenerative medicine applications. Synthesised scaffolds should be tuneable in terms of their mechanical properties to be suited for regenerative applications. In addition, these materials should provide cells with a platform such that they can survive, differentiate, and proliferate. The incorporation of ECM proteins binding peptides into the polymeric network can be an effective strategy to provide cellsupporting biomaterials with the additional benefit of supporting cells to generate their in vivo-like microenvironment within hydrogels.
Vaginal drug delivery is regarded as a promising route against women-related health issues such a... more Vaginal drug delivery is regarded as a promising route against women-related health issues such as unwanted pregnancies and sexually transmitted infections. However, only a very few studies have been reported on the use of hydrogel rings with low cytotoxicity for vaginal drug delivery applications. Moreover, the effect of nanoparticles on hydrogel vaginal rings has not been clearly evaluated. To overcome these challenges, we hereby developed nanocomposite hydrogel rings based on polyacrylamide-sodium carboxymethyl cellulose-montmorillonite nanoparticles in the ring-shaped aluminum mold for controlled drug delivery. The hydrogel rings were synthesized by using N,N′-methylene bisacrylamide, N,N,N′,N′-tetramethyl ethylene diamine, and ammonium persulfate, as a crosslinker, accelerator, and initiator, respectively. The obtained rings were 5.5 cm in diameters and 0.5 cm in rims. Chemical structures of the nanocomposite rings were confirmed by Fourier transform infrared, and Nuclear Magnetic Resonance spectroscopies. Additionally, the swelling ratio of hydrogels was appeared to be adjusted by the introduction of nanoparticles. In vitro release experiment of methylene blue, as a hydrophilic model drug, revealed that the nanocomposite rings could not only reduce burst effect (almost more than twice), but also achieve prolonged release for 15 days in the vaginal fluid simulant which mimic the vaginal conditions at pH of almost 4.2, and a temperature of 37°C. Importantly, the resultant hydrogel rings with or without various concentrations of montmorillonite showed low cytotoxicity toward human skin fibroblasts. Furthermore, different antibacterial activities against Escherichia coli were observed for various concentrations of montmorillonite in hydrogels. These results suggest the great potential of montmorillonite-based hydrogel rings for vaginal drug delivery.
Capturing cell-secreted extracellular matrix (ECM) proteins through cooperative binding with high... more Capturing cell-secreted extracellular matrix (ECM) proteins through cooperative binding with high specificity and affinity is an important function of native tissue matrices during both tissue homeostasis and repair. However, while synthetic hydrogels, such as those based on poly(ethylene glycol) (PEG), are often proposed as ideal materials to deliver human mesenchymal stem cells (hMSCs) to sites of injury to enable tissue repair, they do not have this capabilitya capability that would enable cells to actively remodel their local extracellular microenvironment and potentially provide the required feedback control for more effective tissue genesis. In this work, we detail a methodology that engenders poly-(ethylene glycol) (PEG)-based two-dimensional substrates and three-dimensional porous hydrogels with the ability to capture desired extracellular matrix (ECM) proteins with high specificity. This " encoded " ECM protein capture is achieved by decorating the PEG-based materials with protein binding peptides (PBPs) synthesized to be specific in their binding of fibronectin, laminin, and collagen I, which are not only the most omnipresent ECM proteins in human tissues but, as we confirmed, are also secreted to differing extents by hMSCs under in vitro maintenance conditions. By encapsulating hMSCs into these PBP-functionalized hydrogels, and culturing them in protein-free maintenance media, we demonstrate that these PBPs not only actively recruit targeted ECM proteins as they are secreted from hMSCs but also retain them to much higher levels compared to nonfunctionalized gels. This novel approach thus enables the fabrication of encoded surfaces and hydrogels that capture cell-secreted proteins, with high specificity and affinity, in a programmable manner, ready for applications in many bioengineering applications, including bioactive surface coatings, bioassays, stem cell culture, tissue engineering, and regenerative medicine.
The potential for the clinical application of stem cells in tissue regeneration is clearly signif... more The potential for the clinical application of stem cells in tissue regeneration is clearly significant. However, this potential has remained largely unrealized owing to the persistent challenges in reproducibly, with tight quality criteria, and expanding and controlling the fate of stem cells in vitro and in vivo. Tissue engineering approaches that rely on reformatting traditional Food and Drug Administration-approved biomedical polymers from fixation devices to porous scaffolds have been shown to lack the complexity required for in vitro stem cell culture models or translation to in vivo applications with high efficacy. This realization has spurred the development of advanced mimetic biomaterials and scaffolds to increasingly enhance our ability to control the cellular microenvironment and, consequently, stem cell fate. New insights into the biology of stem cells are expected to eventuate from these advances in material science, in particular, from synthetic hydrogels that display ...
