Aldemir Dikici, Betül
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Dikici, B. Aldemir
Dikici, Betul Aldemir
Aldemir, Betül
Dikici, Betül Aldemir
Aldemir, Betul
Aldemir Dikici, B.
Aldemir Dikici, Betul
Dikici, Betul Aldemir
Aldemir, Betül
Dikici, Betül Aldemir
Aldemir, Betul
Aldemir Dikici, B.
Aldemir Dikici, Betul
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betulaldemir@iyte.edu.tr
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03.01. Department of Bioengineering
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201
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13.40
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| Journal | Count |
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| Polymer | 2 |
| ACS Omega | 1 |
| Biomacromolecules | 1 |
| Biomaterials Advances | 1 |
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Article Impact of Internal Phase Volume on the Physical, Morphological and Mechanical Characteristics of Emulsion Templated Scaffolds(2024) Dikici, Betül AldemirObjectives: The high porosity of tissue engineering scaffolds is advantageous as they provide a high degree of infiltration of nutrients, enable cell penetration, and support vascularisation. However, the mechanical strength is also critical for providing structural support to the defect site throughout the regeneration process. In this study, we aimed to establish a relationship between internal phase volume and emulsion-templated scaffolds' physical, morphological and mechanical characteristics. Methods: In this work, tetra methacrylate functionalised polycaprolactone (4PCLMA) polymers were synthesised via ring-opening polymerisation followed by methacrylation. 4PCLMA-based emulsion templated matrices with 60%, 75% and 82% internal phase volumes were fabricated (P60, P75, and P82). These scaffolds' densities, porosities, average pore and window sizes, degree of interconnectivity values, and mechanical properties were investigated. Results: Increasing internal phase volume reduced the density of the foams by almost two-fold. No direct correlation was observed between average pore size and internal phase volume. Both the average window sizes and the degree of interconnectivity values increase with increasing internal phase volume. Compression modulus values are calculated as 0.46±0.04 MPa, 0.23±0.02 MPa and 0.14±0.01 MPa for P60, P75, and P82, respectively. Increasing internal phase volume from 60% to 82% caused a more than 2-fold reduction in the stiffness of the emulsion-templated matrices. Conclusions: Accordingly, by reporting on this experimental framework, we established a relationship between internal phase volume and the physical, morphological and mechanical characteristics of 4PCMA-based scaffolds to precisely engineer these characteristics for specific tissue engineering applications.Article Citation - WoS: 11Citation - Scopus: 11Quantitative Evaluation of the Pore and Window Sizes of Tissue Engineering Scaffolds on Scanning Electron Microscope Images Using Deep Learning(Amer Chemical Soc, 2024) Karaca, Ilayda; Dikici, Betul AldemirThe morphological characteristics of tissue engineering scaffolds, such as pore and window diameters, are crucial, as they directly impact cell-material interactions, attachment, spreading, infiltration of the cells, degradation rate and the mechanical properties of the scaffolds. Scanning electron microscopy (SEM) is one of the most commonly used techniques for characterizing the microarchitecture of tissue engineering scaffolds due to its advantages, such as being easily accessible and having a short examination time. However, SEM images provide qualitative data that need to be manually measured using software such as ImageJ to quantify the morphological features of the scaffolds. As it is not practical to measure each pore/window in the SEM images as it requires extensive time and effort, only the number of pores/windows is measured and assumed to represent the whole sample, which may cause user bias. Additionally, depending on the number of samples and groups, a study may require measuring thousands of samples and the human error rate may increase. To overcome such problems, in this study, a deep learning model (Pore D2) was developed to quantify the morphological features (such as the pore size and window size) of the open-porous scaffolds automatically for the first time. The developed algorithm was tested on emulsion-templated scaffolds fabricated under different fabrication conditions, such as changing mixing speed, temperature, and surfactant concentration, which resulted in scaffolds with various morphologies. Along with the developed model, blind manual measurements were taken, and the results showed that the developed tool is capable of quantifying pore and window sizes with a high accuracy. Quantifying the morphological features of scaffolds fabricated under different circumstances and controlling these features enable us to engineer tissue engineering scaffolds precisely for specific applications. Pore