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Osteokondral doku hasarı, hastalıktan travmaya kadar farklı nedenlerle ortaya çıkabilen ciddi bir sağlık sorunudur. Osteokondral arayüz defektleri yaygın olarak hem kıkırdak (hiyalin) hem de destekleyici subkondral kemiğin lezyonlarını içermektedir. Hasarın ortopedik cerrahi ile fonksiyonel onarımı, osteokondral yapının karmaşıklığı göz önüne alındığında oldukça zordur. Osteokondral doku mühendisliği, kemik, kıkırdak ve kemik-kıkırdak arayüzünün onarımı ve yenilenmesi için; yapısal iskelelerin, biyoaktif moleküllerin ve hücrelerin kullanımı ile bu zorlukların üstesinden gelmeyi amaçlamaktadır. Gözenekli iskeleler, lifler ve hidrojeller gibi çeşitli matris yapıları, aynı anda kıkırdak, orta kalsifiye kıkırdak ve kemik dokularını restore etmek için tasarlanmaktadır (Yang ve ark., 2017; Ai ve ark., 2021; Wei ve ark., 2021).Bu çalışmada, 3B-biyoyazıcı tekniği ile kök hücre yüklü, TGF-ß1 ve rhBMP-2 salımı yapabilen çift-tabakalı nanohibrit hidrojel temelli doku iskeleleri geliştirilmiştir. Doku iskeleleri 3B-biyobaskı yöntemi ile jelatin metakrilat (GelMA), kitosan metakrilat (KitMA) ve hidrotermal metot ile üretilen LDH nanopartiküllerinin (çift katmanlı hidroksit bileşikleri) Irgacure2959 fotobaşlatıcı varlığında yazdırılması ve sonrasında UV ışık altında kürlenmesi ile hazırlanmıştır. LDH nanopartiküllerine yüklenen TGF-ß1 ve rhBMP-2 sinyal molekülerinin nanopartiküllerden ve doku iskelelerinden in vitro salım davranışları enzim-bağlı immünosorbent testi (ELISA) ile incelenmiştir. Fiziksel, kimyasal ve mekaniksel özellikleri karakterize edilen doku iskelelerine enkapsüle edilen kök hücrelerin canlılığı (canlı/ölü testi), morfolojisi (DAPI/Aktin boyama), gelişimi, proliferasyonu (PrestoBlue analizi), osteojenik ve kondrojenik farklılaşma özellikleri (immünfloresan boyamalar ve PCR analizleri) incelenmiştir. Doku iskelelerinin kemik ve kıkırdak onarımına etkisi sıçanlar üzerinde in vivo osteokondral hasar modelinde değerlendirilmiştir. Tüm sonuçlar birlikte değerlendirildiğinde, geliştirilen nanohibrit çift-tabakalı platformun osteojenik/kondrojenik farklılaşmayı desteklediği ve osteokondral rejenerasyonu teşvik ettiği sonucuna varılmıştır

Wound care is a hot topic in recent years. Recent wound treatment regimens use dressings fabricated from natural materials due to their significant advantages compared to traditional or synthetic dressings. Because of their importance, in this chapter, wound dressings are discussed with an emphasis on the use of natural polymers and their function in the healing process. After a brief introduction to wounds and classification of wound dressings, the chapter focuses on (i) the impact of natural materials on wound dressing design such as mechanical properties, texture, wettability, composition, and porosity; (ii) commonly used natural polymers and their combinations with synthetic polymers and other bioactive components; (iii) state-of-the-art fabrication methods of dressings; and finally, (iv) other nature-derived materials as wound dressings such as decellularized skin extracellular matrix and tissue-engineered skin substitutes.

The desired organ in micro-tissue models of organ-on-a-chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural-based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural-based biomaterials and summarize recent reports on their applications in the design and fabrication of micro-tissue models. This article will help bioengineers select the proper biomaterials based on developing new techn WOS:000748803500001 Q2

Wound care is a hot topic in recent years. Recent wound treatment regimens use dressings fabricated from natural materials due to their significant advantages compared to traditional or synthetic dressings. Because of their importance, in this chapter, wound dressings are discussed with an emphasis on the use of natural polymers and their function in the healing process. After a brief introduction to wounds and classification of wound dressings, the chapter focuses on (i) the impact of natural materials on wound dressing design such as mechanical properties, texture, wettability, composition, and porosity; (ii) commonly used natural polymers and their combinations with synthetic polymers and other bioactive components; (iii) state-of-the-art fabrication methods of dressings; and finally, (iv) other nature-derived materials as wound dressings such as decellularized skin extracellular matrix and tissue-engineered skin substitutes. © 2022 Elsevier B.V. 2-s2.0-85134587588

Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To promote muscle repair and regeneration, various strategies for skeletal muscle tissue engineering have been developed in the last decades. However, there is still a high demand for the development of new methods and materials that promote skeletal muscle repair and functional regeneration to bring approaches closer to therapies in the clinic that structurally and functionally repair muscle. The combination of stem cells, biomaterials, and biomolecules is used to induce skeletal muscle regeneration. In this review, we provide an overview of different cell types used to treat skeletal muscle injury, highlight current strategies in biomaterial-based approaches, the importance of topography for the successful creation of functional striated muscle fibers, and discuss novel methods for muscle regeneration and challenges for their future clinical implementation.

