The myelin sheath is a multilayered glial membrane that surrounds axons providing insulation and rapid propagation of action potentials and contributing to structural support in both the central nervous system (CNS) and the peripheral nervous system (PNS). Therefore, myelin formation plays a crucial role in maintaining the integrity, connectivity, and functionality of the nervous system, as well as neuronal regeneration after injury or damage. Myelination in early developmental stages requires the molecular and mechanical exogenous cues provided mainly by the axons of the neurons, coupling the myelin-generating oligodendrocytes in the CNS and Schwann cells in the PNS. Complementary to early development, adaptive myelination dynamically regulates myelin remodeling in response to neuronal activity, ensuring optimal synaptic function and plasticity. Adaptive myelination is shown to be extremely mechanosensitive, requiring strict spatial constraints, stiffness, and topography for cell plasticity and myelination. Consequently, myelin regeneration is limited after traumatic injury and in demyelinating neurodegenerative diseases such as multiple sclerosis (MS). In addition to the inflammatory niche created around damaged myelin sheath, it is often overlooked that altered mechanical properties of the surrounding tissue are also pivotal in the inhibition of remyelination.This review focuses on the effects of mechanical cues on the polarization and plasticity of myelin generating cells, as well as on the induction of the myelin sheath during normal development and in pathological conditions. It also aims to give insights into potential mechanoepigenetic therapeutic approaches for demyelinating conditions.

Electrospun nanofibers stand out for their remarkable surface area-to-volume ratio, adjustable porosity, and versatile functionalization potential, making them highly attractive for a wide range of applications. These unique characteristics render electrospun nanofibers highly applicable across diverse fields, including healthcare, environmental science, and sensing technologies. Among various nanofiber fabrication techniques, electrospinning remains the most prevalent, enabling the production of ultrafine fibers by applying high voltage to a polymer solution or melt. Through the integration of functional additives, electrospun nanofibers can be tailored for advanced applications such as wound healing, antibacterial protection, UV sensing, and wastewater treatment. This study provides an overview of previous research on electrospun nanofiber surfaces with multifunctional properties. Nanofiber-based materials have been engineered for controlled drug release, promoting efficient tissue healing while reducing the risk of infection. In addition, antibacterial dressings produced with essential oils have been explored for their inherent antimicrobial properties, requiring careful optimization of oil concentration to maintain both efficacy and biocompatibility. Another innovative approach involves UV-sensitive nanofibers embedded with photochromic dyes, enabling real-time UV detection for enhanced skin protection. Furthermore, nanofiber surfaces have shown great potential in environmental applications, particularly for the efficient adsorption of textile dyes from wastewater. These results highlight the remarkable versatility of electrospun nanofibers and their transformative impact across multiple fields. Moving forward, further research should aim to refine nanofiber properties to maximize their performance and broaden their applicability in emerging technologies.

The design of this study was based on donepezil, a selective acetylcholinesterase (AChE) inhibitor used in the treatment of AD, consisting of an 1-indanone ring and a benzylpiperidine moiety. For this purpose, the 1-indanone ring was replaced with a 2-indolinone ring and new hybrid compounds were designed by connecting the benzylpiperidine residue to the 2-indolinone ring via the thiosemicarbazone bridge. Based on the results of in silico studies, 29 new 2-indolinone benzylpiperidine-thiosemicarbazone hybrid compounds (10a-n and 11a-o) were selected and synthesized. The in vitro anti-cholinesterase (ChE) activities of the compounds were determined and compared with donepezil (IC50 = 0.44 μM for AChE and IC50 = 4.70 μM for BuChE). Compound 11e showed the strongest inhibition (IC50 = 0.91 μM for AChE and IC50 = 30.97 μM for BuChE), while compounds 11a, 11b, 11d, 11g, 11k, 11l and 11n also displayed strong AChE inhibitory activity (range of IC50 = 1.15-3.13 μM). Compounds showed weak or no inhibition against BuChE. The cytotoxic effects of the active compounds were evaluated in HUVEC cell lines, and non-cytotoxic effects were observed for compounds 11b, 11d, 11e and 11k. Neuroprotective effect studies of active and non-cytotoxic compounds in HUVEC cells were performed in SH-SY5Y cells exposed to H2O2-induced damage. According to the results, compounds 11e and 11k exhibited significant neuroprotective effects in damaged SH-SY5Y cells, with the compound 11e showing higher protective effect than compound 11k. Compound 11e exhibited a markedly higher permeability across the blood-brain barrier (BBB) model. Compound 11e was selected as the lead candidate based on mechanistic findings. Molecular dynamics simulation of compound 11e was performed on the AChE binding pocket.