The potential for the clinical application of stem cells in tissue regeneration is clearly signif... more The potential for the clinical application of stem cells in tissue regeneration is clearly significant. However, this potential has remained largely unrealized owing to the persistent challenges in reproducibly, with tight quality criteria, and expanding and controlling the fate of stem cells in vitro and in vivo. Tissue engineering approaches that rely on reformatting traditional Food and Drug Administration-approved biomedical polymers from fixation devices to porous scaffolds have been shown to lack the complexity required for in vitro stem cell culture models or translation to in vivo applications with high efficacy. This realization has spurred the development of advanced mimetic biomaterials and scaffolds to increasingly enhance our ability to control the cellular microenvironment and, consequently, stem cell fate. New insights into the biology of stem cells are expected to eventuate from these advances in material science, in particular, from synthetic hydrogels that display physicochemical properties reminiscent of the natural cell microenvironment and that can be engineered to display or encode essential biological cues. Merging these advanced biomaterials with high-throughput methods to systematically, and in an unbiased manner, probe the role of scaffold biophysical and biochemical elements on stem cell fate will permit the identification of novel key stem cell behavioral effectors, allow improved in vitro replication of requisite in vivo niche functions, and, ultimately, have a profound impact on our understanding of stem cell biology and unlock their clinical potential in tissue engineering and regenerative medicine.
In this article, silver and magnetite nanofillers were synthesized in modified κ-carrageenan hydr... more In this article, silver and magnetite nanofillers were synthesized in modified κ-carrageenan hydrogels using the in situ method. The effect of metallic nanoparticles in gastro-intestinal tract (GIT) release of a model drug (methylene blue) has been investigated. The effect of nanoparticles loading and genipin cross-linking on GIT release of nanocomposite is also studied to finally provide the most suitable drug carrier system.
Kappa-carrageenan/ polyvinyl alcohol cross-linked hydrogels was formulated using genipin as a nat... more Kappa-carrageenan/ polyvinyl alcohol cross-linked hydrogels was formulated using genipin as a natural and non-toxic cross-linker to achieve a controlled drug release. β-carotene was immobilized and the release study was evaluated under in vitro conditions. Monitoring β-carotene release was carried out by structure modification using cross-linker and minimization of burst release. It was found that using genipin can stop burst release in the hydrogels and control active material better than native films as a result of structural modification. This suggests that the burst release is depended highly on the degree of cross-linking and the mesh space available for drug diffusion. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are carried out to study the characteristics changes of native and cross-linked hydrogels. Also, field emission scanning electron microscope (FESEM) was performed to study microstructure of hydgels. The transport mechanism seems to be determined by the strength of the gel network due to genipin concentration changes. Finally, diffusion coefficient is determined for native and cross-linked hydrogel.
In this article, silver and magnetite nanofillers were synthesized in modified -carrageenan hydr... more In this article, silver and magnetite nanofillers were synthesized in modified -carrageenan hydrogels using the in situ method. The effect of metallic nanoparticles in gastro-intestinal tract (GIT) release of a model drug (methylene blue) has been investigated. The effect of nanoparticles loading and genipin cross-linking on GIT release of nanocomposite is also studied to finally provide the most suitable drug carrier system. In vitro release studies revealed that using metallic nanocomposites hydrogels in GIT studies can improve the drug release in intestine and minimize it in the stomach. It was found that crosslinking and nanofiller loading can significantly improve the targeted release. Therefore, applying metallic nanoparticles seems to be a promising strategy to develop GIT controlled drug delivery.
"In this article, modified -carrageenan hydrogel nanocomposites were synthesized to increase the... more "In this article, modified -carrageenan hydrogel nanocomposites were synthesized to increase the release ability of carrageenan hydrogels under gastrointestinal conditions. The effect of MgO nanoparticle loading in a model drug (methylene blue) release is investigated. Characterization of hydrogels were carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FESEM) and Differential Scanning Calorimetry (DSC). Genipin was used to increase
the delivery performance in gastrointestinal tract delivery by decreasing release in simulated stomach conditions and increasing release in simulated intestine conditions. It is shown that the amount of methylene blue released from genipin-cross-linked nanocomposites can be 67.5% higher in intestine medium and 56% lower in the stomach compared to -carrageenan hydrogel. It was found that by changing the nanoparticle loading and genipin concentration in the composite, the amount of drug released can be monitored. Therefore, applying nanoparticles appears to be a potential strategy to develop controlled drug delivery especially in gastrointestinal tract studies."
