Publications by authors named "Ali Samadikuchaksaraei"

79 Publications

Cross-linked acellular lung for application in tissue engineering: Effects on biocompatibility, mechanical properties and immunological responses.

Mater Sci Eng C Mater Biol Appl 2021 Mar 5;122:111938. Epub 2021 Feb 5.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

The concept of providing tissue engineering scaffolds with natural physical properties and minimal immunogenicity has not been systematically approached for the lungs yet. Here, the rat acellular lung tissue (ALT) was cross-linked to provide either EDC/NHS cross-linked tissue (EDC/NHS-CLT) or tannic acid cross-linked tissue (TA-CLT). Young's modulus revealed that EDC/NHS-CLT had mechanical properties similar to the native lung and culture of lung mesenchymal cells showed a higher potential of cell proliferation on EDC/NHS-CLT versus TA-CLT and ALT. The in vitro immunogenicity tests showed a strong induction of T-cell proliferation by TA-CLT and an attenuated macrophage induction by TA-CLT. Processed rat lungs were implanted xenogenically into the mouse peritoneal cavity and the host-implant interactions showed that tannic acid is not released from TA-CLT in a physiologically effective dose. The profile of peritoneal fluid proinflammatory (TNFα, IL-1β, IL-12p70 and IL-17) and anti-inflammatory (IL-10 and TGFβ1) cytokines, and CD3 T-lymphocytes and CD11b macrophages revealed that apart from induction of high levels of IL-17 during the first week and IL-10 during the second to third weeks after implantation by TA-CLT, other indicators of immune reactions to cross-linked tissues were not significantly different from ALT. Also, a high fibrotic reaction to TA-CLT was observed on the weeks 2-3, but alveolar structures were preserved in EDC/NHS-CLT. Our findings show that by controlled EDC/NHS cross-linking, an acellular lung scaffold could be provided with mechanical properties similar to native lung, which promotes mesenchymal lung cells proliferation and does not stimulate recipient's immune system more than a non-cross-linked tissue.
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http://dx.doi.org/10.1016/j.msec.2021.111938DOI Listing
March 2021

PLGA/TiO nanocomposite scaffolds for biomedical applications: fabrication, photocatalytic, and antibacterial properties.

Bioimpacts 2021 27;11(1):45-52. Epub 2020 May 27.

Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.

Porous 3D scaffolds synthesized using biocompatible and biodegradable materials could provide suitable microenvironment and mechanical support for optimal cell growth and function. The effect of the scaffold porosity on the mechanical properties, as well as the TiO nanoparticles addition on the bioactivity, antimicrobial, photocatalytic, and cytotoxicity properties of scaffolds were investigated. In the present study, porous scaffolds consisting poly (lactide-co-glycolide) (PLGA) containing TiO nanoparticles were fabricated via air-liquid foaming technique, which is a novel method and has more advantages due to not using additives for nucleation compared to former ways. Adjustment of the foaming process parameters was demonstrated to allow for textural control of the resulting scaffolds and their pore size tuning in the range of 200-600 μm. Mechanical properties of the scaffolds, in particular, their compressive strength, revealed an inverse relationship with the pore size, and varied in the range of 0.97-0.75 MPa. The scaffold with the pore size 270 μm, compressive strength 0.97 MPa, and porosity level 90%, was chosen as the optimum case for the bone tissue engineering (BTE) application. Furthermore, 99% antibacterial effect of the PLGA/10 wt.% TiO nanocomposite scaffolds against the strain was achieved using Escherichia coli. Besides, no negative effect of the new method was observed on the bioactivity behavior and apatite forming ability of scaffolds in the simulated body fluid (SBF). This nanocomposite also displayed a good cytocompatibility when assayed with MG 63 cells. Lastly, the nanocomposite scaffolds revealed the capability to degrade methylene blue (MB) dye by nearly 90% under the UV irradiation for 3 hours. Based on the results, nanocomposite new scaffolds are proposed as a promising candidate for the BTE applications as a replacement for the previous ones.
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http://dx.doi.org/10.34172/bi.2021.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803922PMC
May 2020

Mineralized Human Amniotic Membrane as a Biomimetic Scaffold for Hard Tissue Engineering Applications.

ACS Biomater Sci Eng 2020 Nov 19;6(11):6285-6298. Epub 2020 Oct 19.

Cellular and Molecular Research Center, Iran University of Medical Sciences 1449614535, Tehran, Iran.

The human amniotic membrane (HAM) has been viewed as a potential regenerative material for a wide variety of injured tissues because of its collagen-rich content. High degradability of HAM limits its wide practical application in bone tissue engineering. In this study, the natural matrix of the decellularized amniotic membrane was developed by the double diffusion method. The results confirmed a reduction of the amniotic membrane's degradability because of the deposition of calcium and phosphate ions during the double diffusion process. Real-time PCR results showed a high expression of osteogenesis-related genes from adipose-derived mesenchymal stem cells (ADMSCs) cultured on the surface of the developed mineralized amniotic membrane (MAM). Further experiments were conducted using an MAM preseeded with ADMSCs and a critical-size rat calvarial defect model. Histopathological results confirmed that the MAM + cell sample has excellent potential in bone regeneration.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00881DOI Listing
November 2020

Preparation of internally-crosslinked alginate microspheres: Optimization of process parameters and study of pH-responsive behaviors.

Carbohydr Polym 2021 Mar 5;255:117336. Epub 2020 Nov 5.

Nanotechnology and Regenerative Medicine Centre (Ltd), London BioScience Innovation Centre, London, United Kingdom.