Sutures, staples, clips, and skin closure strips are used as the gold standard to close wounds after an injury. In spite of being the present standard of care, the utilization of these conventional methods is precarious amid complicated and sensitive surgeries such as vascular anastomosis, ocular surgeries, nerve repair, or due to the high-risk components included. Tissue adhesives function as an interface to connect the surfaces of wound edges and prevent them from separation. They are fluid or semi-fluid mixtures that can be easily used to seal any wound of any morphology-uniform or irregular. As such, they provide alternatives to new and novel platforms for wound closure methods. In this review, we offer a background on the improvement of distinctive tissue adhesives focusing on the chemistry of some of these products that have been a commercial success from the clinical application perspective. This review is aimed to provide a guide toward the innovation of tissue bioadhesive materials and their associated biomedical applications. WOS:000637808000033 33425002 Q1

Wound repair is a complex process that has not been entirely understood. It can conclude in several irregularities. Hence, designing an appropriate wound dressing that can accelerate the healing period is critical. Infections, a major obstacle to wound repair, cause an elevated inflammatory responses and result in ultimate outcome of incomplete and prolonged wound repair. To overcome these shortcomings, there is a growing requirement for antibacterial wound dressings. Dressings with antibacterial activities and multifunctional behaviors are highly anticipated to avoid the wound infection for successful healing. The aim of this review is not only to concentrate on the importance of antibacterial dressings for wound healing applications but also to discuss recent studies and some future perspectives about antibacterial wound dressings. WOS:000578645500001 2-s2.0-85092403055 PubMed: 33047502

Four-dimensional (4D) bioprinting, is generally accepted as the future ofbiofabrication technologies. 4D bioprinting develops dynamic and 3D basedbiological materials which can shift their shapes or alter their behaviors when severalstimulants like electricity, temperature, humidity, magnetic etc. are applied. In thisreview, we highlighted the important aspects of several smart materials for 4Dbioprinting that have been used recently for biofabrication researches. It is believedthat in immediate future, smart materials and 4D Bioprinting techniques will have anexcessive importance for designing of soft robotic systems and architecture ofhierarchial, compex, thick and vascularized tissue structures, Dört boyutlu (4B) biyobaskı tekniklerinin biyofabrikasyon teknolojilerinin geleceğiolduğu düşünülmektedir. Elektrik, sıcaklık, nem, manyetik vs. gibi uyarıcılar aracılığıile şekil değiştiren akıllı malzemeler kullanılarak ortaya çıkartılmış olan 4B biyobaskıtekniği, 3B biyolojik materyallerden oluşmuş ve zamanla şekil değiştirebilen yapılarüretilebilmektir. Bu mini derlemede bu alanda son yıllarda ortaya konmuş olan pekçok akıllı malzeme ve bunların önemleri açıklanmıştır. Akıllı malzemelerin ve 4Bbiyoyazıcı tekniklerinin çok yakın bir gelecek içerisinde yumuşak robotik sistemlerintasarımlarında ve hiyerarşik, kompleks, kalın ve damar dokusu eklemlenmiş dokuyapılarının tasarımlanmasında aşırı derecede önem kazanacağı düşünülmektedir.

The skin is the largest and most exposed organ in the human body. Not only it is involved in numerous biological processes essential for life but also it represents a significant endpoint for the application of pharmaceuticals. The area of in vitro skin tissue engineering has been progressing extensively in recent years. Advanced in vitro human skin models strongly impact the discovery of new drugs thanks to the enhanced screening efficiency and reliability. Nowadays, animal models are largely employed at the preclinical stage of new pharmaceutical compounds development for both risk assessment evaluation and pharmacokinetic studies. On the other hand, animal models often insufficiently foresee the human reaction due to the variations in skin immunity and physiology. Skin-on-chips devices offer innovative and state-of-the-art platforms essential to overcome these limitations. In the present review, we focus on the contribution of skin-on-chip platforms in fundamental research and applied medical research. In addition, we also highlighted the technical and practical difficulties that must be overcome to enhance skin-on-chip platforms, e. g. embedding electrical measurements, for improved modeling of human diseases as well as of new drug discovery and development. WOS:000468552000002 30727878 Q3

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano- and micro-technologies. In addition, current hydrogel-based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues.