"We studied a model system of controlled drug release using beta-carotene and κ-carrageenan/NaCMC... more "We studied a model system of controlled drug release using beta-carotene and κ-carrageenan/NaCMC hydrogel as a drug and a device, respectively. Different concentrations of genipin were added to crosslink the beta-carotene loaded beads by using the dripping method. Results have shown that the cross-linked beads possess lower swelling ability in all pH conditions (pH 1.2 and 7.4), and swelling ratio decreases with increasing genipin concentration. Microstructure study shows that cross-linking has enhanced the stability and structure of the beads network. Determination of diffusion coefficient for the release of encapsulated beta-carotene indicates less diffusivity when beads are cross-linked. Swelling models using adaptive neuro fuzzy show that using genipin as a cross-linker in the kC/NaCMC hydrogels affects the transport mechanism. The model shows very good agreement with the experimental data that indicates that applying ANFIS modelling is an accurate, rapid and simple way to model in such a case for controlled release applications.
In this article, genipin cross-linked kappa-cararageenan/ hydroxyethyl cellulose hydrogels are pr... more In this article, genipin cross-linked kappa-cararageenan/ hydroxyethyl cellulose hydrogels are prepared and the effect of cross-linking on hydrogels characteristics is investigated. Swelling and transform mechanism of both native and cross-linked gels in different pH is also studied. It is found that the concentration of genipin can affect the physical stability of gels. An optimum concentration of cross-linker that hydrogel molecular structure can be in its most stable form is also discussed. Native hydrogels exhibited more swelling in alkaline medium than acidic and neutral; however, by increasing the cross-linker concentration, the swelling ability in neutral medium increased so that genipin cross-linker hydrogels could swell in pH 7 more that pH 1.2 and 12. Fourier transform infrared spectroscopy (FTIR) is applied to study the formation of new bonding due to genipin reactions and explain hydrogels stability in various concentrations. Differential scanning calorimetry (DSC) measurements reveal that by increasing genipin, gels ability to hold water increases to some point and then decreases due to less structural stability. X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM) test were performed to study the crystallinity changes and microstructure of hydrogels. Finally, power law model is applied to study the transform mechanism of hydrogels.
In this article, the physical stability of carrageenan hydrogels was improved for in vitro contro... more In this article, the physical stability of carrageenan hydrogels was improved for in vitro controlled drug delivery in different pH mediums. Physical property changes were studied using various characterization tests. The effect of modification on swelling behavior of hydrogels as well as swelling kinetics of hydrogels was also investigated. It was found that the addition of genipin to the hydrogels can increase the physical properties of carrageenan hydrogels. An optimum genipin concentration in which molecular structure of hydrogel can be in its most stable form is also determined. The study of swelling kinetics revealed that the modification has resulted in the relaxation of carageenan molecules and the swelling mechanism from a diffusion-controlled mechanism is changed to a polymer relaxation controlled mechanism. Release study shows that by changing the genipin concentration in the hydrogel drug release can be controlled.
Journal of The Taiwan Institute of Chemical Engineers
In this article, synthesis and rheological behavior of Fe2O3 magnetic nanoparticles ferrofluids i... more In this article, synthesis and rheological behavior of Fe2O3 magnetic nanoparticles ferrofluids in paraffin base as well as their magnetoviscos effects have been investigated. In order to prepare the ferrofluids, ball mill and ultrasonic bath were used. Then rheological behavior of the system was studied using a standard rotating rheometer. Oleic acid was used to stabilize ferrofluids. Also the effect of magnetic field on the fluid was studied. It is shown that using magnetic field will cause noticeable increase in viscosity at constant shear rate. This increase in viscosity, however, is limited to a specific rate of magnetic field. Also, a novel correlation for predicting temperature dependency of fluid has been presented.► We used Ball mill to prepare ferrofluid. ► We studied volume fraction and shear thinning in the fluid. ► A novel correlation for predicting temperature dependency of fluid is presented. ► We investigated magnetoviscos effects on the fluid.