In this study, the effects of various parameters of the water-in-oil emulsification/internal gelation method on the properties of calcium-alginate microparticles were evaluated and optimized. Results showed that the spherical-shaped microparticles with the highest circularity and high production yield can be produced by alginate solution with a concentration of 2 wt.%, calcium carbonate/alginate ratio of 10/1 (w/w), water/oil volume ratio of 1/20, emulsifier concentration of 5 % (v/v), and emulsification speed of 1000 rpm. Two model drugs including simvastatin lactone and simvastatin β-hydroxyacid were loaded into the microspheres with promising encapsulation efficiencies of 73 % and 69 %, respectively. The microspheres showed a pH-responsive swelling behavior with a percentage of 10.60 %, 352.65 %, 690.03 %, and 1211.46 % at the pH values of 2.0, 4.5, 7.4, and 8.5, respectively. The microspheres showed an increasing trend of release rate in direct proportion to pH. These findings would be useful for therapeutic applications which need pH-responsive drug carriers.
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http://dx.doi.org/10.1016/j.carbpol.2020.117336DOI Listing
March 2021

Nanofibrillated chitosan coated highly ordered titania nanotubes array/graphene nanocomposite with improved biological characters.

Carbohydr Polym 2021 Feb 1;254:117465. Epub 2020 Dec 1.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, P.O. Box 14496-14535, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, P.O. Box 14496-14535, Tehran, Iran.

Designing multifunctional surfaces is key to develop advanced materials for orthopedic applications. In this study, we design a double-layer coating, assembled onto the completely regular titania nanotubes (cRTNT) array. Benefiting from the biological and topological characteristics of chitosan nanofibers (CH) and reduced graphene oxide (RGO) through a unique assembly, the designed material features promoted osteoblast cell viability, prolonged antibiotic release profile, as well as inhibited bacterial biofilm formation. The synergistic effect of RGO and CH on the biological performance of the surface is investigatSed. The unique morphology of the nanofibers leads to the partial coverage of RGO-modified nanotubes, providing an opportunity to access the sublayer properties. Another merit of this coating lies in its morphological similarity to the extracellular matrix (ECM) to boost cellular performance. According to the results of this study, this platform holds promising advantages over the bare and bulk biopolymer-modified TNTs.
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http://dx.doi.org/10.1016/j.carbpol.2020.117465DOI Listing
February 2021

Erratum to 'Silk fibroin for skin injury repair: Where do things stand?'. [Advanced Drug Delivery Reviews 153 (2020) 28-53].

Adv Drug Deliv Rev 2020 ;161-162:190-196

Department of Biotechnology, Indian Institute of Technology Kharagpur, India; 3Bs Research Group, I3Bs - Research Institute on Biomaterials, Biodegradable and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Guimaraes, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.addr.2020.11.013DOI Listing
January 2020

Design and fabrication of polycaprolactone/gelatin composite scaffolds for diaphragmatic muscle reconstruction.

J Tissue Eng Regen Med 2021 Jan 28;15(1):78-87. Epub 2020 Nov 28.

Cellular and Molecular Research Center (CMRC), Iran University of Medical Sciences (IUMS), Tehran, Iran.

Diaphragmatic wall defects caused by congenital disorders or disease remain a major challenge for physicians worldwide. Polymeric patches have been extensively explored within research laboratories and the clinic for soft tissue and diaphragm reconstruction. However, patch usage may be associated with allergic reaction, infection, granulation, and recurrence of the hernia. In this study, we designed and fabricated a porous scaffold using a combination of 3D printing and freeze-drying techniques. A 3D printed polycaprolactone (PCL) mesh was used to reinforcegelatin scaffolds, representing an advantage over previously reported examples since it provides mechanical strength and flexibility. In vitro studies showed that adherent cells were anchorage-dependent and grew as a monolayer attached to the scaffolds. Microscopic observations indicated better cell attachments for the scaffolds with higher gelatin content as compared with the PCL control samples. Tensile testing demonstrated the mechanical strength of samples was significantly greater than adult diaphragm tissue. The biocompatibility of the specimens was investigated in vivo using a subcutaneous implantation method in Bagg albino adult mice for 20 days, with the results indicating superior cellular behavior and attachment on scaffolds containing gelatin in comparison to pure PCL scaffolds, suggesting that the porous PCL/gelatin scaffolds have potential as biodegradable and flexible constructs for diaphragm reconstruction.
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http://dx.doi.org/10.1002/term.3151DOI Listing
January 2021

Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel.

Stem Cell Res Ther 2020 10 9;11(1):436. Epub 2020 Oct 9.

Department of Tissue engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Mesenchymal stem cells are a promising cell source for chondrogenic differentiation and have been widely used in several preclinical and clinical studies. However, they are prone to an unwanted differentiation process towards hypertrophy that limits their therapeutic efficacy. Matrix metallopeptidase 13 (MMP-13) is a well-known factor regulated during this undesirable event. MMP-13 is a collagen degrading enzyme, which is also highly expressed in the hypertrophic zone of the growth plate and in OA cartilage. Accordingly, we investigated the effect of MMP-13 inhibition on MSC hypertrophy.

Methods: In this study, 5-bromoindole-2-carboxylic acid (BICA) was used as an inhibitory agent for MMP-13 expression. After identifying its optimal concentration, BICA was mixed into a hydrogel and the release rate was studied. To prepare the ideal hydrogel, chondroitin sulfate (CS) and platelet lysate (PL) were mixed with sodium alginate (Alg) at concentrations selected based on synergistic mechanical and rheometric properties. Then, four hydrogels were prepared by combining alginate (1.5%w/v) and/or CS (1%w/v) and/or PL (20%v/v). The chondrogenic potential and progression to hypertrophy of human bone marrow-derived mesenchymal stem cell (hBM-MSC)-loaded hydrogels were investigated under free swelling and mechanical loading conditions, in the presence and absence of BICA.

