Chemical Engineering / Kimya Mühendisliği
Permanent URI for this collectionhttps://hdl.handle.net/11147/14
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Review Citation - WoS: 39Citation - Scopus: 37Engineered Liposomes in Interventional Theranostics of Solid Tumors(American Chemical Society, 2023) Kommineni, Nagavendra; Chaudhari, Ruchita; Conde, Joao; Cecen, Berivan; Chandra, Pranjal; Prasad, Rajendra; Tamburacı, SedefEngineered liposomal nanoparticles have unique characteristicsas cargo carriers in cancer care and therapeutics. Liposomal theranosticshave shown significant progress in preclinical and clinical cancermodels in the past few years. Liposomal hybrid systems have not onlybeen approved by the FDA but have also reached the market level. Nanosizedliposomes are clinically proven systems for delivering multiple therapeuticas well as imaging agents to the target sites in (i) cancer theranosticsof solid tumors, (ii) image-guided therapeutics, and (iii) combinationtherapeutic applications. The choice of diagnostics and therapeuticscan intervene in the theranostics property of the engineered system.However, integrating imaging and therapeutics probes within lipidself-assembly liposome may compromise their overalltheranostics performance. On the other hand, liposomal systems sufferfrom their fragile nature, site-selective tumor targeting, specificbiodistribution and premature leakage of loaded cargo molecules beforereaching the target site. Various engineering approaches, viz., grafting,conjugation, encapsulations, etc., have been investigated to overcomethe aforementioned issues. It has been studied that surface-engineeredliposomes demonstrate better tumor selectivity and improved therapeuticactivity and retention in cells/or solid tumors. It should be notedthat several other parameters like reproducibility, stability, smoothcirculation, toxicity of vital organs, patient compliance, etc. mustbe addressed before using liposomal theranostics agents in solid tumorsor clinical models. Herein, we have reviewed the importance and challengesof liposomal medicines in targeted cancer theranostics with theirpreclinical and clinical progress and a translational overview.Article Citation - WoS: 17Citation - Scopus: 16Development of Cissus Quadrangularis-Loaded Poss-Reinforced Chitosan-Based Bilayer Sponges for Wound Healing Applications: Drug Release and in Vitro Bioactivity(American Chemical Society, 2023) Değer Aker, Sibel; Tamburacı, Sedef; Tıhmınlıoğlu, FundaNowadays, antibiotic-loaded biomaterials have been widelyusedin wound healing applications. However, the use of natural extractshas come into prominence as an alternative to these antimicrobialagents in the recent period. Among natural sources, Cissus quadrangularis (CQ) herbal extract is usedfor treatment of bone and skin diseases in ayurvedic medicine dueto its antibacterial and anti-inflammatory effects. In this study,chitosan-based bilayer wound dressings were fabricated with electrospinningand freeze-drying techniques. CQ extract-loaded chitosan nanofiberswere coated on chitosan/POSS nanocomposite sponges using an electrospinningmethod. The bilayer sponge is designed to treat exudate wounds whilemimicking the layered structure of skin tissue. Bilayer wound dressingswere investigated with regard to the morphology and physical and mechanicalproperties. In addition, CQ release from bilayer wound dressings and in vitro bioactivity studies were performed to determinethe effect of POSS nanoparticles and CQ extract loading on NIH/3T3and HS2 cells. The morphology of nanofibers was investigated withSEM analysis. Physical characteristics of bilayer wound dressingswere determined with FT-IR analysis, swelling study, open porositydetermination, and mechanical test. The antimicrobial activity ofCQ extract released from bilayer sponges was investigated with a discdiffusion method. Bilayer wound dressings' in vitro bioactivity was examined using cytotoxicity determination, woundhealing assay, proliferation, and the secretion of biomarkers forskin tissue regeneration. The nanofiber layer diameter was obtainedin the range of 77.9-97.4 nm. The water vapor permeabilityof the bilayer dressing was obtained as 4021 to 4609 g/m(2)day, as it is in the ideal range for wound repair. The release ofthe CQ extract over 4 days reached 78-80% cumulative release.The release media were found to be antibacterial against Gram-negativeand Gram-positive bacteria. In vitro studies showedthat both CQ extract and POSS incorporation induced cell proliferationas well as wound healing activity and collagen deposition. As a result,CQ-loaded bilayer CHI-POSS nanocomposites were found as a potentialcandidate for wound healing applications.Article Citation - WoS: 11Fabrication of Helix Aspersa Extract Loaded Gradient Scaffold With an Integrated Architecture for Osteochondral Tissue Regeneration: Morphology, Structure, and in Vitro Bioactivity [2](American Chemical Society, 2023) Tamburacı, Sedef; Perpelek, Merve; Aydemir, Selma; Baykara, Başak; Havıtçıoğlu, Hasan; Tıhmınlıoğlu, FundaRegeneration of osteochondral tissue with its layered complex structure and limited self-repair capacity has come into prominence as an application area for biomaterial design. Thus, literature studies have aimed to design multilayered scaffolds using natural polymers to mimic its unique structure. In this study, fabricated scaffolds are composed of transition layers both chemically and morphologically to mimic the gradient structure of osteochondral tissue. The aim of this study is to produce gradient chitosan (CHI) scaffolds with bioactive snail (Helix aspersa) mucus (M) and slime (S) extract and investigate the structures regarding their physicochemical, mechanical, and morphological characteristics as well as in vitro cytocompatibility and bioactivity. Gradient scaffolds (CHI-M and CHI-S) were fabricated via a layer-by-layer freezing and lyophilization technique. Highly porous and continuous 3D structures were obtained and observed with SEM analysis. In addition, scaffolds were physically characterized with water uptake test, micro-CT, mechanical analysis (compression tests), and XRD analysis. In vitro bioactivity of scaffolds was investigated by co-culturing Saos-2 and SW1353 cells on each compartment of gradient scaffolds. Osteogenic activity of Saos-2 cells on extract loaded gradient scaffolds was investigated in terms of ALP secretion, osteocalcin (OC) production, and biomineralization. Chondrogenic bioactivity of SW1353 cells was investigated regarding COMP and GAG production and observed with Alcian Blue staining. Both mucus and slime incorporation in the chitosan matrix increased the osteogenic differentiation of Saos-2 and SW1353 cells in comparison to the pristine matrix. In addition, histological and immunohistological staining was performed to investigate ECM formation on gradient scaffolds. Both characterization and in vitro bioactivity results indicated that CHI-M and CHI-S scaffolds show potential for osteochondral tissue regeneration, mimicking the structure as well as enhancing physical characteristics and bioactivity. © 2023 The Authors. Published by American Chemical Society.Article Citation - WoS: 22Citation - Scopus: 23Bioactive Snail Mucus-Slime Extract Loaded Chitosan Scaffolds for Hard Tissue Regeneration: the Effect of Mucoadhesive and Antibacterial Extracts on Physical Characteristics and Bioactivity of Chitosan Matrix(IOP Publishing, 2021) Perpelek, Merve; Tamburacı, Sedef; Aydemir, Selma; Tıhmınlıoğlu, Funda; Baykara, Başak; Karakaşlı, Ahmet; Havıtçıoğlu, HasanBiobased extracts comprise various bioactive components and they are widely used in tissue engineering applications to increase bioactivity as well as physical characteristics of biomaterials. Among animal sources, garden snail Helix aspersa has come into prominence with its antibacterial and regenerative extracts and show potential in tissue regeneration. Thus, in this study, bioactive H. aspersa extracts (slime, mucus) were loaded in chitosan (CHI) matrix to fabricate porous scaffolds for hard tissue regeneration. Physical, chemical properties, antimicrobial activity was determined as well as in vitro bioactivity for bone and cartilage regeneration. Mucus and slime incorporation enhanced mechanical properties and biodegradation rate of CHI matrix. Scanning electron microscopy images showed that the average pore size of the scaffolds decreased with higher extract content. Mucus and slime extracts showed antimicrobial effect on two bacterial strains. In vitro cytotoxicity, osteogenic and chondrogenic activity of the scaffolds were evaluated with Saos-2 and SW1353 cell lines in terms of Alkaline phosphatase activity, biomineralization, GAG, COMP and hydroxyproline content. Cell viability results showed that extracts had a proliferative effect on Saos-2 and SW1353 cells when compared to the control group. Mucus and slime extract loading increased osteogenic and chondrogenic activity. Thus, the bioactive extract loaded CHI scaffolds showed potential for bone and cartilage regeneration with enhanced physical properties and in vitro bioactivity.Article Citation - WoS: 52Citation - Scopus: 54Development of Si Doped Nano Hydroxyapatite Reinforced Bilayer Chitosan Nanocomposite Barrier Membranes for Guided Bone Regeneration(Elsevier, 2021) Tamburacı, Sedef; Tıhmınlıoğlu, FundaGuided Bone Regeneration (GBR) is a widely used process for the treatment of periodontal defects to prevent the formation of surrounding soft tissue at the periodontal defect and to provide hard tissue regeneration. Recently GBR designs have focused on the development of resorbable natural polymer-based barrier membranes due to their biodegradability and excellent biocompatibility. The aim of this study is to fabricate a novel bilayer nanocomposite membrane with