Poly(vinylidene fluoride) (PVDF) is widely used in neural tissue engineering for its strong piezoelectric response, yet its nonbiodegradability and environmental persistence limit its clinical translation. Neural regeneration demands scaffolds that not only replicate the extracellular matrix but also deliver bioelectrical cues to guide neuronal growth. Here, we introduce aligned electrospun fibers of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and cellulose acetate (CA) as biodegradable, sustainable alternatives to PVDF for studying how piezoelectricity, surface charge, and nanotopography influence neuronal function. Compared to polycaprolactone (PCL) as a nonpiezoelectric control, the PVDF, PHBV, and CA scaffolds exhibited distinct morphologies and progressively decreasing piezoelectric coefficients. All supported robust adhesion and proliferation of B35 neuronal cells; however, piezoelectric fibers significantly enhanced intracellular Ca2+ influx, neurite elongation, and β3-tubulin expression. Both PVDF and PHBV activated the WNT/GSK3β signaling pathway and downregulated the pro-apoptotic BAX/BCL-2 ratio, suggesting enhanced neuroprotective capacity. Notably, while PVDF induced strong Ca2+-mediated neuronal maturation through piezoelectric stimulation, PHBV elicited additional antiapoptotic effects, likely linked to 3-hydroxybutyrate metabolism. Together, these findings demonstrate that combining nanoscale alignment, surface charge, and intrinsic piezoelectricity generates a bioelectrically active microenvironment conducive to neuronal regeneration. Importantly, PHBV emerges as a sustainable, biodegradable alternative to PVDF, bridging environmental responsibility with functional performance in neural tissue engineering.

Replicating the in vitro properties of tissue barriers-such as the blood-brain barrier, gut, skin, lung, kidney, retina, nasal epithelium, and placenta-is crucial for many applications, including drug screening, studying molecular transport, drug delivery, and disease modeling in preclinical studies. Organ-on-a-chip (OoC) platforms are advanced three-dimensional (3D) in vitro models that aim to replicate various aspects of organ functionality within microfluidic systems by providing microenvironments akin to native tissue. When used to model the interface between two different tissue compartments, OoC technology offers a promising platform for more accurately replicating the physiology and pathophysiology of various tissue barriers in the body. This review focuses on the state-of-the-art biomimetic tissue barrier models, ranging from two-channel tissue barrier-on-a-chip systems with a thin porous membrane to hydrogel-based membrane models. Specifically, it explores the engineering of tissue barrier-on-a-chip platforms, highlighting various fabrication techniques for microfluidic chips and membranes, as well as methods for functional characterization of the engineered tissue barriers. Additionally, we discuss the development of organ-specific barrier models and multi-organ-on-a-chip systems for studying inter-organ communication. Finally, we highlight the current challenges in the field and future directions in advancing tissue barrier modeling using OoC technology.