Results: Viability of hBM-MSCs seeded in the four hydrogels was similar. qRT-PCR revealed that BICA could successfully inhibit MMP-13 expression, which led to an inhibition of Coll X and induction of Coll-II, in both free swelling and loading conditions. The GAG deposition was higher in the group combining BICA and mechanical stimulation.

Conclusions: It is concluded that BICA inhibition of MMP-13 reduces MSC hypertrophy during chondrogenesis.
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http://dx.doi.org/10.1186/s13287-020-01930-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545577PMC
October 2020

Improvement, scaling-up, and downstream analysis of exosome production.

Crit Rev Biotechnol 2020 Dec 9;40(8):1098-1112. Epub 2020 Aug 9.

Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.

Exosomes are the most researched extracellular vesicles. In many biological, physiological, and pathological studies, they have been identified as suitable candidates for treatment and diagnosis of diseases by acting as the carriers of both drugs and genes. Considerable success has been achieved regarding the use of exosomes for tissue regeneration, cancer diagnosis, and targeted drug/gene delivery to specific tissues. While major progress has been made in exosome extraction and purification, extraction of large quantities of exosomes is still a major challenge. This issue limits the scope of both exosome-based research and therapeutic development. In this review, we have aimed to summarize experimental studies focused at increasing the number of exosomes. Biotechnological studies aimed at identifying the pathways of exosome biogenesis to manipulate some genes in order to increase the production of exosomes. Generally, two major strategies are employed to increase the production of exosomes. First, oogenesis pathways are genetically manipulated to overexpress activator genes of exosome biogenesis and downregulate the genes involved in exosome recycling pathways. Second, manipulation of the cell culture medium, treatment with specific drugs, and limiting certain conditions can force the cell to produce more exosomes. In this study, we have reviewed and categorized these strategies. It is hoped that the information presented in this review will provide a better understanding for expanding biotechnological approaches in exosome-based therapeutic development.
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http://dx.doi.org/10.1080/07388551.2020.1805406DOI Listing
December 2020

Designer Exosomes: A New Platform for Biotechnology Therapeutics.

BioDrugs 2020 Oct;34(5):567-586

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Desirable features of exosomes have made them a suitable manipulative platform for biomedical applications, including targeted drug delivery, gene therapy, cancer diagnosis and therapy, development of vaccines, and tissue regeneration. Although natural exosomes have various potentials, their clinical application is associated with some inherent limitations. Recently, these limitations inspired various attempts to engineer exosomes and develop designer exosomes. Mostly, designer exosomes are being developed to overcome the natural limitations of exosomes for targeted delivery of drugs and functional molecules to wounds, neurons, and the cardiovascular system for healing of damage. In this review, we summarize the possible improvements of natural exosomes by means of two main approaches: parental cell-based or pre-isolation exosome engineering and direct or post-isolation exosome engineering. Parental cell-based engineering methods use genetic engineering for loading of therapeutic molecules into the lumen or displaying them on the surface of exosomes. On the other hand, the post-isolation exosome engineering approach uses several chemical and mechanical methods including click chemistry, cloaking, bio-conjugation, sonication, extrusion, and electroporation. This review focuses on the latest research, mostly aimed at the development of designer exosomes using parental cell-based engineering and their application in cancer treatment and regenerative medicine.
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http://dx.doi.org/10.1007/s40259-020-00434-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402079PMC
October 2020

A novel pathway to produce biodegradable and bioactive PLGA/TiO nanocomposite scaffolds for tissue engineering: Air-liquid foaming.

J Biomed Mater Res A 2020 06 6;108(6):1390-1407. Epub 2020 Mar 6.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Poly (lactate-co-glycolate) (PLGA) is a typical biocompatible and biodegradable synthetic polymer. The addition of TiO nanoparticles has shown to improve compressive modulus of PLGA scaffolds and reduced fast degradation. A novel method has been applied to fabricate PLGA/TiO scaffolds without using any inorganic solvent, with aim of improving the biocompatibility, macroscale morphology, and well inter-connected pores efficacy: Air-Liquid Foaming. Field Emission Scanning Electron Microscopy (FESEM) revealed an increase in interconnected porosity of up to 98%. As well the compressive testing showed enhancement in modulus. Bioactivity and in vitro degradation were studied with immersion of scaffolds in Simulated Body Fluid (SBF) and incubation in Phosphate Buffered Saline (PBS), respectively. Formation of apatite layer corroborated the bioactivity after soaking in SBF. Degradation rate of scaffolds was increased with excessive addition of TiO contents withal. The in vitro cultured human-like MG63 ostoblast cells showed attachment, proliferation, and nontoxcitiy in contact, using MTT assay [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide]. According to the results, the novel method utilized in this study generated porous viable tissue without using any inorganic solvent or porogen can be a promising candidate in further treatment of orthopedic patients effectively.
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http://dx.doi.org/10.1002/jbm.a.36910DOI Listing
June 2020

The in vivo effect of Lacto-N-neotetraose (LNnT) on the expression of type 2 immune response involved genes in the wound healing process.

Sci Rep 2020 01 22;10(1):997. Epub 2020 Jan 22.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Lacto-n-neotatraose (LNnT) oligosaccharide shows properties such as anti-inflammatory, type 2 immune response induction, induced angiogenesis, and anti-bacterial effects. Here, we hypothesized that the application of LnNT in the skin full-thickness wound can accelerate the healing process through its anti-inflammatory effect as well as induction of type 2 immune responses. In this study, we evaluated the cell viability of fibroblasts in the presence of LNnT. The full-thickness wound model was created by punch biopsy. The mice were treated intradermaly with LNnT at the concentrations of 100 and 200 µg or PBS as a control group. The wounds samples were compared based on the macroscopic and histological evaluations. The amount of collagen deposition and expression of genes involved in type 2 immunity were measured by the hydroxyproline assay and real time PCR method, respectively. Our results showed that LNnT had no negative effect on the cell viability of fibroblasts. LNnT increased the wound closure rate on day 7 post-wounding. H&E stain analysis revealed that mice treated with 200 µg LNnT exhibited better healing score, follicle formation, and lower epidermal thickness index. The mice treated with LNnT exhibited a lower collagen deposition on day 21 and higher collagen content on days 7 and 14 post-treatment. The LNnT groups also exhibited a lower number of neutrophils and a higher number of basal cells and fibroblasts. The expression rate of IL-10, IL-4, and IL-13 was higher in the LNnT groups. These results showed the high potential of LNnT for use in treatment of full-thickness wounds.
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http://dx.doi.org/10.1038/s41598-020-57860-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976585PMC
January 2020

Tenocyte-imprinted substrate: a topography-based inducer for tenogenic differentiation in adipose tissue-derived mesenchymal stem cells.