microporous sublayer composed of chitosan and Si doped nanohydroxyapatite particles (Si-nHap) and chitosan/PEO nanofiber upper layer. Bilayer membrane was designed to prevent epithelial and fibroblastic cell migration and growth impeding bone formation with its upper layer and to support osteogenic cell bioactivity at the defect site with its sublayer. Microporous and nanofiber layers were fabricated by using freeze-drying and electrospinning techniques respectively. The effect of Si-nHap content on the morphological, mechanical and physical properties of the composites were investigated using SEM, AFM, micro-Ct, compression test, water uptake capacity and enzymatic degradation study. Antimicrobial properties of nanocomposite membranes were investigated with tube dilution and disk diffusion methods. In vitro cytotoxicity of bilayer membranes was evaluated. Saos-2 and NIH/3T3 proliferation studies were carried out on each layer. In vitro bioactivity of Saos-2 and NIH/3T3 cells were evaluated with ALP activity and hydroxyproline content respectively. Results showed that Si-nHap incorporation enhanced the mechanical and physical properties as well as controlling biodegradability of the polymer matrix. Besides, Si-nHap loading induced the bioactivity of Saos-2 cells by enhancing cell attachment, spreading and biomineralization on the material surface. Thus, results supported that designed bilayer nanocomposite membranes can be used as a potential biomaterial for guided bone regeneration in periodontal applications.Article Citation - WoS: 22Citation - Scopus: 23Multi-Organs for Testing Small-Molecule Drugs: Challenges and Perspectives(MDPI, 2021) Çeçen, Berivan; Karavasili, Christina; Nazir, Mubashir; Bhusal, Anant; Doğan, Elvan; Shahriyari, Fatemeh; Tamburacı, Sedef; Miri, Amir K.Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug–body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Article Citation - WoS: 54Citation - Scopus: 64Bioactive Fish Scale Incorporated Chitosan Biocomposite Scaffolds for Bone Tissue Engineering(Elsevier Ltd., 2019) Kara, Aylin; Tamburacı, Sedef; Tıhmınlıoğlu, Funda; Havıtçıoğlu, HasanRecently, biologically active natural macromolecules have come into prominence to be used as potential materials in scaffold design due to their unique characteristics which can mimic the human tissue structure with their physical and chemical similarity. Among them, fish scale (FS) is a biologically active material with its structural similarity to bone tissue due to including type I collagen and hydroxyapatite and also have distinctive collagen arrangement. In the present study, it is aimed to design a novel composite scaffold with FS incorporation into chitosan (CH) matrix for bone tissue regeneration. Therefore, two biological macromolecules, fish scale and chitosan, were combined to produce bio-composite scaffold. First, FS were decellularized with the chemical method and disrupted physically as microparticles (100 in), followed by dispersal in CH with ultrasonic homogenisation, CH/FS scaffolds were fabricated by lyophilization technique. Scaffolds were characterized physically, chemically, mechanically, and morphologically. SEM and porosity results showed that CH/FS scaffolds have uniform pore structure showing high porosity. Mechanical properties and degradation rate are enhanced with increasing FS content. In vitro cytotoxicity, proliferation and osteogenic activity of the scaffolds were evaluated with SaOS-2 cell line. CH/FS scaffolds did not show any cytotoxicity effect and the cells were gradually proliferated during culture period. Cell viability results showed that, FS microparticles had a proliferative effect on SaOS-2 cells when compared to control group. ALP activity and biomineralization studies indicated that FS micro particle reinforcement increased osteogenic activity during culture period. As a biological macromolecule with unique characteristics, FS was found as cytocompatible and provided promising effects as reinforcement agents for polymeric scaffolds. In conclusion, fabricated CH/FS bio-composites showed potential for bone tissue engineering applications. (C) 2019 Elsevier B.V. All rights reserved.Article Citation - WoS: 43Citation - Scopus: 47Bioactive Diatomite and Poss Silica Cage Reinforced Chitosan/Na-carboxymethyl Cellulose Polyelectrolyte Scaffolds for Hard Tissue Regeneration(Elsevier, 2019) Tamburacı, Sedef; Kimna, Ceren; Tıhmınlıoğlu, FundaRecently, natural polymers are reinforced with silica particles for hard tissue engineering applications to induce bone regeneration. In this study, as two novel bioactive agents, effects of diatomite and polyhedral oligomeric silsesquioxanes (POSS) on chitosan (CS)/Na-carboxymethylcellulose (Na-CMC) polymer blend scaffolds are examined. In addition, the effect of silica reinforcements was compared with Si-substituted nano-hydroxyapatite (Si-Hap) particles. The morphology, physical