Publications by authors named "Khashayar Modaresifar"

11 Publications

  • Page 1 of 1

On the Use of Black Ti as a Bone Substituting Biomaterial: Behind the Scenes of Dual-Functionality.

Small 2021 May 12:e2100706. Epub 2021 May 12.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, Delft, 2628 CD, The Netherlands.

Despite the potential of small-scale pillars of black titanium (bTi) for killing the bacteria and directing the fate of stem cells, not much is known about the effects of the pillars' design parameters on their biological properties. Here, three distinct bTi surfaces are designed and fabricated through dry etching of the titanium, each featuring different pillar designs. The interactions of the surfaces with MC3T3-E1 preosteoblast cells and Staphylococcus aureus bacteria are then investigated. Pillars with different heights and spatial organizations differently influence the morphological characteristics of the cells, including their spreading area, aspect ratio, nucleus area, and cytoskeletal organization. The preferential formation of focal adhesions (FAs) and their size variations also depend on the type of topography. When the pillars are neither fully separated nor extremely tall, the colocalization of actin fibers and FAs as well as an enhanced matrix mineralization are observed. However, the killing efficiency of these pillars against the bacteria is not as high as that of fully separated and tall pillars. This study provides a new perspective on the dual-functionality of bTi surfaces and elucidates how the surface design and fabrication parameters can be used to achieve a surface topography with balanced bactericidal and osteogenic properties.
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http://dx.doi.org/10.1002/smll.202100706DOI Listing
May 2021

Osteogenic and antibacterial surfaces on additively manufactured porous Ti-6Al-4V implants: Combining silver nanoparticles with hydrothermally synthesized HA nanocrystals.

Mater Sci Eng C Mater Biol Appl 2021 Jan 26;120:111745. Epub 2020 Nov 26.

Department of Biomechanical Engineering, Delft University of Technology, Mekelweg 2, 2628 CD Delft, the Netherlands.

The recently developed additively manufacturing techniques have enabled the fabrication of porous biomaterials that mimic the characteristics of the native bone, thereby avoiding stress shielding and facilitating bony ingrowth. However, aseptic loosening and bacterial infection, as the leading causes of implant failure, need to be further addressed through surface biofunctionalization. Here, we used a combination of (1) plasma electrolytic oxidation (PEO) using Ca-, P-, and silver nanoparticle-rich electrolytes and (2) post-PEO hydrothermal treatments (HT) to furnish additively manufactured Ti-6Al-4V porous implants with a multi-functional surface. The applied HT led to the formation of hydroxyapatite (HA) nanocrystals throughout the oxide layer. This process was controlled by the supersaturation of Ca and PO during the hydrothermal process. Initially, the high local supersaturation resulted in homogenous nucleation of spindle-like nanocrystals throughout the surface. As the process continued, the depletion of reactant ions in the outermost surface layer led to a remarkable decrease in the supersaturation degrees. High aspect-ratio nanorods and hexagonal nanopillars were, therefore, created. The unique hierarchical structure of the microporous PEO layer (pore size < 3 μm) and spindle-like HA nanocrystals (<150 nm) on the surface of macro-porous additively manufactured Ti-6Al-4V implants provided a favorable substrate for the anchorage of cytoplasmic extensions assisting cell attachment and migration on the surface. The results of our in vitro assays clearly showed the important benefits of the HT and the spindle-like HA nanocrystals including a significantly stronger and much more sustained antibacterial activity, significantly higher levels of pre-osteoblasts metabolic activity, and significantly higher levels of alkaline phosphatase activity as compared to similar PEO-treated implants lacking the HT.
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http://dx.doi.org/10.1016/j.msec.2020.111745DOI Listing
January 2021

Quantitative mechanics of 3D printed nanopillars interacting with bacterial cells.

Nanoscale 2020 Nov;12(43):21988-22001

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, 2628CD, Delft, The Netherlands.

One of the methods to create sub-10 nm resolution metal-composed 3D nanopillars is electron beam-induced deposition (EBID). Surface nanotopographies (e.g., nanopillars) could play an important role in the design and fabrication of implantable medical devices by preventing the infections that are caused by the bacterial colonization of the implant surface. The mechanical properties of such nanoscale structures can influence their bactericidal efficiency. In addition, these properties are key factors in determining the fate of stem cells. In this study, we quantified the relevant mechanical properties of EBID nanopillars interacting with Staphylococcus aureus (S. aureus) using atomic force microscopy (AFM). We first determined the elastic modulus (17.7 GPa) and the fracture stress (3.0 ± 0.3 GPa) of the nanopillars using the quantitative imaging (QI) mode and contact mode (CM) of AFM. The displacement of the nanopillars interacting with the bacteria cells was measured by scanning electron microscopy (50.3 ± 9.0 nm). Finite element method based simulations were then applied to obtain the force-displacement curve of the nanopillars (considering the specified dimensions and the measured value of the elastic modulus) based on which an interaction force of 88.7 ± 36.1 nN was determined. The maximum von Mises stress of the nanopillars subjected to these forces was also determined (3.2 ± 0.3 GPa). These values were close to the maximum (i.e., fracture) stress of the pillars as measured by AFM, indicating that the nanopillars were close to their breaking point while interacting with S. aureus. These findings reveal unique quantitative data regarding the mechanical properties of nanopillars interacting with bacterial cells and highlight the possibilities of enhancing the bactericidal activity of the investigated EBID nanopillars by adjusting both their geometry and mechanical properties.
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http://dx.doi.org/10.1039/d0nr05984fDOI Listing
November 2020

