Ali Ramazani's research while affiliated with University of Zanjan and other places

Plants have been used for medicinal purposes for thousands of years but they are still finding new uses in modern times. For example, Elaeagnus angustifolia (EA) is a medicinal herb with antinociceptive, anti-inflammatory, antibacterial and antioxidant properties and it is widely used in the treatment of rheumatoid arthritis and osteoarthritis. EA extract was loaded onto poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) (PCL-PEG-PCL/EA) nanofibers and their potential applications for bone tissue engineering were studied. The morphology and chemical properties of the fibers were evaluated using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, contact angle measurements and mechanical tests. All the samples had bead-free morphologies with average diameters ranging from 100 to 200 nm. The response of human cells to the PCL-PEG-PCL/EA nanofibers was evaluated using human dental pulp stem cells (hDPSCs). The hDPSCs had better adhesion and proliferation capacity on the EA loaded nanofibers than on the pristine PCL-PEG-PCL nanofibers. An alizarin red S assay and the alkaline phosphatase activity confirmed that the nanofibrous scaffolds induced osteoblastic performance in the hDPSCs. The quantitative real time polymerase chain reaction results confirmed that the EA loaded nanofibrous scaffolds had significantly upregulated gene expression correlating to osteogenic differentiation. These results suggest that PCL-PEG-PCL/EA nanofibers might have potential applications for bone tissue engineering.

The major challenge of tissue regeneration is to develop three dimensional scaffolds with suitable properties which would mimic the natural extracellular matrix to induce the adhesion, proliferation, and differentiation of cells. Several materials have been used for the preparation of the scaffolds for bone regeneration. In this study, novel ethyl cellulose-grafted-poly (ɛ-caprolactone) (EC-g-PCL)/alginate scaffolds with different contents of nano-hydroxyapatite were prepared by combining electrospinning and freeze-drying methods in order to provide nanofibrous/macroporous structures with good mechanical properties. For this aim, EC-g-PCL nanofibers were obtained with electrospinning, embedded layer-by-layer in alginate solutions containing nano-hydroxyapatite particles, and finally, these constructions were freeze-dried. The scaffolds possess highly porous structures with interconnected pore network. The swelling, porosity, and degradation characteristics of the EC-g-PCL/alginate scaffolds were decreased with the increase in nano-hydroxyapatite contents, whereas increases in the in-vitro biomineralization and mechanical strength were observed as the nano-hydroxyapatite content was increased. The cell response to EC-g-PCL/alginate scaffolds with/or without nano-hydroxyapatite was investigated using human dental pulp stem cells (hDPSCs). hDPSCs displayed a high adhesion, proliferation, and differentiation on nano-hydroxyapatite-incorporated EC-g-PCL/alginate scaffolds compared to pristine EC-g-PCL/alginate scaffold. Overall, these results suggested that the EC-g-PCL/alginate-HA scaffolds might have potential applications in bone tissue engineering.

Background The major challenge of tissue engineering is to develop constructions with suitable properties which would mimic the natural extracellular matrix to induce the proliferation and differentiation of cells. Poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) (PCL-PEG-PCL, PCEC), chitosan (CS), nano-silica (n-SiO2) and nano-hydroxyapatite (n-HA) are biomaterials successfully applied for the preparation of 3D structures appropriate for tissue engineering. Methods We evaluated the effect of n-HA and n-SiO2 incorporated PCEC-CS nanofibers on physical properties and osteogenic differentiation of human dental pulp stem cells (hDPSCs). Fourier transform infrared spectroscopy, field emission scanning electron microscope, transmission electron microscope, thermogravimetric analysis, contact angle and mechanical test were applied to evaluate the physicochemical properties of nanofibers. Cell adhesion and proliferation of hDPSCs and their osteoblastic differentiation on nanofibers were assessed using MTT assay, DAPI staining, alizarin red S staining, and QRT-PCR assay. Results All the samples demonstrated bead-less morphologies with an average diameter in the range of 190–260 nm. The mechanical test studies showed that scaffolds incorporated with n-HA had a higher tensile strength than ones incorporated with n-SiO2. While the hydrophilicity of n-SiO2 incorporated PCEC-CS nanofibers was higher than that of samples enriched with n-HA. Cell adhesion and proliferation studies showed that n-HA incorporated nanofibers were slightly superior to n-SiO2 incorporated ones. Alizarin red S staining and QRT-PCR analysis confirmed the osteogenic differentiation of hDPSCs on PCEC-CS nanofibers incorporated with n-HA and n-SiO2. Conclusion Compared to other groups, PCEC-CS nanofibers incorporated with 15 wt% n-HA were able to support more cell adhesion and differentiation, thus are better candidates for bone tissue engineering applications.

Background: Biodegradable thermosensitive hydrogel scaffolds based on novel three-block PCL-PEG-PCL and penta block PNIPAAm-PCL-PEG-PCL-PNIPAAm copolymers blended with gelatin were prepared and examined on functional behavior of chondrocytes. Methods: In this work, we compared two different thermosensitive hydrogel scaffolds (PNIPAAm-PCL-PEG-PCL-PNIPAAm)/Gelatin and (PCL-PEG-PCL)/Gelatin prepared by TIPS (thermally induced phase separation) method. The feature of copolymers was characterized by FT-IR, ¹H NMR. The lower critical solution temperatures (LCSTs) of aqueous solutions of copolymers were measured by cloud point (turbidity) measurements. We also examined water absorption capacity and swelling ratio. Mechanical features of the prepared hydrogels were evaluated by stress-strain measurements. Thereafter, isolated chondrocytes were cultured on each scaffold for a period of 10 days and cell arrangement and morphology studied pre-and post-plating. Cell survival assay was done by using MTT assay. The transcription level of genes Sox-9, Collagen-II, COMP, MMP-13 and oligomeric matrix protein was monitored by real-time PCR assay. The samples were also stained by Toluidine blue method to monitor the synthesis of proteoglycan. Results: Data demonstrated an increased survival rate in cells coated seeded on scaffolds, especially (PNIPAAm-PCL-PEG-PCL-PNIPAAm)/Gelatin as compared to control cells on the plastic surface. (PNIPAAm-PCL-PEG-PCL-PNIPAAm)/Gelatin had potential to increase the expression of genes Sox-6, Collagen-II, COMP and after 10 days in vitro. Conclusion: Thermosensitive PCEC/Gel and (PNIPAAm-PCEC-PNIPAAm)/Gel hydrogel scaffolds that fabricated by TIPS method possesses useful hydrophilic properties for growth and cell embedding and secretion of extracellular matrix. It can serve as an ideal strategy to promote the formation of cartilage tissue.