D2, an open-source software, is available for everyone at the following link: https://github.com/ilaydakaraca/PoreD2.Article Citation - WoS: 27Citation - Scopus: 27In Vivo Bone Regeneration Capacity of Multiscale Porous Polycaprolactone-Based High Internal Phase Emulsion (polyhipe) Scaffolds in a Rat Calvarial Defect Model(American Chemical Society, 2023) Aldemir Dikici, Betül; Chen, Min-Chia; Dikici, Serkan; Chiu, Hsien-Chung; Claeyssens, FrederikGlobally, one of the most common tissue transplantationproceduresis bone grafting. Lately, we have reported the development of polymerizedhigh internal phase emulsions (PolyHIPEs) made of photocurable polycaprolactone(4PCLMA) and shown their potential to be used as bone tissue engineeringscaffolds in vitro. However, it is essential to evaluatethe in vivo performance of these scaffolds to investigatetheir potential in a clinically more relevant manner. Therefore, inthis study, we aimed to compare in vivo performancesof macroporous (fabricated using stereolithography), microporous (fabricatedusing emulsion templating), and multiscale porous (fabricated usingemulsion templating and perforation) scaffolds made of 4PCLMA. Also,3D-printed macroporous scaffolds (fabricated using fused depositionmodeling) made of thermoplastic polycaprolactone were used as a control.Scaffolds were implanted into a critical-sized calvarial defect, animalswere sacrificed 4 or 8 weeks after implantation, and the new boneformation was assessed by micro-computed tomography, dental radiography,and histology. Multiscale porous scaffolds that include both micro-and macropores resulted in higher bone regeneration in the defectarea compared to only macroporous or only microporous scaffolds. Whenone-grade porous scaffolds were compared, microporous scaffolds showedbetter performance than macroporous scaffolds in terms of mineralizedbone volume and tissue regeneration. Micro-CT results revealed thatwhile bone volume/tissue volume (Bv/Tv) values were 8 and 17% at weeks4 and 8 for macroporous scaffolds, they were significantly higherfor microporous scaffolds, with values of 26 and 33%, respectively.Taken together, the results reported in this study showed the potentialapplication of multiscale PolyHIPE scaffolds, in particular, as apromising material for bone regeneration.Article Citation - WoS: 22Citation - Scopus: 21Preparation of Interconnected Pickering Polymerized High Internal Phase Emulsions by Arrested Coalescence(American Chemical Society, 2022) Sherborne, Colin; Reilly, Gwendolen C.; Claeyssens, Frederik; Durgut, Enes; Aldemir Dikici, BetülEmulsion templating is a method that enables the production of highly porous and interconnected polymer foams called polymerized high internal phase emulsions (PolyHIPEs). Since emulsions are inherently unstable systems, they can be stabilized either by surfactants or by particles (Pickering HIPEs). Surfactant-stabilized HIPEs form materials with an interconnected porous structure, while Pickering HIPEs typically form closed pore materials. In this study, we describe a system that uses submicrometer polymer particles to stabilize the emulsions. Polymers fabricated from these Pickering emulsions exhibit, unlike traditional Pickering emulsions, highly interconnected large pore structures, and we related these structures to arrested coalescence. We describe in detail the morphological properties of this system and their dependence on different production parameters. This production method might provide an interesting alternative to poly-surfactant-stabilized-HIPEs, in particular where the application necessitates large pore structures.Article Citation - WoS: 34Citation - Scopus: 34Decellularised Extracellular Matrix Decorated Pcl Polyhipe Scaffolds for Enhanced Cellular Activity, Integration and Angiogenesis(Royal Society of Chemistry, 2021) Dikici, Serkan; Aldemir Dikici, Betül; MacNeil, Sheila; Claeyssens, FrederikWound healing involves a complex series of events where cell-cell and cell-extracellular matrix (ECM) interactions play a key role. Wounding can be simple, such as the loss of the epithelial integrity, or deeper and more complex, reaching to subcutaneous tissues, including blood vessels, muscles and nerves. Rapid neovascularisation of the wounded area is crucial for wound healing as it has a key role in supplying oxygen and nutrients during the highly demanding proliferative phase and transmigration of inflammatory cells to the wound area. One approach to circumvent delayed neovascularisation is the exogenous use of pro-angiogenic factors, which is expensive, highly dose-dependent, and the delivery of them requires a very well-controlled system to avoid leaky, highly permeable and haemorrhagic blood vessel formation. In this study, we decorated polycaprolactone (PCL)-based polymerised high internal phase emulsion (PolyHIPE) scaffolds with fibroblast-derived ECM to assess fibroblast, endothelial cell and keratinocyte activity in vitro and angiogenesis in ex ovo chick chorioallantoic membrane (CAM) assays. Our