Deciphering the Roles of Interspace and Controlled Disorder in the Bactericidal Properties of Nanopatterns against .

Nanomaterials (Basel) 2020 Feb 18;10(2). Epub 2020 Feb 18.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, 2628CD Delft, The Netherlands.

Recent progress in nano-/micro-fabrication techniques has paved the way for the emergence of synthetic bactericidal patterned surfaces that are capable of killing the bacteria via mechanical mechanisms. Different design parameters are known to affect the bactericidal activity of nanopatterns. Evaluating the effects of each parameter, isolated from the others, requires systematic studies. Here, we systematically assessed the effects of the interspacing and disordered arrangement of nanopillars on the bactericidal properties of nanopatterned surfaces. Electron beam induced deposition (EBID) was used to additively manufacture nanopatterns with precisely controlled dimensions (i.e., a height of 190 nm, a diameter of 80 nm, and interspaces of 100, 170, 300, and 500 nm) as well as disordered versions of them. The killing efficiency of the nanopatterns against Gram-positive bacteria increased by decreasing the interspace, achieving the highest efficiency of 62 ± 23% on the nanopatterns with 100 nm interspacing. By comparison, the disordered nanopatterns did not influence the killing efficiency significantly, as compared to their ordered correspondents. Direct penetration of nanopatterns into the bacterial cell wall was identified as the killing mechanism according to cross-sectional views, which is consistent with previous studies. The findings indicate that future studies aimed at optimizing the design of nanopatterns should focus on the interspacing as an important parameter affecting the bactericidal properties. In combination with controlled disorder, nanopatterns with contrary effects on bacterial and mammalian cells may be developed.
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http://dx.doi.org/10.3390/nano10020347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075137PMC
February 2020

Reactive ion etching for fabrication of biofunctional titanium nanostructures.

Sci Rep 2019 12 11;9(1):18815. Epub 2019 Dec 11.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, 2628 CD, Delft, The Netherlands.

One of the major problems with the bone implant surfaces after surgery is the competition of host and bacterial cells to adhere to the implant surfaces. To keep the implants safe against implant-associated infections, the implant surface may be decorated with bactericidal nanostructures. Therefore, fabrication of nanostructures on biomaterials is of growing interest. Here, we systematically studied the effects of different processing parameters of inductively coupled plasma reactive ion etching (ICP RIE) on the Ti nanostructures. The resultant Ti surfaces were characterized by using scanning electron microscopy and contact angle measurements. The specimens etched using different chamber pressures were chosen for measurement of the mechanical properties using nanoindentation. The etched surfaces revealed various morphologies, from flat porous structures to relatively rough surfaces consisting of nanopillars with diameters between 26.4 ± 7.0 nm and 76.0 ± 24.4 nm and lengths between 0.5 ± 0.1 μm and 5.2 ± 0.3 μm. The wettability of the surfaces widely varied in the entire range of hydrophilicity. The structures obtained at higher chamber pressure showed enhanced mechanical properties. The bactericidal behavior of selected surfaces was assessed against Staphylococcus aureus and Escherichia coli bacteria while their cytocompatibility was evaluated with murine preosteoblasts. The findings indicated the potential of such ICP RIE Ti structures to incorporate both bactericidal and osteogenic activity, and pointed out that optimization of the process conditions is essential to maximize these biofunctionalities.
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http://dx.doi.org/10.1038/s41598-019-55093-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906493PMC
December 2019

Bactericidal effects of nanopatterns: A systematic review.

Acta Biomater 2019 01 29;83:29-36. Epub 2018 Sep 29.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, 2628CD Delft, The Netherlands.