Nanotechnology offers significant potential in regenerative medicine, specifically with the ability to mimic tissue architecture at the nanoscale. In this perspective, we highlight key achievements in the nanotechnology field for successfully mimicking the composition and structure of different tissues, and the development of bio-inspired nanotechnologies and functional nanomaterials to improve tissue regeneration. Numerous nanomaterials fabricated by electrospinning, nanolithography and self-assembly have been successfully applied to regenerate bone, cartilage, muscle, blood vessel, heart and bladder tissue. We also discuss nanotechnology-based regenerative medicine products in the clinic for tissue engineering applications, although so far most of them are focused on bone implants and fillers. We believe that recent advances in nanotechnologies will enable new applications for tissue regeneration in the near future.

In this work, it is aimed to determine pharmacists' attitude, level of knowledge on extemporaneous formulations including how accurate the formulations are prepared, the problems pharmacists face during preparation, and their approach to solve problems on extemporaneous preparation. Additionally with this work, we aim to gather data on frequently written extemporaneous prescriptions during the recent years. In this work, a questionnaire with the title of Evaluation of pharmacy manager's knowledge and attitude on extemporaneous preparation was applied to pharmacy managers. This questionnaire was completed by 54 community pharmacists. According to our results, it was found that extemporaneous preparations were prescribed to all of the pharmacies that the questionnaire applied, however pharmacists were confronted with various problems during preparation of the formulations.

VEGF, endotelyal hücrelerin proliferasyonu, migrasyonu, farklılaşması ve sağkalımını düzenlemesi nedeniyle vasküler gelişim için çok önemli bir rol oynayan polipeptit yapıda bir büyüme faktörüdür. VEGF, dendritler ve ?Schwann? hücre sağkalımı ve proliferasyonu üzerine direkt olumlu etkileri ile periferal sinir sisteminin rejenerasyonunda da önemli bir rol oynamakta, ayrıca rejenerasyonu anjiyogenez üzerinden indirekt olarak da artırmaktadır. Bu çalışmada VEGF yüklü PLGA mikrokürelerinden VEGF'in kontrollü salımının sağlanması ve sıçanlarda sinir greft prefabrikasyonunun gerçekleştirilmesi amaçlanmıştır. In vitro çalışmalar kapsamında VEGF içeren PLGA mikrokürelerinin hazırlanmasının ardından mikrokürelerin boyut ve SEM analizleri yapılmış, in vitro salım özellikleri ELISA ile belirlenmiştir. Formülasyonların sitotoksisitesi ve VEGF'in proliferasyon etkisini değerlendirmek için MTT testi kullanılmıştır. In vitro çalışmalar sonucunda optimum formülasyon belirlendikten sonra in vivo değerlendirme aşamasına geçilmiştir. In vivo çalışmalar kapsamında ise sıçanlarda sinir greft prefabrikasyonu gerçekleştirmek amacıyla, siyatik sinirin trifikasyonunun distalinde tibial ve peroneal sinirlerde epinöral pencere açılarak, üç ayrı deney grubunda çalışılmıştır. VEGF'in ELISA ile kanda kantitatif analizi ve yürüme yolu analizi yapılmıştır. Ven greftlerinin histolojik değerlendirmeleri ışık mikroskobu ve TEM analizi ile gerçekleştirilmiştir. Işık mikroskobunda incelenen kesitlerde juguler ven içerisinde miyelinli sinir fibrillerin sayısı ve ortalama çapları belirlenmiş, TEM analizi ile akson ve miyelin kılıfının yapısı incelenmiştir. Sonuç olarak, VEGF yüklü mikroküreler hazırlanmış ve otolog ven kullanılarak sinir greft prefabrikasyonu gerçekleştirilmiştir. VEGF, a polypeptide growth factor, is a critical organiser of vascular development due to its ability to regulate proliferation, migration, specialization and survival of endothelial cells. VEGF acts a crucial role on peripheral nerve regeneration by direct effects on axonal outgrowth, neurons, dendrites and survival and proliferation of ?Schwann? cells and also increases regeneration by angiogenesis. The aim of this study was to control the release of VEGF from VEGF loaded PLGA microspheres and produce nerve graft prefabrication on rats. In in vitro studies, after the preparation of VEGF loaded PLGA microspheres, the size and SEM study were done and also in vitro release properties were conducted with ELISA. For evaluation of the cytotoxicity of the formulations and proliferation effect of VEGF, MTT test was performed. According to the in vitro studies, optimum formulation was determined and in vivo evaluation stage was conducted. In in vivo studies, epineural window was opened at the distal side of the siatical nerve trification and three separate groups were studied in order to fulfil nerve graft prefabrication. Quantitative analysis of VEGF in blood using ELISA and walking track for rats were done. Histological evaluation of vein grafts were performed with light microscope and TEM analysis. In specimens examined with light microscope, the number and the average diameter of nerve fibers with myelin were determined. The structure of axon and myelin sheath were examined by TEM analysis. In conclusion VEGF loaded microspheres were prepared and nerve graft prefabrication was produced by using autologous vein. 189