results showed that the inclusion of ECM in the scaffolds increased the metabolic activity of three types of cells that play a key role in wound healing and stimulated angiogenesis in ex ovo CAM assays over 7 days. Herein, we demonstrated that fibroblast-ECM functionalised PCL PolyHIPE scaffolds appear to have great potential to be used as an active wound dressing to promote angiogenesis and wound healing.Master Thesis Development and Characterization of Surface-Modified Emulsion Templated Scaffolds for Tissue Engineering Applications(01. Izmir Institute of Technology, 2024) Kocagöz, Mehmet; Dikici, Betül Aldemir; Zareıe, Esma Volga BulmuşEmülsiyon şablonlama, yüksek ve açık gözeneklilik sağlayan avantajlı bir iskele üretim yöntemidir. Bu yöntemde hidrofobik polimerlerin su ile karıştırılmasıyla yağ içerisinde su (w/o) emülsiyonları elde edilir. İç faz hacmi %74'ün üzerinde olan polimerize emülsiyonlar, yüksek iç fazlı emülsiyonlar (PolyHIPE'ler) olarak adlandırılır. Polikaprolakton, doku mühendisliğinde yaygın olarak kullanılan sentetik, biyolojik olarak bozunabilen ve biyouyumlu bir polimerdir, ancak malzemenin hidrofobik karakteri hücre-materyal etkileşimlerini sınırlamaktadır. Bu nedenle, bu çalışma kapsamında, emülsiyon şablonlama yöntemi ile üretilmiş, polikaprolakton tetrametakrilat (4PCLMA) esaslı iskelelerin biyolojik performanslarını artırmak için iskelelerin alkali muamelesi ve elde edilen iskelelerin karakterize edilmesi amaçlanmıştır. İlk olarak halka açma polimerizasyonu ile 4PCLMA pre-polimeri sentezlenmiş ve metakrilat grupları ile fonksiyon kazandırılmıştır. 4PCLMA ~%97 metakrilasyon derecesi ile başarıyla sentezlenmiş, 4PCLMA esaslı PolyHIPE'ler emülsiyon şablonlama yöntemi ile üretilmiş, üç farklı konsantrasyonda ve inkübasyon süresinde sodyum hidroksit (NaOH) ile muamele edilmiştir. NaOH işleminin iskelelerin morfolojileri, kütle kaybı, su tutma kapasitesi, mekanik özellikleri, yüzey alanı, hidrofilisitesi ve biyolojik performansı üzerindeki etkileri araştırılmıştır. NaOH uygulamasının iskelelerin ağırlığını ve mekanik mukavemetini azalttığı ancak aynı zamanda iskelelerin su tutma kapasitesini, hidrofilisitesini, yüzey alanını ve protein adsorpsiyon kapasitesini artırdığı görülmüştür. NaOH işleminden sonra PolyHIPE'lerdeki kimyasal değişiklikler spektroskopi ile doğrulanmıştır. In vitro sonuçlar, NaOH uygulamasının L929 hücreleri üzerinde sitotoksisiteye neden olmadığını ve Saos-2 hücrelerinin tutunma ve çoğalma davranışını olumlu yönde etkilediğini göstermiştir. Bu çalışma sonucunda NaOH muamelesinin, emülsiyon şablonlama ile üretilmiş doku iskelelerinin hidrofilisitesini ve biyolojik performansını artırmak adına alternatif bir yüzey modifikasyon yöntemi olarak kullanılabileceği gösterilmiştir.Article Citation - WoS: 18Citation - Scopus: 17Modifying Pickering Polymerized High Internal Phase Emulsion Morphology by Adjusting Particle Hydrophilicity(Elsevier, 2024) Durgut, Enes; Zhou, Muchu; Dikici, Betuel Aldemir; Foudazi, Reza; Claeyssens, FrederikThis study investigates the use of submicron polymeric particles with varying crosslinking densities as the sole stabilizer for producing Polymerized High Internal Phase Emulsions (PolyHIPE). We establish a direct correlation between the crosslinking density and the hydrophilicity of the polymer particles. The hydrophilicity of these particles significantly influences the morphology and rheology of HIPEs. These differences manifest as various morphological variations in the resulting PolyHIPE templates. It was discovered that by increasing the crosslinker weight percentage in the particles from 0 % to 100 %, PolyHIPEs with semi-open, open, and closed porous structures can be obtained. Furthermore, non-crosslinked particles were observed to dissolve in the continuous phase, acting as macromolecular surfactants that generate small pores akin to surfactant-stabilized structures in PolyHIPE. These findings offer fresh insights into the relationship between particle localization at the interface, HIPE rheology, and the formation of pore throats in Pickering PolyHIPEs, leading to the creation of either closed or open porous networks. Additionally, interfacial rheological results demonstrate that particles synthesized with varying monomer-to-crosslinker ratios exhibit different interfacial elasticities, which are linked to PolyHIPE morphology.Article Citation - WoS: 46Citation - Scopus: 46Thiolene- and Polycaprolactone Methacrylate-Based Polymerized High Internal Phase Emulsion (polyhipe) Scaffolds for Tissue Engineering(American Chemical Society, 2022) Aldemir Dikici, Betül; Malayeri, Atra; Sherborne, Colin; Dikici, Serkan; Paterson, Thomas; Dew, Lindsey; Claeyssens, FrederikHighly porous emulsion templated polymers (PolyHIPEs) provide a number of potential advantages in the fabrication of scaffolds for tissue engineering and regenerative medicine. Porosity enables cell ingrowth and nutrient diffusion within, as well as waste removal from, the scaffold. The properties offered by emulsion templating alone