In this study, a new model of predicting effective thermal conductivity for Al2O3 nanoparticles d... more In this study, a new model of predicting effective thermal conductivity for Al2O3 nanoparticles dispersed in ethylene glycol (EG) and water regarding the shape factor and volume fraction of nanoparticles, is developed. It has been proved that considering Al2O3 particles as spherical molecules is not acceptable assumption. Starting from Brailsford and Major general equation for multi-component materials, an equation has been derived that is based on shape factor of nanoparticle. Also, the according to morphology of Al2O3, a new shape factor for these nanoparticles witch is more realistic, is given which TEM images confirm this. Finally, theoretical results have been compared with experimental data. It is shown that shape factor value applied for Al2O3 / Water system cannot be used for Al2O3/ EG system and EG molecules cover Al2O3 nanoparticles differently that must be considered in equations.
In this study, MgO nanoparticles are applied to
control the initial burst release by modificatio... more In this study, MgO nanoparticles are applied to
control the initial burst release by modification of matrix
structure, thereby affecting the release mechanism. The
effects of MgO nanofiller loading on the in vitro release of
a model drug are investigated. Surface topography and
release kinetics of hydrogel nanocomposites are also
studied in order to have better insight into the release
mechanism. It was found that the incorporation of MgO
nanofillers can significantly decrease the initial burst
release. The effect of genipin (GN) on burst release was
also compared with MgO nanoparticles, and it was found
that the impact of MgO on burst release reduction is more
obvious than GN; however, GN cross-linking caused
greater final release compared to blanks and nanocomposites.
To confirm the capability of nanocomposite
hydrogels to reduce burst release, the release of b-carotene
in Simulated Gastric Fluid and Simulated Intestinal Fluid
was also carried out. Thus, the application of MgO nanoparticles
seems to be a promising strategy to control burst
release.
The treatment of critical-sized bone defects caused by tumor removal, skeletal injuries, or infec... more The treatment of critical-sized bone defects caused by tumor removal, skeletal injuries, or infections continues to pose a major clinical challenge. A popular potential alternative solution to autologous bone grafts is a tissue-engineered approach that utilizes the combination of mesenchymal stromal/stem cells (MSCs) with synthetic biomaterial scaffolds. This approach aims to support new bone formation by mimicking many of the biochemical and biophysical cues present within native bone. Regrettably, osteocyte cells, crucial for bone maturation and homeostasis, are rarely produced within MSC-seeded scaffolds, thereby restricting the development of fully mature cortical bone from these synthetic implants. In this work, we have constructed a multimodal scaffold by combining electrospun poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds with poly(ethylene glycol) (PEG)-based hydrogels that mimic the functional unit of cortical bone, osteon (osteonmimetic) scaffolds. These scaffolds were decorated with a novel bone morphogenic protein-6 (BMP6) peptide (BMP6p) after our findings revealed that the BMP6p drives higher levels of Smad signaling than the full-length protein counterpart, soluble or when bound to the PEG hydrogel backbone. We show that our osteon-mimetic scaffolds, in presenting concentric layers of BMP6p-PEG hydrogel overlaid on MSCseeded PLGA nanofibers, promoted the rapid formation of osteocyte-like cells with a phenotypic dendritic morphology, producing early osteocyte markers, including E11/gp38 (E11). Maturation of these osteocyte-like cells was further confirmed by the observation of significant dentin matrix protein 1 (DMP1) throughout our bilayered scaffolds after 3 weeks, even when cultured in a medium without dexamethasone (DEX) or any other osteogenic supplements. These results demonstrate that these osteon-mimetic scaffolds, in presenting biochemical and topographical cues reminiscent of the forming osteon, can drive the formation of osteocytelike cells in vitro from hBMSCs without the need for any osteogenic factor media supplementation.
Journal of Regenerative Biology and Medicine, 2022
The advancement of science and medicine in recent decades has improved human health care resultin... more The advancement of science and medicine in recent decades has improved human health care resulting in increased quality and length of life. The progress of regenerative medicine has opened new venues for therapeutic techniques to treat cancer and traumatic injuries. The development of three-dimensional materials that can closely mimic the conditions cells are presented with in vivo is a great challenge in biomaterials development for regenerative medicine applications. Synthesised scaffolds should be tuneable in terms of their mechanical properties to be suited for regenerative applications. In addition, these materials should provide cells with a platform such that they can survive, differentiate, and proliferate. The incorporation of ECM proteins binding peptides into the polymeric network can be an effective strategy to provide cellsupporting biomaterials with the additional benefit of supporting cells to generate their in vivo-like microenvironment within hydrogels.