We systematically reviewed the currently available evidence on how the design parameters of surface nanopatterns (e.g. height, diameter, and interspacing) relate to their bactericidal behavior. The systematic search of the literature resulted in 46 studies that satisfied the inclusion criteria of examining the bactericidal behavior of nanopatterns with known design parameters in absence of antibacterial agents. Twelve of the included studies also assessed the cytocompatibility of the nanopatterns. Natural and synthetic nanopatterns with a wide range of design parameters were reported in the included studies to exhibit bactericidal behavior. However, most design parameters were in the following ranges: heights of 100-1000 nm, diameters of 10-300 nm, and interspacings of  <500 nm. The most commonly used type of nanopatterns were nanopillars, which could kill bacteria in the following range of design parameters: heights of 100-900 nm, diameters of 20-207 nm, and interspacings of 9-380 nm. The vast majority of the cytocompatibility studies (11 out of 12) showed no adverse effects of bactericidal nanopatterns with the only exception being nanopatterns with extremely high aspect ratios. The paper concludes with a discussion on the evidence available in the literature regarding the killing mechanisms of nanopatterns and the effects of other parameters including surface affinity of bacteria, cell size, and extracellular polymeric substance (EPS) on the killing efficiency. STATEMENT OF SIGNIFICANCE: The use of nanopatterns to kill bacteria without the need for antibiotics represents a rapidly growing area of research. However, the optimum design parameters to maximize the bactericidal behavior of such physical features need to be fully identified. The present manuscript provides a systematic review of the bactericidal nanopatterned surfaces. Identifying the effective range of dimensions in terms of height, diameter, and interspacings, as well as covering their impact on mammalian cells, has enabled a comprehensive discussion including the bactericidal mechanisms and the factors controlling the bactericidal efficiency. Overall, this review helps the readers have a better understanding of the state-of-the-art in the design of bactericidal nanopatterns, serving as a design guideline and contributing to the design of future experimental studies.
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http://dx.doi.org/10.1016/j.actbio.2018.09.059DOI Listing
January 2019

Amniotic membrane and its epithelial and mesenchymal stem cells as an appropriate source for skin tissue engineering and regenerative medicine.

Artif Cells Nanomed Biotechnol 2018 24;46(sup2):431-440. Epub 2018 Apr 24.

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

One of the main goals of tissue engineering and regenerative medicine is to develop skin substitutes for treating deep dermal and full thickness wounds. In this regard, both scaffold and cell source have a fundamental role to achieve exactly the same histological and physiological analog of skin. Amnion epithelial and mesenchymal cells possess the characteristics of pluripotent stem cells which have the capability to differentiate into all three germ layers and can be obtained without any ethical concern. Amniotic cells also produce different growth factors, angio-modulatory cytokines, anti-bacterial peptides and a wide range of anti-inflammatory agents which eventually cause acceleration in wound healing. In addition, amniotic membrane matrix exhibits characteristics of an ideal scaffold and skin substitute through various types of extracellular proteins such as collagens, laminins and fibronectins which serve as an anchor for cell attachment and proliferation, a bed for cell delivery and a reservoir of drugs and growth factors involved in wound healing process. Recently, isolation of amniotic cells exosomes, surface modification and cross-linking approaches, construction of amnion based nanocomposites and impregnation of amnion with nanoparticles, construction of amnion hydrogel and micronizing process promoted its properties for tissue engineering. In this manuscript, the recent progress was reviewed which approve that amnion-derived cells and matrix have potential to be involved in skin substitutes; an enriched cell containing scaffold which has a great capability to be translated into the clinic.
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http://dx.doi.org/10.1080/21691401.2018.1458730DOI Listing
June 2019

Immunological compatibility status of placenta-derived stem cells is mediated by scaffold 3D structure.

Artif Cells Nanomed Biotechnol 2018 23;46(sup1):876-884. Epub 2018 Feb 23.

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

Placenta-derived amniotic epithelial cells (AECs), a great cell source for tissue engineering and stem cell therapy, are immunologically inert in their native state; however, immunological changes in these cells after culture and differentiation have challenged their applications. The aim of this study was to investigate the effect of 2D and 3D scaffolds on human lymphocyte antigens (HLA) expression by AECs. The effect of different preparation parameters including pre-freezing time and temperature was evaluated on 3D chitosan-gelatine scaffolds properties. Evaluation of MHC class I, HLA-DR and HLA-G expression in AECs after 7 d culture on 2D bed and 3D scaffold of chitosan-gelatine showed that culture of AECs on the 2D substrate up-regulated MHC class I and HLA-DR protein markers on AECs surface and down-regulated HLA-G protein. In contrast, 3D scaffold did not increase protein expression of MHC class I and HLA-DR. Moreover, HLA-G protein expression remained unchanged in 3D culture. These results confirm that 3D scaffold can remain AECs in their native immunological state and modification of physical properties of the scaffold is a key regulator of immunological markers at the gene and protein expression levels; a strategy which circumvents rejection challenge of amniotic stem cells to be translated into the clinic.
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http://dx.doi.org/10.1080/21691401.2018.1438452DOI Listing
August 2019

Induction of antimicrobial peptides secretion by IL-1β enhances human amniotic membrane for regenerative medicine.