include the provision of high interconnected porosity, and, in combination with additive manufacturing, the opportunity to introduce controlled multiscale porosity to complex or custom structures. However, the majority of monomer systems reported for PolyHIPE preparation are unsuitable for clinical applications as they are nondegradable. Thiol-ene chemistry is a promising route to produce biodegradable photocurable PolyHIPEs for the fabrication of scaffolds using conventional or additive manufacturing methods; however, relatively little research has been reported on this approach. This study reports the groundwork to fabricate thiol- and polycaprolactone (PCL)-based PolyHIPE materials via a photoinitiated thiolene click reaction. Two different formulations, either three-arm PCL methacrylate (3PCLMA) or four-arm PCL methacrylate (4PCLMA) moieties, were used in the PolyHIPE formulation. Biocompatibility of the PolyHIPEs was investigated using human dermal fibroblasts (HDFs) and human osteosarcoma cell line (MG-63) by DNA quantification assay, and developed PolyHIPEs were shown to be capable of supporting cell attachment and viability.Article Citation - WoS: 4Citation - Scopus: 4Surface Modification Via Alkali Treatment and Its Effect on the Physicochemical and Biological Properties of Emulsion Templated Scaffolds(Elsevier Sci Ltd, 2025) Kocagoz, Mehmet; Tihminlioglu, Funda; Dikici, Betul AldemirEmulsion templating is an advantageous scaffold fabrication technique that provides high interconnectivity, high porosity, and control of the scaffold architecture. Polymerised emulsions with an internal phase ratio greater than 74 % are named Polymerised High Internal Phase Emulsions (PolyHIPEs). Polycaprolactone (PCL) is a synthetic, biodegradable, and biocompatible polymer widely used in tissue engineering, but the material-cell interaction of PCL-based biomaterials has been found to be limited due to the material's high hydrophobicity. This study aims to develop emulsion-templated polycaprolactone tetramethacrylate (4PCLMA)-based scaffolds and improve their biological performance using an alkaline surface modification method. For this purpose, 4PCLMA was successfully synthesised, and highly porous scaffolds were developed. PolyHIPEs were incubated in three different sodium hydroxide (NaOH) concentrations for three different incubation times. Chemical, morphological, mechanical characterisation, mass loss, water absorption capacity, water contact angle, Brunauer-Emmett-Teller analyses and biological investigations were conducted on NaOH-treated scaffolds in comparison with the control. The chemical changes induced by NaOH treatment in PolyHIPEs were confirmed by Fourier-transform infrared spectroscopy. NaOH treatment increased the water absorption capacity, hydrophilicity, surface area, and protein adsorption but decreased the weight and mechanical strength of the scaffolds. In vitro results showed that NaOH treatment did not cause cytotoxicity in L929 cells and positively affected the cell adhesion and proliferation behaviour of Saos-2 cells. This study suggests surface modification of biodegradable synthetic polymer-based PolyHIPEs by NaOH treatment as a simple, scalable and cost-effective approach to enhance cell-material interactions of the material without causing a significant change in the overall morphology, contributing to the advancement of next-generation healthcare technologies.Review Citation - WoS: 17Citation - Scopus: 16Engineering Periodontal Tissue Interfaces Using Multiphasic Scaffolds and Membranes for Guided Bone and Tissue Regeneration(Elsevier, 2024) Özkendir, Özge; Karaca, İlayda; Çullu, Selin; Yaşar, Hüsniye Nur,; Erdoğan, Oğulcan; Dikici, Serkan; Dikici, Betul AldemirPeriodontal diseases are one of the greatest healthcare burdens worldwide. The periodontal tissue compartment is an anatomical tissue interface formed from the periodontal ligament, gingiva, cementum, and bone. This multifaceted composition makes tissue engineering strategies challenging to develop due to the interface of hard and soft tissues requiring multiphase scaffolds to recreate the native tissue architecture. Multilayer constructs can better mimic tissue interfaces due to the individually tuneable layers. They have different characteristics in each layer, with modulation of mechanical properties, material type, porosity, pore size, morphology, degradation properties, and drug-releasing profile all possible. The greatest challenge of multilayer constructs is to mechanically integrate consecutive layers to avoid delamination, especially when using multiple manufacturing processes. Here, we review the development of multilayer scaffolds that aim to recapitulate native periodontal tissue interfaces in terms of physical, chemical, and biological characteristics. Important properties of multiphasic biodegradable scaffolds are highlighted and summarised, with design requirements, biomaterials, and fabrication methods, as well as post-treatment and drug/growth factor incorporation discussed.