Biomed Mater 2020 04 16;15(3):035014. Epub 2020 Apr 16.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Tendon tissue engineering based on stem cell differentiation has attracted a great deal of attention in recent years. Previous studies have examined the effect of cell-imprinted polydimethylsiloxane (PDMS) substrate on induction differentiation in stem cells. In this study, we used tenocyte morphology as a positive mold to create a tenocyte-imprinted substrate on PDMS. The morphology and topography of this tenocyte replica on PDMS was evaluated with scanning electron microscopy (SEM) and atomic force microscopy. The tenogenic differentiation induction capacity of the tenocyte replica in adipose tissue-derived mesenchymal stem cells (ADSCs) was then investigated and compared with other groups, including tissue replica (which was produced similarly to the tenocyte replica and was evaluated by SEM), decellularized tendon, and bone morphogenic protein (BMP)-12, as other potential inducers. This comparison gives us an estimate of the ability of tenocyte-imprinted PDMS (called cell replica in the present study) to induce differentiation compared to other inducers. For this reason, ADSCs were divided into five groups, including control, cell replica, tissue replica, decellularized tendon and BMP-12. ADSCs were seeded on each group separately and investigated by the real-time reverse transcription polymerase chain reaction (RT-PCR) technique after seven and 14 days. Our results showed that in spite of the higher effect of the growth factor on tenogenic differentiation, the cell replica can also induce tenocyte marker expression (scleraxis and tenomodulin) in ADSCs. Moreover, the tenogenic differentiation induction capacity of the cell replica was greater than tissue replica. Immunocytochemistry analysis revealed that ADSCs seeding on the cell replica for 14 days led to scleraxis and tenomodulin expression at the protein level. In addition, immunohistochemistry indicated that contrary to the promising results in vitro, there was little difference between ADSCs cultured on tenocyte-imprinted PDMS and untreated ADSCs. The results of such studies could lead to the production of inexpensive cell culture plates or biomaterials that can induce differentiation in stem cells without growth factors or other supplements.
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http://dx.doi.org/10.1088/1748-605X/ab6709DOI Listing
April 2020

Silk fibroin for skin injury repair: Where do things stand?

Adv Drug Deliv Rev 2020 01 31;153:28-53. Epub 2019 Oct 31.

Department of Biotechnology, Indian Institute of Technology Kharagpur, India; 3Bs Research Group, I3Bs - Research Institute on Biomaterials, Biodegradable and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Guimaraes, Portugal. Electronic address:

Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed. STATEMENT OF SIGNIFICANCE: Silk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications.
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http://dx.doi.org/10.1016/j.addr.2019.09.003DOI Listing
January 2020

Inducing type 2 immune response, induction of angiogenesis, and anti-bacterial and anti-inflammatory properties make Lacto-n-Neotetraose (LNnT) a therapeutic choice to accelerate the wound healing process.

Med Hypotheses 2020 Jan 3;134:109389. Epub 2019 Sep 3.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The healing process of non-healing and full-thickness wounds is currently facing some serious challenges. In such ulcers, losing a large part of skin causes a chronic infection due to the entrance of various pathogens in the wound bed. Moreover, poor vascularization, uncontrolled inflammation, and delayed re-epithelialization increase the healing time in patients suffering from such wounds. In this light, tissue engineering provides a wide range of strategies using a variety of biomaterials, biofactors and stem cells to decrease the healing time and restore the function of the damaged site. A suitable wound healing agent should possess some critical parameters such as inducing re-epithelialization, anti-inflammatory and anti-bacterial properties, and angiogenic capability. The Lacto-n-Neotetraose (LNnT) with chemical formula C26H45NO21 is an oligosaccharide present in human milk and soluble antigens extracted from Schistosoma mansoni eggs. It is reported that LNnT induces type 2 immune response (Th2 immunity). Th2 immunity promotes re-epithelialization, angiogenesis and wound contraction by recruiting the cells which produce Th2-related cytokines. Moreover, LNnT shows some special characteristics such as angiogenic capability, anti-inflammatory, and anti-bacterial effects which can address the mentioned challenges in the treatment of non-healing and full-thickness wounds. Here, we hypothesize that utilizing LNnT is an appropriate biofactor which would improve the healing process in full-thickness and non-healing wounds.
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http://dx.doi.org/10.1016/j.mehy.2019.109389DOI Listing
January 2020

Decellularization and preservation of human skin: A platform for tissue engineering and reconstructive surgery.