Intraventricular hemorrhage (IVH) in preterm infants disrupts neurogenesis in the subventricular zone (SVZ), a key neurogenic niche, yet no effective treatments exist. This work develops a human SVZ-on-a-chip model to investigate the inflammatory response in IVH and its impact on neurogenesis. Using this platform, this work examines the effects of red blood cell lysate (RBCL) and hemorrhagic cerebrospinal fluid (CSF) from preterm infants with IVH on SVZ cells. Transcriptomic analysis reveal activation of inflammatory pathways in fetal astrocytes and brain microvascular endothelial cells exposed to hemoglobin isoforms. Notably, interleukin-1B (IL1B) is upregulated following RBCL and hemorrhagic CSF exposure. To probe its role, this work applies an IL1 receptor antagonist, which demonstrate that IL1B has a partially protective influence on neurogenesis. These findings highlight the SVZ-on-a-chip as a powerful tool for studying IVH pathology and emphasize the role of inflammation in regulating neurogenesis. IL1B emerges as a potential therapeutic target, offering new avenues for intervention. This study advances the understanding of IVH and lays the groundwork for developing strategies to protect the developing brain.

Considering the similarity between the invasion processes of cancer cells and embryo implantation, three-dimensional culture models used to study cancer cell invasion can also be applied to embryo implantation studies. In our study, endometrial epithelial cell line (RL95-2) and spheroid-forming trophoblast-like choriocarcinoma cell line (JAR) were cultured on three different biocompatible tissue scaffolds: bacterial cellulose, collagen foam and collagen fibre. These scaffolds are frequently used in cancer cell metastasis and invasion studies, A three-dimensional endometrium-like culture system was established to quantitatively investigate the role of E-cadherin, N-cadherin, Vimentin, α-smooth muscle actin and Syndecan-1 proteins in the type 1 epithelial mesenchymal transition mechanism observed during the invasion step of the implantation process. Based on the findings from the three-dimensional cell culture, the bacterial cellulose scaffold promoted the proliferation of RL95-2 cells and delayed JAR spheroid formation. The collagen foam scaffold favored the proliferation of RL95-2 cells and accelerated JAR spheroid formation. The collagen fibre scaffold is important for supporting cell topography and, when combined with collagen foam, may offer a potential solution for investigating 3D endometrium-like culture systems. Immunocytochemical and immunofluorescence analyses showed that scaffolds modulate the invasion process by affecting the expression of epithelial mesenchymal transition proteins in cells. The findings suggest that different tissue scaffolds can produce varying effects in endometrium-like culture systems, and combinations of these materials may yield more effective results in future studies. This research represents a critical step in studying cell behavior in 3D culture systems and elucidates the mechanism of endometrial invasion.

Amaç: İnvazyon, embriyonun uterus epiteline implantasyonu gibi normal gelişim sürecinde olabildiği gibi kanser hücrelerinin yayılması gibi patolojik olaylarda da görülmektedir. Kanser hücrelerinin invazyon mekanizmalarını anlayabilmek için, hücreleri in vivo ortamlarına yakın bir ortamda araştırmak gerekmektedir. Bu çalışmanın amacı, kanser hücrelerinin invazyon araştırmalarında kullanılabilecek in vivo ortamı taklit eden yeni bir in vitro kültür ortamının geliştirilmesidir. Gereç ve Yöntem: İnsan metastatik meme adenokarsinom (M4A4) ve insan primer kolon karsinoma (HCT-116) hücre dizileri kültüre edilmiştir. İki farklı biyouyumlu doku iskelesi amacıyla bakteriyal selüloz ve kollajen köpük kullanılmıştır. Hücreler doku iskelelerine ekildikten sonra 3D kanser invazyon kültür modelleri oluşturulmuştur. Hücre morfolojisi değerlendirilmiş, Hematoksilen-Eozin boyasıyla histolojik incelemeler yapılmıştır. Bulgular: M4A4 hücreleri, bakteriyel selüloz iskelelerinde fibroblastik morfolojiyi korurken, kollajen köpük iskelelerinde kümelenip çoğalmıştır. HCT-116 hücreleri ise bakteriyel selüloz iskelelerinde yoğun kümelenme ve çoğalma, kollajen köpük iskelelerinde ise fibroblastik morfoloji sergilemiştir. Histolojik incelemeler, HCT-116 hücrelerinin bakteriyel selüloz iskelelerinde, M4A4 hücrelerinin ise kollajen köpük iskelelerinde daha yüksek invazyon ve koloni oluşumu gösterdiğini ortaya koymuştur. Sonuç: Çalışmanın bulguları, iskele seçiminin kanser araştırmalarında hücre davranışı ve çoğalması üzerindeki önemli etkisini vurgulamaktadır. Histolojik sonuçlar, bakteriyel selüloz ve kollajen köpük iskelelerinin farklı kanser hücre hatlarıyla etkileşimlerini ve invaziv davranışlarını etkilediğini göstermektedir. Bu bilgiler, kanser hücresi etkileşimlerinin ve davranışlarının karmaşıklığını anlamak ve incelemek için özel iskele seçimine duyulan ihtiyacı vurgulamaktadır.