Sci Rep 2017 12 5;7(1):17022. Epub 2017 Dec 5.

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

Due to antibacterial characteristic, amnion has been frequently used in different clinical situations. Developing an in vitro method to augment endogenous antibacterial ingredient of amniotic epithelial and mesenchymal stem cells is desirable for a higher efficacy of this promising biomaterial. In this study, epithelial or mesenchymal side dependent effect of amniotic membrane (AM) on antibacterial activity against some laboratory and clinical isolated strains was investigated by modified disk diffusion method and colony count assay. The effect of exposure to IL-1β in production and release of antibacterial ingredients was investigated by ELISA assay. The results showed that there is no significant difference between epithelial and mesenchymal sides of amnion in inhibition of bacterial growth. Although the results of disk diffusion showed that the AM inhibitory effect depends on bacterial genus and strain, colony count assay showed that the extract of AM inhibits all investigated bacterial strains. The exposure of AM to IL-1β leads to a higher level of antibacterial peptides secretion including elafin, HBD-2, HBD-3 and cathelicidic LL-37. Based on these results, amniotic cells possess antibacterial activity which can be augmented by inflammatory signal inducers; a process which make amnion and its epithelial and mesenchymal stem cells more suitable for tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1038/s41598-017-17210-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717175PMC
December 2017

Design and fabrication of GelMA/chitosan nanoparticles composite hydrogel for angiogenic growth factor delivery.

Artif Cells Nanomed Biotechnol 2018 Dec 24;46(8):1799-1808. Epub 2017 Oct 24.

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

The cellular microenvironment plays a crucial role in improving cell response and function of an engineered tissue. Scaffolds mimicking the native ECM and capable of releasing growth factors are great candidates for tissue engineering applications. Gelatin methacryloyl (GelMA) hydrogel, a photocrosslinkable biomaterial possessing tunable properties, has been widely used in tissue engineering. It has been suggested that incorporating micro/nano carriers in GelMA could provide a sustained release of growth factors. Specifically, chitosan nanoparticles can be used for growth factor delivery due to its biocompatibility, easy method of synthesis, and preventing the biomolecule from degradation. In this study, GelMA/chitosan nanoparticles composite hydrogel was developed to deliver an angiogenic growth factor (bFGF). The hydrogel was prepared by photopolymerization and its chemical and physical properties were characterized. Its degradation and swelling characteristics were also evaluated. The size of nanoparticles was evaluated and the profile of bFGF release from the hydrogel and its effect on the viability of fibroblast cells was studied. The results showed that GelMA/chitosan nanoparticles can significantly promote cell proliferation due to its biocompatible structure and providing a sustained profile of bFGF release. This hydrogel scaffold can be used for efficient delivery of bFGF in various applications and especially for angiogenesis.
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http://dx.doi.org/10.1080/21691401.2017.1392970DOI Listing
December 2018

The effect of cryopreservation on anti-cancer activity of human amniotic membrane.

Cryobiology 2017 02 9;74:61-67. Epub 2016 Dec 9.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Human amniotic membrane (AM) is an appropriate candidate for treatment of cancer due to special properties, such as inhibition of angiogenesis and secretion of pro-apoptotic factors. This research was designed to evaluate the impact of cryopreservation on cancer cell death induction and anti-angiogenic properties of the AM. Cancer cells were treated with fresh and cryopreserved amniotic condition medium during 24 h and cancer cell viability was determined by MTT assay. To evaluate angiogenesis, the rat aorta ring assay was performed for both fresh and cryopreserved AM within 7 days. In addition, four anti-angiogenic factors Tissue Inhibitor of Matrix Metalloproteinase-1 and 2 (TIMP-1 and TIMP-2), Thrombospondin, and Endostatin were measured by ELISA assay before and after cryopreservation. The results showed that the viability of cultured cancer cells dose-dependently decreased after treatment with condition medium of fresh and cryopreserved tissue and no significant difference was observed between the fresh and cryopreserved AM. The results revealed that the amniotic epithelial stem cells inhibit the penetration of fibroblast-like cells and angiogenesis. Moreover, the penetration of fibroblast-like cells in both epithelial and mesenchymal sides of fresh and cryopreserved AM was observed after removing of epithelial cells. The cryopreservation procedure significantly decreased anti-angiogenic factors TIMP-1, TIMP-2, Thrombospondin, and Endostatin which shows that angio-modulatory property is not fully dependent on proteomic and metabolomic profiles of the AM. These promising results demonstrate that cancer cell death induction and anti-angiogenic properties of the AM were maintained within cryopreservation; a procedure which can circumvent limitations of the fresh AM.
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http://dx.doi.org/10.1016/j.cryobiol.2016.12.001DOI Listing
February 2017