Methods 2020 01 11;171:62-67. Epub 2019 Jul 11.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Institute of Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

A matrix derived from natural tissue functions as a highly biocompatible and versatile scaffold for tissue engineering applications. It can act as a supportive construct that provides a niche for colonization by host cells. In this work, we describe a cost-effective, reliable and reproducible protocol for decellularization and preservation of human skin as a potential soft tissue replacement. The decellularized human skin is achieved using purely chemical agents without any enzymatic steps. The suitability of the proposed method for the preservation of the extracellular matrix (ECM) structure and its main components and integrity were evaluated using histological and immunohistochemical analysis. Cryopreservation and final sterility were conducted using programmable freeze-drying and gamma irradiation. The architecture, basement membrane and 3D structure of ECM can be successfully preserved after decellularization. Our protocol was found to be appropriate to maintain key proteins such as collagen type I, III, IV and laminin in the structure of final scaffold. This protocol offers a novel platform for the preparation of a dermal substitute for potential clinical applications. STATEMENT OF SIGNIFICANCE: Clinical application of naturally-based scaffolds for verity of health problems obliges development of a reproducible and effective technology that does not change structural and compositional material properties during scaffold preparation and preservation. Lack of an effective protocol for the production of biological products using decellularization method is still remaining. This effort is directing to solve this challenge in order to accomplish the off-the -shelf availability of decellularized dermal scaffold in market for clinical application.
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http://dx.doi.org/10.1016/j.ymeth.2019.07.005DOI Listing
January 2020

The relationship between molecular content of mesenchymal stem cells derived exosomes and their potentials: Opening the way for exosomes based therapeutics.

Biochimie 2019 Oct 11;165:76-89. Epub 2019 Jul 11.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

At least, more than half of our understanding of extracellular vesicles owes to the studies conducted over the past few years. When it became clear that the exosomes have various potentials in medicine, extensive research has focused on these potentials in a variety of areas including cancer, drug delivery and regenerative medicine. The growing understanding of molecular structure and functions of exosomes causes the vision to become brighter in the exosomes complexity, and our attitude toward these vesicles has undergone changes accordingly. Proteomic and transcriptomic studies on exosomes have highlighted their molecular diversity. In this review, we explicitly examine the exosomes composition, molecular structure and their therapeutic potentials in some diseases. Due to the very heterogeneous nature of exosomes, the process of their use as a therapeutic agent in the clinic has been challenged. We are still at the beginning of recognizing the molecular composition of exosomes and mechanisms that affect their physiology and biology. The growing trend of engineering of exosomes has shown a promising future to further utilize them in a different field. Molecular profiling of exosomes and their content for their related potentials in regenerative medicine should be done exactly for further defining a minimum content for specific therapeutic potentials.
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http://dx.doi.org/10.1016/j.biochi.2019.07.009DOI Listing
October 2019

The Effect of Alpha-Tocopherol on Morphine Tolerance-induced Expression of c-fos Proto-oncogene from a Biotechnological Perspective.

Recent Pat Biotechnol 2019 ;13(2):137-148

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: The increase of oxidant compounds is the most well-known reasons for the tolerance to the analgesic properties of Morphine. Additionally, the production of proxy-nitrite impairs receptors, proteins and enzymes involved in the signaling pathways of analgesia, apoptosis and necrosis. Also, we revised all patents relating to opioid tolerance control methods.

Objective: The aim of this study was to assess the effects of Alpha-tocopherol as an anti-oxidant agent to reduce Morphine tolerance.

Method: Forty male rats randomly divided into four groups. 10 mg/kg of morphine was injected subcutaneously to create the desired level of tolerance. After modeling, 70 mg/kg Alpha- Tocopherol was injected intraperitoneal. Also, the hot plate recorded pain threshold alterations was used to evaluate the behavioral test. All tissue samples were extracted from the spinal cord, thalamus and frontal cortex for molecular and gene expression evaluations. Also, the effect of Alpha- Tocopherol on the apoptosis and necrosis parameters was analyzed using nissl staining and tunel test.

Results: The time latency results showed that there were no significant differences in the different days in groups treated with Morphine plus Alpha-Tocopherol. However, our data highlighted that the pain threshold and their time latency in respond to it had substantially increased in comparison with the control group. Furthermore, we found that the Alpha-Tocopherol obviously decreased c-fos gene expression, especially in the spinal cord.

Conclusion: Thus, co-administration of Alpha-Tocopherol with Morphine can decrease the adverse effects of nitrite proxy, which is released due to repeated injections of Morphine.
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http://dx.doi.org/10.2174/1872208312666181120105333DOI Listing
June 2019

Modulation of Hypertrophic Scar Formation Using Amniotic Membrane/Electrospun Silk Fibroin Bilayer Membrane in a Rabbit Ear Model.

ACS Biomater Sci Eng 2019 Mar 14;5(3):1487-1496. Epub 2019 Feb 14.

3Bs Research Group, I3Bs-Institute on Biomaterials, biodegradables and Biomimetics. Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, AvePark, Barco, Guimaraes 4805-017, Portugal.

Hypertrophic scarring is a dermal disorder resulting from collagen and other extra cellular matrix protein depositions following the deep trauma, severe burn injury, and surgery incisions. A variety of therapeutic procedures are currently available, however, achieving an ideal treatment method remains a challenge. In our recently published report, a 3D bilayered decellularized human amniotic membrane/electrospun silk fibroin membrane was fabricated and characterized for regenerative medical applications. To obtain a solid bind between two layers, the samples were immersed in 70% ethanol. In this study, the effects of amniotic membrane/electrospun silk fibroin on minimizing the postinjury hypertrophic scar formation were determined in the rabbit ear model. In vivo experiments were carried out to assess the bilayer membrane characteristics on full thickness hypertrophic scar at days 28 and 50 postimplantations. A significant decrease in collagen deposition and expression and increased expression and deposition of MMP1 in the wound bed were observed on the wounds dressed with bilayered membrane when compared to the amniotic membrane alone and controls (wound with no implant). The current study shows that our fabricated construct has potential as an efficient antiscarring wound dressing material and may also serve for the subsequent soft tissue engineering needs.
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http://dx.doi.org/10.1021/acsbiomaterials.8b01521DOI Listing
March 2019

Nanocomposite scaffold seeded with mesenchymal stem cells for bone repair.