Vaginal drug delivery is regarded as a promising route against women-related health issues such a... more Vaginal drug delivery is regarded as a promising route against women-related health issues such as unwanted pregnancies and sexually transmitted infections. However, only a very few studies have been reported on the use of hydrogel rings with low cytotoxicity for vaginal drug delivery applications. Moreover, the effect of nanoparticles on hydrogel vaginal rings has not been clearly evaluated. To overcome these challenges, we hereby developed nanocomposite hydrogel rings based on polyacrylamide-sodium carboxymethyl cellulose-montmorillonite nanoparticles in the ring-shaped aluminum mold for controlled drug delivery. The hydrogel rings were synthesized by using N,N′-methylene bisacrylamide, N,N,N′,N′-tetramethyl ethylene diamine, and ammonium persulfate, as a crosslinker, accelerator, and initiator, respectively. The obtained rings were 5.5 cm in diameters and 0.5 cm in rims. Chemical structures of the nanocomposite rings were confirmed by Fourier transform infrared, and Nuclear Magnetic Resonance spectroscopies. Additionally, the swelling ratio of hydrogels was appeared to be adjusted by the introduction of nanoparticles. In vitro release experiment of methylene blue, as a hydrophilic model drug, revealed that the nanocomposite rings could not only reduce burst effect (almost more than twice), but also achieve prolonged release for 15 days in the vaginal fluid simulant which mimic the vaginal conditions at pH of almost 4.2, and a temperature of 37°C. Importantly, the resultant hydrogel rings with or without various concentrations of montmorillonite showed low cytotoxicity toward human skin fibroblasts. Furthermore, different antibacterial activities against Escherichia coli were observed for various concentrations of montmorillonite in hydrogels. These results suggest the great potential of montmorillonite-based hydrogel rings for vaginal drug delivery.
Capturing cell-secreted extracellular matrix (ECM) proteins through cooperative binding with high... more Capturing cell-secreted extracellular matrix (ECM) proteins through cooperative binding with high specificity and affinity is an important function of native tissue matrices during both tissue homeostasis and repair. However, while synthetic hydrogels, such as those based on poly(ethylene glycol) (PEG), are often proposed as ideal materials to deliver human mesenchymal stem cells (hMSCs) to sites of injury to enable tissue repair, they do not have this capabilitya capability that would enable cells to actively remodel their local extracellular microenvironment and potentially provide the required feedback control for more effective tissue genesis. In this work, we detail a methodology that engenders poly-(ethylene glycol) (PEG)-based two-dimensional substrates and three-dimensional porous hydrogels with the ability to capture desired extracellular matrix (ECM) proteins with high specificity. This " encoded " ECM protein capture is achieved by decorating the PEG-based materials with protein binding peptides (PBPs) synthesized to be specific in their binding of fibronectin, laminin, and collagen I, which are not only the most omnipresent ECM proteins in human tissues but, as we confirmed, are also secreted to differing extents by hMSCs under in vitro maintenance conditions. By encapsulating hMSCs into these PBP-functionalized hydrogels, and culturing them in protein-free maintenance media, we demonstrate that these PBPs not only actively recruit targeted ECM proteins as they are secreted from hMSCs but also retain them to much higher levels compared to nonfunctionalized gels. This novel approach thus enables the fabrication of encoded surfaces and hydrogels that capture cell-secreted proteins, with high specificity and affinity, in a programmable manner, ready for applications in many bioengineering applications, including bioactive surface coatings, bioassays, stem cell culture, tissue engineering, and regenerative medicine.
The potential for the clinical application of stem cells in tissue regeneration is clearly signif... more The potential for the clinical application of stem cells in tissue regeneration is clearly significant. However, this potential has remained largely unrealized owing to the persistent challenges in reproducibly, with tight quality criteria, and expanding and controlling the fate of stem cells in vitro and in vivo. Tissue engineering approaches that rely on reformatting traditional Food and Drug Administration-approved biomedical polymers from fixation devices to porous scaffolds have been shown to lack the complexity required for in vitro stem cell culture models or translation to in vivo applications with high efficacy. This realization has spurred the development of advanced mimetic biomaterials and scaffolds to increasingly enhance our ability to control the cellular microenvironment and, consequently, stem cell fate. New insights into the biology of stem cells are expected to eventuate from these advances in material science, in particular, from synthetic hydrogels that display ...