Tissue engineering offers a promising route to treat cartilage damage caused by trauma or aging due to factors that limit regenerative capacity, such as tissue avascularity, limited nerve fiber distribution, and low cell-to-matrix ratio. It aims to repair hyaline cartilage by introducing chondrocytes or chondrocyte-differentiated stem cells within biocompatible scaffold. This study aimed to develop a composite tissue scaffold with enhanced mechanical strength and the ability to mimic the extracellular matrix of cartilage tissue by forming chitosan and γ-polyglutamic acid (γ-PGA) polyelectrolyte complexes (PECs) in shredded bacterial cellulose (BC). PECs at C:P molar ratios of 30:70, 50:50, and 70:30 were combined with BC at 0.25% and 0.5% w/v. FTIR confirmed characteristic peaks of BC, chitosan, and γ-PGA in the scaffolds. Water-holding capacity (WHC) increased significantly in the BCn-50P50 scaffolds. BC incorporation modulated PEC pore size and distribution most prominently in C30P70 and C70P30, while, overall, scaffolds exhibited a predominant pore-size range of 50-300 μm. Mechanical testing showed bidirectional reinforcement: PECs enhanced the elastic modulus of the BC, and, conversely, BC increased the elastic modulus of PECs. In vitro, all composite scaffolds were biocompatible and BC0.5-C50P50 scaffolds exhibited the best chondrogenic differentiation at day 7 compared to control (p = 0.0015). To our knowledge, this is the first composite scaffold in which PEC forms within BC nanofibers. The composites improved mechanical performance and WHC, expand surface area for cell adhesion, and support chondrogenic differentiation of mesenchymal stem cells.

The porous structure of scaffolds is critical in facilitating cellular activities such as mass transport, cell migration, and vascularization. The pore size and porosity of the scaffold need to be adjusted according to the specific tissue to enable long-term cultivation in vitro. Therefore, selecting the method to be used in the porosity characterization is critical. In addition to analyzing pore characteristics, micro-computed tomography (Micro-CT) can assess parameters such as the degree of anisotropy, interconnectivity, and hydroxyapatite (HAp) density in bone tissue scaffolds, providing advantages over alternative methods. In this study, a bacterial cellulose-HAp scaffold was fabricated, and its porosity, pore distribution, wall thickness distribution, surface area, degree of anisotropy, and HAp density were characterized. Additionally, 3D models of the scaffold were generated using Micro-CT imaging. The findings of this study demonstrate that Micro-CT is an effective tool for measuring these critical parameters in soft, foam, or flexible scaffolds without causing structural damage. The advantages of this technique over alternative methods are also emphasized. Upon examining the Micro-CT results of the scaffolds designed for bone tissue engineering, it was found that the pore sizes predominantly ranged from 90 to 150 μm, with a maximum pore size of 320 μm. The porosity was approximately 85