Cell Biol Int 2019 Feb 27. Epub 2019 Feb 27.

Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.

The mechanical property of bone tissue scaffolds is one of the most important aspects in bone tissue engineering that has remained problematic. In our previous study, we fabricated a three-dimensional scaffold from nano-hydroxyapatite/gelatin (nHA/Gel) and investigated its efficiency in promoting bone regeneration both in vitro and in vivo. In the present study, the effect of adding silicon carbide (SiC) on the mechanical and biological behaviors of the nHA/Gel/SiC and bone regeneration in vivo were determined. nHA and SiC were synthesized and characterized by the X-ray diffraction pattern and transmission electron microscope image. Layer solvent casting, freeze drying, and lamination techniques were applied to prepare these scaffolds. Then, the biocompatibility and cell adhesion behavior of the synthesized nHA/Gel/SiC scaffolds were investigated. For in vivo studies, rats were categorized into three groups: blank defect, blank scaffold, and rat bone marrow mesenchymal stem cells (rBM-MSCs)/scaffold. After 1, 4, and 12 weeks post-injury, the rats were sacrificed and the calvaria were harvested. Sections with a thickness of 5 µm thickness were prepared and stained with hematoxylin-eosin and Masson's Trichrome, and immunohistochemistry was performed. Our results showed that SiC effectively increased the mechanical properties of the nHA/Gel/SiC scaffold. No significant differences were observed in biocompatibility, cell adhesion, and cytotoxicity of the nHA/Gel/SiC in comparison with the nHA/Gel nanocomposite. Based on histological and immunohistochemical studies, both osteogenesis and collagenization were significantly higher in the rBM-MSCs/scaffold group, quantitatively and qualitatively. The present study strongly suggests the potential of SiC as an alternative strategy to improve the mechanical and biological properties of bone tissue engineering scaffolds, and shows that the pre-seeded nHA/Gel/SiC scaffold with rBM-MSCs improves osteogenesis in the engineered bone implant.
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http://dx.doi.org/10.1002/cbin.11124DOI Listing
February 2019

Hybrid and Composite Scaffolds Based on Extracellular Matrices for Cartilage Tissue Engineering.

Tissue Eng Part B Rev 2019 06;25(3):202-224

1 Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Impact Statement: Scaffolds fabricated from extracellular matrix (ECM) derivatives are composed of conducive structures for cell attachment, proliferation, and differentiation, but generally do not have proper mechanical properties and load-bearing capacity. In contrast, scaffolds based on synthetic biomaterials demonstrate appropriate mechanical strength, but the absence of desirable biological properties is one of their main disadvantages. To integrate mechanical strength and biological cues, these ECM derivatives can be conjugated with synthetic biomaterials. Hence, hybrid scaffolds comprising both advantages of synthetic polymers and ECM derivatives can be considered a robust vehicle for tissue engineering applications.
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http://dx.doi.org/10.1089/ten.TEB.2018.0245DOI Listing
June 2019

Poly (ɛ-caprolactone)-chitosan-poly (vinyl alcohol) nanofibrous scaffolds for skin excisional and burn wounds in a canine model.

IET Nanobiotechnol 2018 08;12(5):619-625

Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran 144961-4535, Iran.

Poly (ɛ-caprolactone)-chitosan-poly (vinyl alcohol) (PCL: Cs: PVA) nanofibrous blend scaffolds were known as useful materials for skin wound healing and would help the healing process about 50% faster at the final time point. From the previous studies by the authors, PCL: Cs: PVA (in 2: 1: 1.5 mass ratio) nanofibres showed high efficacy in healing on rat models. In this study, the scaffolds were examined in burn and excision wounds healing on dogs as bigger models. The scaffolds were applied on dorsum skin wounds ( = 5) then macroscopic and microscopic investigations were carried out to measure the wounds areas and to track healing rate, respectively. Macroscopic results showed good aspect healing effect of scaffolds compared with control wounds especially after 21 days post-operating for both cutting and burn wounds. Pathological studies showed that the healing rates of the wounds covered with PCL: Cs: PVA nanofibrous scaffolds were much rapid compared to untreated wounds in control group. The immunogenicity of the scaffolds in canine model was also investigated. The findings showed that nanofibrous blend scaffolds was not immunogenic in humoural immune responses. All these results indicated that PCL: Cs: PVA nanofibrous web could be considered as promising materials for wounds healings.
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http://dx.doi.org/10.1049/iet-nbt.2017.0115DOI Listing
August 2018

Corrigendum to "A new rat model of neonatal bilirubin encephalopathy (kernicterus)" [J. Pharmacol. Toxicol. Methods 84 (2017) 44-50].

J Pharmacol Toxicol Methods 2018 Jul - Aug;92:95. Epub 2018 Mar 11.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.vascn.2018.02.006DOI Listing
March 2018

3D Protein-Based Bilayer Artificial Skin for the Guided Scarless Healing of Third-Degree Burn Wounds in Vivo.

Biomacromolecules 2018 07 18;19(7):2409-2422. Epub 2018 Apr 18.

3Bs Research Group, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , University of Minho , 4805-017 Barco, Guimaraes , Portugal.