A novel thermo/pH sensitive amphiphilic copolymer of Fe3O4@PLA-g-P(NIPAAm-co-HEMA-co-MAA-co-TMSPMA) magnetic nanoparticles comprised of hydrophobic and biodegradable PLA block and hydrophilic P(NIPAAm-co-HEMA-co-MAA-co-TMSPMA) segment was designed and synthesized by combination of ring opening and free radical polymerization methods. The structure and physic-chemical characterization of synthesized nanoparticles were studied and revealed by FTIR, 1HNMR, 13CNMR, SEM, EDX, TEM, DLS-Zeta, XRD, TGA and VSM techniques. Two cationic and anionic anti-cancer drugs of doxorubicin (DOX) and methotrexate (MTX) were loaded simultaneously to nanocomposite for combination cancer chemotherapy proposes. Nanoparticles showed spherical core-shell structure with particle size below 100 nm confirmed with SEM, TEM, DLS and XRD techniques. Encapsulation efficiency of DOX and MTX on nanocarrier was 95.04% and 97.29%, respectively. Dual drug release profile revealed tumor niche assisted release behaviour. Cytotoxicity studies revealed the non-toxicity of novel developed nanocomposite here to MCF-7 cell lines. Antitumor property of DOX/MTX-loaded nanocomposite was significantly higher than free drugs confirmed by MTT assay, DAPI staining, cell cycle, and real-time PCR analysis on MCF7 cell lines. The results of this study showed that this engineered nanocomposite could be effectively used in the targeted delivery of DOX and MTX to the cancerous tissues and for further in vivo uses.

Great efforts have been made to develop drug carriers with the aim of providing predictable therapeutic response. Moreover, combination therapies have become promising strategies for clinical cancer treatment with synergistic effects. The present study purposed to develop a new stimuli-responsive paramagnetic nanocarrier for the intracellular co-delivery of doxorubicin (DOX) and methotrexate (MTX) to the MCF7 cell line. A novel thermo/pH-sensitive amphiphilic paramagnetic nanocomposite comprised of hydrophobic and biodegradable PCL segments and a hydrophilic biocompatible P(NIPAAm-co-HEMA-co-MAA-co-TMSPMA) block was designed and synthesized by combining the ring opening and free radical polymerization methods. The structure and physic-chemical characterization of synthesized nanoparticles and intermediates were studied and revealed using FTIR, HNMR, CNMR, SEM, EDX, TGA, and VSM techniques. DOX and MTX on a nanocarrier achieved 95.04% and 97.29% encapsulation efficiency, respectively. The dual drug release profile revealed tumor niche-assisted release behavior (more drug release was observed at a temperature of 41 °C and pH ≤ 5.4). The antitumor ability of the DOX/MTX-loaded nanocomposite was significantly higher than that of free drugs, confirmed by MTT assay, DAPI staining, cell cycle, and real-time PCR analysis on MCF7 cell lines. Furthermore, the cytotoxicity assay of a nanocarrier to the MCF7 cell line revealed its suitability as an anticancer drug nanocarrier. The results indicated that this engineered dual anticancer drug delivery system ensures increased antitumor activity as well as decreased toxicity in comparison with the free drugs.

Current strategies of tissue engineering are focused on the reconstruction and regeneration of damaged or deformed tissues by grafting of cells with scaffolds and biomolecules. Recently, much interest is given to scaffolds which are based on mimic the extracellular matrix that have induced the formation of new tissues. To return functionality of the organ, the presence of a scaffold is essential as a matrix for cell colonization, migration, growth, differentiation and extracellular matrix deposition, until the tissues are totally restored or regenerated. A wide variety of approaches has been developed either in scaffold materials and production procedures or cell sources and cultivation techniques to regenerate the tissues/organs in tissue engineering applications. This study has been conducted to present an overview of the different scaffold fabrication techniques such as solvent casting and particulate leaching, electrospinning, emulsion freeze-drying, thermally induced phase separation, melt molding and rapid prototyping with their properties, limitations, theoretical principles and their prospective in tailoring appropriate micro-nanostructures for tissue regeneration applications. This review also includes discussion on recent works done in the field of tissue engineering.

Multiwalled carbon nanotubes (MWCNTs) were modified by strong oxidizing agents and were functionalized with toluene 2,4-diisocyanate, and they were used for selective separation of Tl-201 from Pb-201 (radioactive lead). The pristine and functionalized MWCNTs were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. The optimal conditions of experiment, such as pH, amount of adsorbent, and contact time were investigated. The adsorption capacity was evaluated using both Langmuir and Freundlich adsorption isotherm models. The results showed that functionalized MWCNTs have a greater potential for adsorption of lead from aqueous solution, nuclear sample, and separation of Tl-201 from Pb-201.