The potential for the clinical application of stem cells in tissue regeneration is clearly signif... more The potential for the clinical application of stem cells in tissue regeneration is clearly significant. However, this potential has remained largely unrealized owing to the persistent challenges in reproducibly, with tight quality criteria, and expanding and controlling the fate of stem cells in vitro and in vivo. Tissue engineering approaches that rely on reformatting traditional Food and Drug Administration-approved biomedical polymers from fixation devices to porous scaffolds have been shown to lack the complexity required for in vitro stem cell culture models or translation to in vivo applications with high efficacy. This realization has spurred the development of advanced mimetic biomaterials and scaffolds to increasingly enhance our ability to control the cellular microenvironment and, consequently, stem cell fate. New insights into the biology of stem cells are expected to eventuate from these advances in material science, in particular, from synthetic hydrogels that display physicochemical properties reminiscent of the natural cell microenvironment and that can be engineered to display or encode essential biological cues. Merging these advanced biomaterials with high-throughput methods to systematically, and in an unbiased manner, probe the role of scaffold biophysical and biochemical elements on stem cell fate will permit the identification of novel key stem cell behavioral effectors, allow improved in vitro replication of requisite in vivo niche functions, and, ultimately, have a profound impact on our understanding of stem cell biology and unlock their clinical potential in tissue engineering and regenerative medicine.
In this article, silver and magnetite nanofillers were synthesized in modified κ-carrageenan hydr... more In this article, silver and magnetite nanofillers were synthesized in modified κ-carrageenan hydrogels using the in situ method. The effect of metallic nanoparticles in gastro-intestinal tract (GIT) release of a model drug (methylene blue) has been investigated. The effect of nanoparticles loading and genipin cross-linking on GIT release of nanocomposite is also studied to finally provide the most suitable drug carrier system.
Kappa-carrageenan/ polyvinyl alcohol cross-linked hydrogels was formulated using genipin as a nat... more Kappa-carrageenan/ polyvinyl alcohol cross-linked hydrogels was formulated using genipin as a natural and non-toxic cross-linker to achieve a controlled drug release. β-carotene was immobilized and the release study was evaluated under in vitro conditions. Monitoring β-carotene release was carried out by structure modification using cross-linker and minimization of burst release. It was found that using genipin can stop burst release in the hydrogels and control active material better than native films as a result of structural modification. This suggests that the burst release is depended highly on the degree of cross-linking and the mesh space available for drug diffusion. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are carried out to study the characteristics changes of native and cross-linked hydrogels. Also, field emission scanning electron microscope (FESEM) was performed to study microstructure of hydgels. The transport mechanism seems to be determined by the strength of the gel network due to genipin concentration changes. Finally, diffusion coefficient is determined for native and cross-linked hydrogel.
In this article, silver and magnetite nanofillers were synthesized in modified -carrageenan hydr... more In this article, silver and magnetite nanofillers were synthesized in modified -carrageenan hydrogels using the in situ method. The effect of metallic nanoparticles in gastro-intestinal tract (GIT) release of a model drug (methylene blue) has been investigated. The effect of nanoparticles loading and genipin cross-linking on GIT release of nanocomposite is also studied to finally provide the most suitable drug carrier system. In vitro release studies revealed that using metallic nanocomposites hydrogels in GIT studies can improve the drug release in intestine and minimize it in the stomach. It was found that crosslinking and nanofiller loading can significantly improve the targeted release. Therefore, applying metallic nanoparticles seems to be a promising strategy to develop GIT controlled drug delivery.
"In this article, modified -carrageenan hydrogel nanocomposites were synthesized to increase the... more "In this article, modified -carrageenan hydrogel nanocomposites were synthesized to increase the release ability of carrageenan hydrogels under gastrointestinal conditions. The effect of MgO nanoparticle loading in a model drug (methylene blue) release is investigated. Characterization of hydrogels were carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FESEM) and Differential Scanning Calorimetry (DSC). Genipin was used to increase
the delivery performance in gastrointestinal tract delivery by decreasing release in simulated stomach conditions and increasing release in simulated intestine conditions. It is shown that the amount of methylene blue released from genipin-cross-linked nanocomposites can be 67.5% higher in intestine medium and 56% lower in the stomach compared to -carrageenan hydrogel. It was found that by changing the nanoparticle loading and genipin concentration in the composite, the amount of drug released can be monitored. Therefore, applying nanoparticles appears to be a potential strategy to develop controlled drug delivery especially in gastrointestinal tract studies."