Severe burn injuries can lead to delays in healing and devastating scar formation. Attempts have been made to develop a suitable skin substitute for the scarless healing of such skin wounds. Currently, there is no effective strategy for completely scarless healing after the thermal injuries. In our recent work, we fabricated and evaluated a 3D protein-based artificial skin made from decellularized human amniotic membrane (AM) and electrospun nanofibrous silk fibroin (ESF) in vitro. We also characterized both biophysical and cell culture investigation to establish in vitro performance of the developed bilayer scaffolds. In this report, we evaluate the appropriate utility of this fabricated bilayered artificial skin in vivo with particular emphasis on healing and scar formation due to the biochemical and biomechanical complexity of the skin. For this work, AM and AM/ESF membranes alone or seeded with adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are implanted on full-thickness burn wounds in mice. The healing efficacy and scar formation are evaluated at 7, 14, and 28 days post-implantation in vivo. Our data reveal that ESF accelerates the wound-healing process through the early recruitment of inflammatory cells such as macrophages into the defective site as well as the up-regulation of angiogenic factors from the AT-MSCs and the facilitation of the remodeling phase. In vivo application of the prepared AM/ESF membrane seeded with the AT-MSCs reduces significantly the post-burn scars. The in vivo data suggest that the potential applications of the AM/ESF bilayered artificial skin may be considered a clinical translational product with stem cells to guide the scarless healing of severe burn injuries.
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http://dx.doi.org/10.1021/acs.biomac.7b01807DOI Listing
July 2018

A Comparative Study of Rat Lung Decellularization by Chemical Detergents for Lung Tissue Engineering.

Open Access Maced J Med Sci 2017 Dec 6;5(7):859-865. Epub 2017 Dec 6.

Division of Tissue Engineering and Regenerative Medicine, Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Background: Lung disease is the most common cause of death in the world. The last stage of pulmonary diseases is lung transplantation. Limitation and shortage of donor organs cause to appear tissue engineering field. Decellularization is a hope for producing intact ECM in the development of engineered organs.

Aim: The goal of the decellularization process is to remove cellular and nuclear material while retaining lung three-dimensional and molecular proteins. Different concentration of detergents was used for finding the best approach in lung decellularization.

Material And Methods: In this study, three-time approaches (24, 48 and 96 h) with four detergents (CHAPS, SDS, SDC and Triton X-100) were used for decellularizing rat lungs for maintaining of three-dimensional lung architecture and ECM protein composition which have significant roles in differentiation and migration of stem cells. This comparative study determined that variable decellularization approaches can cause significantly different effects on decellularized lungs.

Results: Results showed that destruction was increased with increasing the detergent concentration. Single detergent showed a significant reduction in maintaining of three-dimensional of lung and ECM proteins (Collagen and Elastin). But, the best methods were mixed detergents of SDC and CHAPS in low concentration in 48 and 96 h decellularization.

Conclusion: Decellularized lung tissue can be used in the laboratory to study various aspects of pulmonary biology and physiology and also, these results can be used in the continued improvement of engineered lung tissue.
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http://dx.doi.org/10.3889/oamjms.2017.179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771286PMC
December 2017

Silk fibroin/amniotic membrane 3D bi-layered artificial skin.

Biomed Mater 2018 02 20;13(3):035003. Epub 2018 Feb 20.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Cellular & Molecular Biology Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.

Burn injuries have been reported to be an important cause of morbidity and mortality and they are still considered as unmet clinical need. Although there is a myriad of effective stem cells that have been suggested for skin regeneration, there is no one ideal scaffold. The aim of this study was to develop a three-dimensional (3D) bi-layer scaffold made of biological decellularized human amniotic membrane (AM) with viscoelastic electrospun nanofibrous silk fibroin (ESF) spun on top. The fabricated 3D bi-layer AM/ESF scaffold was submerged in ethanol to induce β-sheet transformation as well as to get a tightly coated and inseparable bi-layer. The biomechanical and biological properties of the 3D bi-layer AM/ESF scaffold were investigated. The results indicate significantly improved mechanical properties of the AM/ESF compared with the AM alone. Both the AM and AM/ESF possess a variety of suitable adhesion cells without detectable cytotoxicity against adipose tissue-derived mesenchymal stem cells (AT-MSCs). The AT-MSCs show increased expression of two main pro-angiogenesis factors, vascular endothelial growth factor and basic fibroblast growth factor, when cultured on the AM/ESF for 7 days, when comparing with AM alone. The results suggest that the AM/ESF scaffold with autologous AT-MSCs has excellent cell adhesion and proliferation along with production of growth factors which serves as a possible application in a clinical setting for skin regeneration.
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http://dx.doi.org/10.1088/1748-605X/aa999bDOI Listing
February 2018

Novel fluoridated silk fibroin/ TiO nanocomposite scaffolds for bone tissue engineering.

Mater Sci Eng C Mater Biol Appl 2018 Jan 4;82:265-276. Epub 2017 Sep 4.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran.

It is known that Fluoride ions strongly affect bone mineralization and formation. In the present study, the engineered bone tissue scaffolds are fabricated using silk fibroin (SF) and flouridated TiO nanoparticles. TiO nanoparticles are modified by fluoride ions, and different levels (0, 5, 10, 15 and 20wt%) of the fluoridated TiO nanoparticles (TiO-F) were subsequently added to the SF matrix through phase separation method to prepare silk fibroin/flouridated TiO nanocomposite scaffolds (SF/TiO-F). Phase structure, functional groups, morphology and mechanical properties of the obtained scaffolds were evaluated by X-ray diffraction method (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and compressive testing, respectively. In vitro degradation studies of scaffolds were performed by incubating the samples in phosphate buffered saline (PBS) at 37°C and pH7.4 for 30days. Additionally, the bioactivity of scaffolds was estimated in a simulated body fluid (SBF) buffered at 37°C and pH7.4 for 28days. Moreover, MTT assay was used to confirm the biocompatibility of the scaffolds using human like SaOS-2 osteoblast cell line for 1, 3 and 5days. The obtained results indicated that the mechanical properties of scaffolds have been improved by increasing the TiO-F amount up to 15wt%. However, a detrimental effect was observed by a further increase in the TiO-F content. The bioactivity of SF/TiO-F nanocomposite scaffolds was promoted by flouridation of TiO. Furthermore, cell cytotoxicity results demonstrated that the SF/TiO-F nanocomposite scaffolds are nontoxic to osteoblasts. The cell fixation results after 3days of incubation revealed that the cell attachment and spreading on SF/TiO-F nanocomposite scaffolds are improved with respect to SF/TiO nanocomposite scaffolds control sample.
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http://dx.doi.org/10.1016/j.msec.2017.09.001DOI Listing
January 2018

Collagen-coated nano-electrospun PCL seeded with human endometrial stem cells for skin tissue engineering applications.