ÖZETVasküler Endotelyal Büyüme Faktörü Yüklü Poli(Laktik-Ko-Glikolik Asit) Mikrokürelerinin In Vitro Ve In Vivo DeğerlendirilmesiVEGF, endotelyal hücrelerin proliferasyonu, migrasyonu, farklılaşması ve sağkalımını düzenlemesi nedeniyle vasküler gelişim için çok önemli bir rol oynayan polipeptit yapıda bir büyüme faktörüdür. VEGF, dendritler ve “Schwann” hücre sağkalımı ve proliferasyonu üzerine direkt olumlu etkileri ile periferal sinir sisteminin rejenerasyonunda da önemli bir rol oynamakta, ayrıca rejenerasyonu anjiyogenez üzerinden indirekt olarak da artırmaktadır. Bu çalışmada VEGF yüklü PLGA mikrokürelerinden VEGF’in kontrollü salımının sağlanması ve sıçanlarda sinir greft prefabrikasyonunun gerçekleştirilmesi amaçlanmıştır. In vitro çalışmalar kapsamında VEGF içeren PLGA mikrokürelerinin hazırlanmasının ardından mikrokürelerin boyut ve SEM analizleri yapılmış, in vitro salım özellikleri ELISA ile belirlenmiştir. Formülasyonların sitotoksisitesi ve VEGF’in proliferasyon etkisini değerlendirmek için MTT testi kullanılmıştır. In vitro çalışmalar sonucunda optimum formülasyon belirlendikten sonra in vivo değerlendirme aşamasına geçilmiştir. In vivo çalışmalar kapsamında ise sıçanlarda sinir greft prefabrikasyonu gerçekleştirmek amacıyla, siyatik sinirin trifikasyonunun distalinde tibial ve peroneal sinirlerde epinöral pencere açılarak, üç ayrı deney grubunda çalışılmıştır. VEGF’in ELISA ile kanda kantitatif analizi ve yürüme yolu analizi yapılmıştır. Ven greftlerinin histolojik değerlendirmeleri ışık mikroskobu ve TEM analizi ile gerçekleştirilmiştir. Işık mikroskobunda incelenen kesitlerde juguler ven içerisinde miyelinli sinir fibrillerin sayısı ve ortalama çapları belirlenmiş, TEM analizi ile akson ve miyelin kılıfının yapısı incelenmiştir. Sonuç olarak, VEGF yüklü mikroküreler hazırlanmış ve otolog ven kullanılarak sinir greft prefabrikasyonu gerçekleştirilmiştir.Anahtar kelimeler: Kontrollü salım, mikroküre, PLGA, sinir greft prefabrikasyonu, VEGFSUMMARYIn Vitro and in Vivo Evaluation of Vascular Endothelial Growth Factor Loaded Poly (Lactic-co-Glycolic Acid) MicrospheresVEGF, a polypeptide growth factor, is a critical organiser of vascular development due to its ability to regulate proliferation, migration, specialization and survival of endothelial cells. VEGF acts a crucial role on peripheral nerve regeneration by direct effects on axonal outgrowth, neurons, dendrites and survival and proliferation of “Schwann” cells and also increases regeneration by angiogenesis. The aim of this study was to control the release of VEGF from VEGF loaded PLGA microspheres and produce nerve graft prefabrication on rats. In in vitro studies, after the preparation of VEGF loaded PLGA microspheres, the size and SEM study were done and also in vitro release properties were conducted with ELISA. For evaluation of the cytotoxicity of the formulations and proliferation effect of VEGF, MTT test was performed. According to the in vitro studies, optimum formulation was determined and in vivo evaluation stage was conducted. In in vivo studies, epineural window was opened at the distal side of the siatical nerve trification and three separate groups were studied in order to fulfil nerve graft prefabrication. Quantitative analysis of VEGF in blood using ELISA and walking track for rats were done. Histological evaluation of vein grafts were performed with light microscope and TEM analysis. In specimens examined with light microscope, the number and the average diameter of nerve fibers with myelin were determined. The structure of axon and myelin sheath were examined by TEM analysis. In conclusion VEGF loaded microspheres were prepared and nerve graft prefabrication was produced by using autologous vein. Key words: Controlled release, microsphere, nerve graft prefabrication, PLGA, VEGF

Amaç: Bu tez çalışmasında osteomiyelit tedavisi için 3B biyoyazıcı ile vankomisin içeren jelatin metakrilat (JelMA), hyaluronik asit (HA) ve nanosilika (NS) nanokompozit doku iskelelerinin hazırlanması ve in vitro karakterizasyonu amaçlanmıştır. Gereç ve