and chemical structures of the scaffolds were characterized with SEM, liquid displacement, FT-IR, mechanical analysis, swelling and degradation studies. The particle size and the crystal structure of diatomite, POSS and Si-Hap particles were determined with DLS and XRD analyses. In vitro studies were performed to figure out the cytotoxicity, proliferation, ALP activity, osteocalcin production and biomineralization to demonstrate the promising use of natural silica particles in bone regeneration. Freeze-dried scaffolds showed 190-307 mu m pore size range and 61-70% porosity. Both inorganic reinforcements increased the mechanical strength, enhanced the water uptake capacity and fastened the degradation rate. The nanocomposite scaffolds did not show any cytotoxic effect and enhanced the surface mineralization in osteogenic medium. Thus, diatomite and POSS cage structures can be potential reinforcements for nanocomposite design in hard tissue engineering applications.Article Citation - WoS: 69Citation - Scopus: 77Novel Zein-Based Multilayer Wound Dressing Membranes With Controlled Release of Gentamicin(John Wiley and Sons Inc., 2019) Kimna, Ceren; Tamburacı, Sedef; Tıhmınlıoğlu, FundaRecently, functional multilayer scaffolds with controlled drug release ability come into prominence for wound healing applications to mimic the layered structure of skin tissue and prevent the possible infections at the defect site. In this study, controlled antibiotic releasing zein bilayer membranes were fabricated for treatment of acute skin infections. Gentamicin loaded fibers were prepared by electrospinning on the membrane surface. Membranes were characterized with scanning electron microscope, atomic force microscopy, Fourier transform infrared spectroscopy, contact angle, mechanical analysis, swelling, degradation, and water vapor permeability studies. In vitro cytotoxicity, cell attachment, and proliferation were investigated. Cell attachment on fiber layer was observed with fluorescence imaging. Fabricated fibers showed structural similarity to the skin tissue layers with a fiber diameter range of 350-425 nm and film thickness in the range of 311-361 mu m. Mechanical properties were found compatible with the skin tissue. In addition, membranes showed antimicrobial activity against Staphylococcus aureus and Escherichia coli. The sustained release was achieved with a cumulative release of 94%. Membranes did not show any cytotoxic effect. NIH/3T3 and HS2 cell lines were proliferated on each layer mimicking the multilayer skin tissue. Hence, zein-based bilayer membrane showed promising properties to be used as a potential antimicrobial wound dressing for skin tissue regeneration. (c) 2018 Wiley Periodicals, Inc.Article Citation - WoS: 26Citation - Scopus: 28Osteoconductive 3d Porous Composite Scaffold From Regenerated Cellulose and Cuttlebone-Derived Hydroxyapatite(SAGE Publications Inc., 2019) Palaveniene, Alisa; Tamburacı, Sedef; Kimna, Ceren; Glambaite, Kristina; Baniukaitiene, Odeta; Tıhmınlıoğlu, Funda; Liesiene, JolantaRecently, usage of marine-derived materials in biomedical field has come into prominence due to their promising characteristics such as biocompatibility, low immunogenicity and wide accessibility. Among these marine sources, cuttlebone has been used as a valuable component with its trace elemental composition in traditional medicine. Recent studies have focused on the use of cuttlebone as a bioactive agent for tissue engineering applications. In this study, hydroxyapatite particles were obtained by hydrothermal synthesis of cuttlebone and incorporated to cellulose scaffolds to fabricate an osteoconductive composite scaffold for bone regeneration. Elemental analysis of raw cuttlebone material from different coastal zones and cuttlebone-derived HAp showed that various macro-, micro- and trace elements - Ca, P, Na, Mg, Cu, Sr, Cl, K, S, Br, Fe and Zn were found in a very similar amount. Moreover, biologically unfavorable heavy metals, such as Ag, Cd, Pb or V, were not detected in any cuttlebone specimen. Carbonated hydroxyapatite particle was further synthesized from cuttlebone microparticles via hydrothermal treatment and used as a mineral filler for the preparation of cellulose-based composite scaffolds. Interconnected highly porous structure of the scaffolds was confirmed by micro-computed tomography. The mean pore size of the scaffolds was 510 mu m with a porosity of 85%. The scaffolds were mechanically characterized with a compression test and cuttlebone-derived HAp incorporation enhanced the mechanical properties of cellulose scaffolds. In vitro cell culture studies indicated that MG-63 cells proliferated well on scaffolds. In addition, cuttlebone-derived hydroxyapatite significantly induced the ALP activity and osteocalcin secretion. Besides, HAp incorporation increased the surface mineralization which is the major step for bone tissue regeneration.