"We studied a model system of controlled drug release using beta-carotene and κ-carrageenan/NaCMC... more "We studied a model system of controlled drug release using beta-carotene and κ-carrageenan/NaCMC hydrogel as a drug and a device, respectively. Different concentrations of genipin were added to crosslink the beta-carotene loaded beads by using the dripping method. Results have shown that the cross-linked beads possess lower swelling ability in all pH conditions (pH 1.2 and 7.4), and swelling ratio decreases with increasing genipin concentration. Microstructure study shows that cross-linking has enhanced the stability and structure of the beads network. Determination of diffusion coefficient for the release of encapsulated beta-carotene indicates less diffusivity when beads are cross-linked. Swelling models using adaptive neuro fuzzy show that using genipin as a cross-linker in the kC/NaCMC hydrogels affects the transport mechanism. The model shows very good agreement with the experimental data that indicates that applying ANFIS modelling is an accurate, rapid and simple way to model in such a case for controlled release applications.
In this article, genipin cross-linked kappa-cararageenan/ hydroxyethyl cellulose hydrogels are pr... more In this article, genipin cross-linked kappa-cararageenan/ hydroxyethyl cellulose hydrogels are prepared and the effect of cross-linking on hydrogels characteristics is investigated. Swelling and transform mechanism of both native and cross-linked gels in different pH is also studied. It is found that the concentration of genipin can affect the physical stability of gels. An optimum concentration of cross-linker that hydrogel molecular structure can be in its most stable form is also discussed. Native hydrogels exhibited more swelling in alkaline medium than acidic and neutral; however, by increasing the cross-linker concentration, the swelling ability in neutral medium increased so that genipin cross-linker hydrogels could swell in pH 7 more that pH 1.2 and 12. Fourier transform infrared spectroscopy (FTIR) is applied to study the formation of new bonding due to genipin reactions and explain hydrogels stability in various concentrations. Differential scanning calorimetry (DSC) measurements reveal that by increasing genipin, gels ability to hold water increases to some point and then decreases due to less structural stability. X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM) test were performed to study the crystallinity changes and microstructure of hydrogels. Finally, power law model is applied to study the transform mechanism of hydrogels.
In this article, the physical stability of carrageenan hydrogels was improved for in vitro contro... more In this article, the physical stability of carrageenan hydrogels was improved for in vitro controlled drug delivery in different pH mediums. Physical property changes were studied using various characterization tests. The effect of modification on swelling behavior of hydrogels as well as swelling kinetics of hydrogels was also investigated. It was found that the addition of genipin to the hydrogels can increase the physical properties of carrageenan hydrogels. An optimum genipin concentration in which molecular structure of hydrogel can be in its most stable form is also determined. The study of swelling kinetics revealed that the modification has resulted in the relaxation of carageenan molecules and the swelling mechanism from a diffusion-controlled mechanism is changed to a polymer relaxation controlled mechanism. Release study shows that by changing the genipin concentration in the hydrogel drug release can be controlled.
Journal of The Taiwan Institute of Chemical Engineers
In this article, synthesis and rheological behavior of Fe2O3 magnetic nanoparticles ferrofluids i... more In this article, synthesis and rheological behavior of Fe2O3 magnetic nanoparticles ferrofluids in paraffin base as well as their magnetoviscos effects have been investigated. In order to prepare the ferrofluids, ball mill and ultrasonic bath were used. Then rheological behavior of the system was studied using a standard rotating rheometer. Oleic acid was used to stabilize ferrofluids. Also the effect of magnetic field on the fluid was studied. It is shown that using magnetic field will cause noticeable increase in viscosity at constant shear rate. This increase in viscosity, however, is limited to a specific rate of magnetic field. Also, a novel correlation for predicting temperature dependency of fluid has been presented.► We used Ball mill to prepare ferrofluid. ► We studied volume fraction and shear thinning in the fluid. ► A novel correlation for predicting temperature dependency of fluid is presented. ► We investigated magnetoviscos effects on the fluid.