Bacterial cellulose (BC) is a biomaterial extensively studied in tissue engineering due to its favorable properties. Porosity, biocompatibility, biodegradability and mechanical durability are essential material properties for scaffold use in tissue engineering. This study aims to fabricate porous scaffolds using a moldable and degradable BC-HAp composite for bone tissue engineering. BC was produced by Komagataeibacter sucrofermentans under static culture conditions. The harvested BC membranes were purified and then mechanically shredded. BC oxidation was performed using different sodium periodate concentrations (0.05–0.5 M) and treatment times (0.5–12 h). Oxidized BCs (oxBC) were modified with hydroxyapatite (HAp), then were moulded, lyophilized, and characterized. The degradability of the scaffolds was determined for 45 days. Cytotoxic analysis of oxBC scaffolds was carried out for 7 days using the L929 fibroblast cell line. The oxidation degrees of the shredded BC samples were between 6.75 and 81%, which increased in line with the increasing concentration and application time of periodate. The scaffolds prepared using oxidized cellulose for 30 and 60 min (oxBC 30 and oxBC 60 ) preserved their integrity, These scaffolds showed a weight loss of 9% and 14% in 45 days, respectively. The pore distribution was between 50 and 450 µm and concentrated in the 50–150 µm range. The compression moduli were 88.72 kPa and 138.88 kPa for oxBC 30 -HAp and oxBC 60 -HAp, respectively. It was determined that oxBC did not show a significant difference in cell viability compared to the control groups and was not cytotoxic. In conclusion, degradable and more porous bone scaffolds were fabricated using mouldable oxBC.

Chemobrionic systems have attracted great attention in material science for development of novel biomimetic materials. This study aims to design a new bioactive material by integrating biosilica into chemobrionic structure, which will be called biochemobrionic, and to comparatively investigate the use of both chemobrionic and biochemobrionic materials as bone scaffolds. Biosilica, isolated from Amphora sp. diatom, was integrated into chemobrionic structure, and a comprehensive set of analysis was conducted to evaluate their morphological, chemical, mechanical, thermal, and biodegradation properties. Then, the effects of both scaffolds on cell biocompatibility and osteogenic differentiation capacity were assessed. Cells attached to the scaffolds, spread out, and covered the entire surface, indicating the absence of cytotoxicity. Biochemobrionic scaffold exhibited a higher level of mineralization and bone formation than the chemobrionic structure due to the osteogenic activity of biosilica. These results present a comprehensive and pioneering understanding of the potential of (bio)chemobrionics for bone regeneration.

A series of tacrine-donepezil hybrids were synthesized as potential multifunctional anti-Alzheimer's disease (AD) compounds. For this purpose, tacrine and the benzylpiperidine moiety of donepezil were fused with a hydrazone group to achieve a small library of tacrine-donepezil hybrids. In agreement with the design, all compounds showed inhibitory activity toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values in the low micromolar range. Kinetic studies on the most potent cholinesterase (ChE) inhibitors within the series showed a mixed-type inhibition mechanism on both enzymes. Also, the docking studies indicated that the compounds inhibit ChEs by dual binding site (DBS) interactions. Notably, tacrine-donepezil hybrids also exhibited significant neuroprotection against H2O2-induced cell death in a differentiated human neuroblastoma (SH-SY5Y) cell line at concentrations close to their IC50 values on ChEs and showed high to medium blood-brain barrier (BBB) permeability on human cerebral microvascular endothelial cells (HBEC-5i). Besides, the compounds do not cause remarkable toxicity in a human hepatocellular carcinoma cell line (HepG2) and SH-SY5Y cells. Additionally, the compounds were predicted to also have good bioavailability. Among the tested compounds, H4, H16, H17, and H24 stand out with their biological profile. Taken together, the proposed novel tacrine-donepezil scaffold represents a promising starting point for the development of novel anti-ChE multifunctional agents against AD.