J Biomed Mater Res B Appl Biomater 2018 05 9;106(4):1578-1586. Epub 2017 Aug 9.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Human endometrial stem cells (hEnSCs) are known as an attractive source of stem cells for regenerative medicine. hEnSCs are easily isolated and are capable of repairing uterine through their strong ability of creating new capillaries. In this study, a three-dimensional (3D) nanofibrous polycaprolactone (PCL)/collagen scaffold was fabricated and characterized in order to be applied as a new approach for skin reconstruction. Furthermore, the behavior of hEnSCs on this scaffold was investigated. First, a PCL 3D scaffold was constructed using electrospinning technique. Plasma treated and PCL was grafted by collagen. The constructs were characterized for mechanical and structural properties. Cell attachment, proliferation, viability, and differentiation of hEnSCs were assessed after being seeded on PCL and PCL/collagen scaffolds using scanning electron microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and real-time polymerase chain reaction tests. The results showed higher wettability for the PCL/collagen scaffold with desirable mechanical and structural characteristics compared to PCL and collagen alone. The attachment and proliferation rates of hEnSCs on the PCL/collagen scaffold were higher compared to those on the bare PCL. Hence, hEnSCs are newly discovered stem cell source for skin tissue engineering in vitro, particularly when developed on PCL/collagen nanofiber scaffolds. Therefore, application of hEnSCs for skin regeneration is a novel therapeutic approach for temporary skin substitute. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1578-1586, 2018.
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http://dx.doi.org/10.1002/jbm.b.33966DOI Listing
May 2018

An acid-free water-born quaternized chitosan/montmorillonite loaded into an innovative ultra-fine bead-free water-born nanocomposite nanofibrous scaffold; in vitro and in vivo approaches.

Biomed Mater 2017 Jul 26;12(4):045014. Epub 2017 Jul 26.

Textile Engineering Department, Yazd University, PO Box 89195-741, Yazd, Iran.

An acid-free water-born chitosan derivative/montmorillonite has been successfully synthesized. A natural-based biopolymer, N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride, was synthesized, and its structure confirmed by Fourier transform infrared microscopy and conductometric titration. It was applied to the cationic ion-exchange reaction of montmorillonite. Then, the synthesized materials were used to produce water-born composite scaffolds for tissue engineering applications and formed an ultra-fine bead-free multicomponent nanofibrous scaffold. The scaffold was subjected to in vitro and in vivo investigations. The effects of both acidic and neutral reaction media on the efficiency of the cationic ion-exchange reaction of montmorillonite were investigated. A mechanism has been suggested for the more efficient cationic ion-exchange reaction achieved in the absence of the acid. In in vitro studies, the modified montmorillonite showed synergistic biocompatibility and cell growth with enhanced bioactivity compared to unmodified clay and even chitosan and the chitosan derivative. Scanning electron microscopy showed ultra-fine bead-free nanocomposite nanofibers. Improved biocompatibility, cell attachment, and cell growth were observed for the nanofibrous scaffolds compared to the individual components. In vivo experiments showed complete restoration of a critical-sized full-thickness wound without infection in 21 d. The technique provides a guideline to achieve chitosan nanofibrous morphology for multifunctional biomedical applications.
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http://dx.doi.org/10.1088/1748-605X/aa7608DOI Listing
July 2017

A Dermal Equivalent Engineered with TGF-β3 Expressing Bone Marrow Stromal Cells and Amniotic Membrane: Cosmetic Healing of Full-Thickness Skin Wounds in Rats.

Artif Organs 2016 Dec;40(12):E266-E279

Eposcience Millennium Institute, Tehran, Iran.

Transforming growth factor beta-3 (TGF-β3) has been shown to decrease scar formation after scheduled topical applications to the cutaneous wounds. This study aimed to continuously deliver TGF-β3, during the early phase of wound healing, by engineering a dermal equivalent (DE) using TGF-β3 expressing bone marrow stromal cells (BM-SCs) and human dehydrated amniotic membrane (hDAM). To engineer a DE, rat BM-SCs were seeded on the hDAM and TGF-β3 was transiently transfected into the BM-SCs using a plasmid vector. Pieces of the dermal equivalent were transplanted onto the full-thickness excisional skin wounds in rats. The process of wound healing was assessed by image analysis, Manchester Scar Scale (MSS), and histopathological studies 7, 14, 21, and 85 days after the excision. The results confirmed accurate construction of recombinant pcDNA3.1-TGF-β3 expression system and showed that the transfected BM-SCs seeded on hDAM expressed TGF-β3 mRNA and protein from day 3 through day 7 after transfection. After implantation of the DE, contraction of the wounds was measured from day 7 through 21 and analyzed by linear regression, which revealed that the rate of wound contraction in all experimental groups was similar. Histologic evaluation demonstrated that transfected BM-SCs decreased retention and recruitment of the cells during the early stage of wound healing, decreased the formation of vascular structures and led to formation of uniformly parallel collagen bundles. MSS scores showed that TGF-β3 secreting cells significantly improved the cosmetic appearance of the healed skin and decreased the scar formation. From these results, it could be concluded that transient secretion of TGF-β3, during the early phase of healing, by BM-SCs seeded on hDAM can improve the cosmetic appearance of the scar in cutaneous wounds without negatively affecting the process of wound repair.
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http://dx.doi.org/10.1111/aor.12807DOI Listing
December 2016