In this study, a new model of predicting effective thermal conductivity for Al2O3 nanoparticles d... more In this study, a new model of predicting effective thermal conductivity for Al2O3 nanoparticles dispersed in ethylene glycol (EG) and water regarding the shape factor and volume fraction of nanoparticles, is developed. It has been proved that considering Al2O3 particles as spherical molecules is not acceptable assumption. Starting from Brailsford and Major general equation for multi-component materials, an equation has been derived that is based on shape factor of nanoparticle. Also, the according to morphology of Al2O3, a new shape factor for these nanoparticles witch is more realistic, is given which TEM images confirm this. Finally, theoretical results have been compared with experimental data. It is shown that shape factor value applied for Al2O3 / Water system cannot be used for Al2O3/ EG system and EG molecules cover Al2O3 nanoparticles differently that must be considered in equations.
In this study, MgO nanoparticles are applied to
control the initial burst release by modificatio... more In this study, MgO nanoparticles are applied to
control the initial burst release by modification of matrix
structure, thereby affecting the release mechanism. The
effects of MgO nanofiller loading on the in vitro release of
a model drug are investigated. Surface topography and
release kinetics of hydrogel nanocomposites are also
studied in order to have better insight into the release
mechanism. It was found that the incorporation of MgO
nanofillers can significantly decrease the initial burst
release. The effect of genipin (GN) on burst release was
also compared with MgO nanoparticles, and it was found
that the impact of MgO on burst release reduction is more
obvious than GN; however, GN cross-linking caused
greater final release compared to blanks and nanocomposites.
To confirm the capability of nanocomposite
hydrogels to reduce burst release, the release of b-carotene
in Simulated Gastric Fluid and Simulated Intestinal Fluid
was also carried out. Thus, the application of MgO nanoparticles
seems to be a promising strategy to control burst
release.
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Papers by Hadi Hezaveh
the delivery performance in gastrointestinal tract delivery by decreasing release in simulated stomach conditions and increasing release in simulated intestine conditions. It is shown that the amount of methylene blue released from genipin-cross-linked nanocomposites can be 67.5% higher in intestine medium and 56% lower in the stomach compared to -carrageenan hydrogel. It was found that by changing the nanoparticle loading and genipin concentration in the composite, the amount of drug released can be monitored. Therefore, applying nanoparticles appears to be a potential strategy to develop controlled drug delivery especially in gastrointestinal tract studies."
Read More: http://informahealthcare.com/doi/abs/10.3109/02652048.2011.651501"
control the initial burst release by modification of matrix
structure, thereby affecting the release mechanism. The
effects of MgO nanofiller loading on the in vitro release of
a model drug are investigated. Surface topography and
release kinetics of hydrogel nanocomposites are also
studied in order to have better insight into the release
mechanism. It was found that the incorporation of MgO
nanofillers can significantly decrease the initial burst
release. The effect of genipin (GN) on burst release was
also compared with MgO nanoparticles, and it was found
that the impact of MgO on burst release reduction is more
obvious than GN; however, GN cross-linking caused
greater final release compared to blanks and nanocomposites.
To confirm the capability of nanocomposite
hydrogels to reduce burst release, the release of b-carotene
in Simulated Gastric Fluid and Simulated Intestinal Fluid
was also carried out. Thus, the application of MgO nanoparticles
seems to be a promising strategy to control burst
release.
the delivery performance in gastrointestinal tract delivery by decreasing release in simulated stomach conditions and increasing release in simulated intestine conditions. It is shown that the amount of methylene blue released from genipin-cross-linked nanocomposites can be 67.5% higher in intestine medium and 56% lower in the stomach compared to -carrageenan hydrogel. It was found that by changing the nanoparticle loading and genipin concentration in the composite, the amount of drug released can be monitored. Therefore, applying nanoparticles appears to be a potential strategy to develop controlled drug delivery especially in gastrointestinal tract studies."
Read More: http://informahealthcare.com/doi/abs/10.3109/02652048.2011.651501"
control the initial burst release by modification of matrix
structure, thereby affecting the release mechanism. The
effects of MgO nanofiller loading on the in vitro release of
a model drug are investigated. Surface topography and
release kinetics of hydrogel nanocomposites are also
studied in order to have better insight into the release
mechanism. It was found that the incorporation of MgO
nanofillers can significantly decrease the initial burst
release. The effect of genipin (GN) on burst release was
also compared with MgO nanoparticles, and it was found
that the impact of MgO on burst release reduction is more
obvious than GN; however, GN cross-linking caused
greater final release compared to blanks and nanocomposites.
To confirm the capability of nanocomposite
hydrogels to reduce burst release, the release of b-carotene
in Simulated Gastric Fluid and Simulated Intestinal Fluid
was also carried out. Thus, the application of MgO nanoparticles
seems to be a promising strategy to control burst
release.