Parkinson’s Disease (PD), which exhibits a rapidly developing pathology, is one of the most devastating neurodegenerative diseases. To understand its molecular and cellular mechanisms and to attain a truly effective treatment, it is essential to develop standard, rapid, and reliable in vitro testing platforms for diseases. Classical two-dimensional (2D) cell culture is the starting point for the study of PD diagnosis and treatment. However, 2D grown cells do not exhibit the physiological properties of native tissues and provide limited data for testing drugs in vitro and understanding the mechanisms of diseases. Therefore, realistic 3D models similar to human physiology are required. In this study, the 2D and 3D PD modeling potentials of two cell lines (SHSY5Y and PC12), which are frequently used in neural tissue engineering studies, were compared. PD models generated by SHSY5Y and PC12 cells were evaluated by lactate dehydrogenase (LDH), Live&Dead, immunofluorescence, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses. It was determined that PC12 cells had weaker adherence properties than SHSY5Y cells, and therefore, SHSY5Y cells had higher microtissue formation potential. PC12 cells completely lost their dopaminergic properties in 3D conditions, whereas 6-OHDA applied SHSY5Y microtissues showed PD markers related to neurotoxicity. A practical and useful 3D disease model reflecting the characteristics of PD with SHSY5Y cells is presented.

The induction of regeneration in the musculoskeletal system with tissue-engineered grafts has been seen as a promising solution to the problems associated with autografts and allografts. Tissue engineering has the potential to develop the needed musculoskeletal tissue from the patient's own cells on 3D scaffolds. However, due to their load bearing characteristics and high mechanical demands associated with them in their physiological settings, successful and reproducible development of musculoskeletal tissues in vitro and their controllable functionality depend on optimizing appropriate mechanical microenvironment, as well as the biochemical factors, during in vitro culture time. Bioreactors provide dynamic mixing of the culture medium by convection, creating a controlled mass transfer. Controlling the mass transfer enables the cells in the tissue-engineered constructs to reach their nutrient and oxygen needs more easily in a 3D structure. In addition, the flow dynamics provided by bioreactors mimic the interstitial flow between blood and lymphatic vessels in musculoskeletal tissues. Furthermore, other external mechanical stimuli imposed by the correct design of bioreactors simulate the stresses the musculoskeletal tissues are exposed to during their physiological functions. Mechanical stimulation is crucial for the governance of mechanotransduction pathways that regulate the relevant cell behavior. In this chapter, musculoskeletal system tissue engineering examples performed in different types of bioreactors and the physical basis of the bioreactor design are discussed with examples, with special emphasis on stress type versus cellular behavior approach.

Xylometazoline is a well-established nasal decongestant that has been used alone and in combination with dexpanthenol as an over the counter (OTC) medicine. Considering the possibility of further improvement of xylometazoline nasal formulations, hyaluronic acid (HA) was evaluated as an additional ingredient. The aim of this study was to investigate the permeation, mucosal retention, and mucoadhesion properties of a new xylometazoline-HA [Xylo-HA] formulation ex vivo and to explore the potential benefits of incorporating HA in the formulation in vitro. Sheep nasal mucosa was used in the ex vivo study, where Xylo-HA was compared with xylometazoline alone [Xylo-Mono], and in combination with dexpanthenol [Xylo-Dex] to understand the impact of formulation changes. The permeation of xylometazoline was generally low (Xylo-Mono 11.14 f 4.75 %, XyloHA 14.57 f 5.72 % and Xylo-Dex 11.00 f 3.05 % of the applied dose). The steady state fluxes of xylometazoline were determined as 12.64 f 3.52 mu g/cm2h, 2 h, 14.94 f 3.38 mu g/cm2h 2 h and 12.19 f 2.05 mu g/cm2h 2 h for Xylo-Mono, Xylo-HA and Xylo-Dex, respectively. No significant differences were observed between the formulations in the permeation nor mucosal retention studies (p > 0.05 for all), while Xylo-HA exhibited superior mucoadhesive proprieties (p < 0.05 for all). The effects on wound healing and barrier integrity of the three xylometazoline formulations were tested in vitro on HaCaT cells. To better elucidate the role of HA, an additional HA formulation without xylometazoline was prepared (HA-Mono). A scratch test was performed to evaluate wound healing, revealing that the test formulations did not achieve complete wound closure within 72 h and demonstrated a similar effect at the end of the testing period. To assess the effect on barrier integrity, cells were treated for 5 days with daily measurements of transepithelial electrical resistance (TEER). At the end of the experiment, Xylo-Dex showed a moderate 14 % increase in TEER, while Xylo-Mono did not significantly affect this parameter. TEER rose by 951 % in the Xylo-HA, and by 10497 % in the HA group, suggesting that incorporating HA led to enhanced barrier function. Further clinical studies are recommended to better understand the clinical implications and efficacy of the Xylo-HA formulation, with particular focus on the role of HA.

Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell aging is oxidative stress and it is known to have a role in idiopathic pulmonary fibrosis. In this paper, the protective effect of the E-CG-01 (3,4-lacto-cycloastragenol) molecule in terms of its antioxidant properties was evaluated in the bleomycin induced mice lung fibrosis model. Bleomycin sulfate was administered as a single dose (2.5 U/kg body weight) intratracheally to induce lung fibrosis. E-CG-01 was administered intraperitoneally in three different doses (2 mg/kg/day, 6 mg/kg/day, and 10 mg/kg/day) for 14 days, starting three days before the bleomycin administration. Fibrosis was examined by Hematoxylin-Eosin, Masson Trichrome, and immunohistochemical staining for TGF-beta1, Type I collagen Ki-67, and gama-H2AX markers. Activity analysis of catalase and Superoxide dismutase enzymes, measurement of total oxidant, total glutathione, and Malondialdehyde levels. In histological analysis, it was determined that all three different doses of the molecule provided a prophylactic effect against the progression of fibrosis compared to the bleomycin control group. However, it was observed that only the molecule applied in the high dose decreased the total oxidant stress level. Lung weight ratio increased in the BLM group but significantly reduced with high-dose E-CG-01. E-CG-01 at all doses reduced collagen deposition, TGF-β expression, and Ki-67 expression compared to the BLM group. Intermediate and high doses of E-CG-01 also significantly reduced alveolar wall thickness and edema formation. These findings suggest that E-CG-01 has potential therapeutic effects in mitigating lung fibrosis through its antioxidant properties.

Neurodegeneration is a catastrophic process that develops progressive damage leading to functional and structural loss of the cells of the nervous system and is among the biggest unavoidable problems of our age. Animal models do not reflect the pathophysiology observed in humans due to distinct differences between the neural pathways, gene expression patterns, neuronal plasticity, and other disease-related mechanisms in animals and humans. Classical in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting the complex pathophysiology of neurodegenerative diseases. Today, modern, engineered techniques are applied to develop multicellular, intricate in vitro models and to create the closest microenvironment simulating biological, biochemical, and mechanical characteristics of the in vivo degenerating tissue. In THIS review, the capabilities and shortcomings of scaffold-based and scaffold-free techniques, organoids, and microfluidic models that best reflect neurodegeneration in vitro in the biomimetic framework are discussed.

Cancer is still the leading cause of death in the world despite the developing research and treatment opportunities. Failure of these treatments is generally associated with cancer stem cells (CSCs), which cause metastasis and are defined by their resistance to radio- and chemotherapy. Although known stem cell isolation methods are not sufficient for CSC isolation, they also bring a burden in terms of cost. The aim of this study is to develop a high-efficiency, low-cost, specific method for cancer stem cell isolation with magnetic functional nanoparticles. This study, unlike the stem cell isolation techniques (MACS, FACS) used today, was aimed to isolate cancer stem cells (separation of CD133+ cells) with nanoparticles with specific affinity and modification properties. For this purpose, affinity-based magnetic nanoparticles were synthesized and characterized by providing surface activity and chemical reactivity, as well as making surface modifications necessary for both lectin affinity and metal affinity interactions. In the other part of the study, synthesized and characterized functional polymeric magnetic nanoparticles were used for the isolation of CSC from the human osteosarcoma cancer cell line (SAOS-2) with a cancer stem cell subpopulation bearing the CD133 surface marker. The success and efficiency of separation after stem cell isolation were evaluated via the MACS and FACS methods. As a result, when the His-graft-mg-p(HEMA) nanoparticle was used at a concentration of 0.1 µg/mL for 106 and 108 cells, superior separation efficiency to commercial microbeads was obtained.