Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Development of Self-Assembled Peptide Hydrogels Containing Matrix-Metalloproteinase Degradable Motifs for 3D Lung Cancer Models(Royal Society of Chemistry, 2026) Tarim, Burcu Sirma; Tamburaci, Sedef; Top, AybenHydrogel-forming peptides, including matrix metalloproteinase (MMP)-degradable motifs, have been employed to investigate cell-extracellular matrix interactions in vitro. However, their potential in 3D cancer models has been explored only in a few studies. In this study, we used modified MMP-2 degradable motifs (VSLRA or ASLRA) in the design of EDP1 (RVSLRADARVSLRADA) and EDP2 (RASLRADARASLRADA) peptide hydrogelators. The peptides self-assembled into nanofibrillar hydrogels with storage moduli between similar to 300 and similar to 400 Pa. MMP-2 degradation properties of the peptides were confirmed, and a slightly higher MMP-2 responsiveness of the EDP1 hydrogel was observed. The hydrogels were used in the encapsulation of A549 lung adenocarcinoma cancer cells and MRC-5 human lung fibroblast cells. The designed hydrogels supported the proliferation of these cells with high viability and induced cluster formation of encapsulated A549 cells similar to that observed with the RADA hydrogel. However, the hydrogel network structure affected the morphology of the migrated cells in the absence of curcumin. The addition of curcumin decreased the migration and invasion of A549 cells, resulting in a round cell morphology independent of the hydrogel matrices. Anticancer drug tests indicated that cell viability after drug treatment was higher in the 3D hydrogels than in 2D cultures. It was also confirmed that the combinational therapy of doxorubicin and curcumin decreased the cell proliferation and colonization to a greater extent compared to doxorubicin monotherapy. Thus, the hydrogels developed in this study can be used for 3D cancer models or other tissue engineering applications as an alternative to the RADA hydrogel by exploiting the MMP-2 degradation properties.Article Citation - WoS: 2Citation - Scopus: 2Integration of Leu-Asp Cell Attachment Motif Into Self-Assembling Peptide Sequences for Nanofibrillar Hydrogel Formation in Wound Healing(Amer Chemical Soc, 2025) Tarim, Burcu Sirma; Sırma Tarım, Burcu; Tamburaci, Sedef; Top, Ayben; Uysal, Berk; Top, AybenFunctionalizing peptide sequences with cell adhesion motifs enhances their cellular bioactivity. Numerous studies have focused on incorporating the Arg-Gly-Asp (RGD) motif into peptide hydrogels; however, the integration of other bioactive domains has yet to be comprehensively investigated. In this study, one of the essential fibronectin-derived cell-binding domains, Leu-Asp-Val (LDV), was integrated into the self-assembling peptide to obtain extracellular matrix (ECM)-mimetic nanofibrillar hydrogelators. IBP1A (NH2-KLDVKLDVKLKV-CONH2) and IBP1B (NH2-KLDVKLDVKLDV-CONH2) peptides were designed accordingly. These peptides self-assemble into hydrogels in phosphate-buffered saline (PBS) at pH 7.4 and deionized water at neutral pH with storage modulus values between similar to 200 and similar to 2000 Pa. Flow curves and the cyclic strain sweep data confirmed that the hydrogels have shear thinning, injectability, and self-healing properties. Flexible nanofibrillar morphology was observed in the TEM images. Nanofibril widths of IBP1A and IBP1B networks were measured as 8.2 +/- 1.1 and 4.5 +/- 0.8 nm, respectively. In vitro tests were also conducted to evaluate these peptides in wound healing applications. The IBP1A peptide with a +3 charge at neutral pH exhibited modest antibacterial activity against Gram (+) and Gram (-) bacteria. In vitro cell culture experiments show that the IBP1A and IBP1B hydrogels promoted the growth of fibroblast cells and glycosaminoglycan secretion compared with the KLDL12 control peptide, which does not contain the LDV motif. The designed hydrogels induced cell attachment within 72 h by altering the cell morphology similar to their natural 3D microenvironment, whereas cells exhibited spindle-like morphology on the KLDL12 hydrogel and tissue culture polystyrene (TCP). Moreover, IBP1B accelerated in vitro wound healing by facilitating fibroblast migration. These results suggest that these bioactive injectable peptide hydrogels have potential in wound healing and skin tissue regeneration.Article Citation - WoS: 2Citation - Scopus: 2Fabrication of Bioactive Helix Aspersa Extract-Loaded Chitosan-Based Bilayer Wound Dressings for Skin Tissue Regeneration(Amer Chemical Soc, 2024) Perpelek, Merve; Tıhmınlıoğlu, Funda; Tamburaci, Sedef; Karakasli, Ahmet; Tihminlioglu, FundaIn recent years, there has been a notable shift toward exploring plant and animal extracts for the fabrication of tissue engineering structures that seamlessly integrate with the human body, providing both biological compatibility and physical reinforcement. In this particular investigation, we synthesized bilayer wound dressings by incorporating snail (Helix aspersa) secretions, comprising mucus and slime, into chitosan matrices via lyophilization and electrospinning methodologies. A nanofiber layer was integrated on top of the porous structure to mimic the epidermal layer for keratinocyte activity as well as acting as an antibacterial barrier against possible infection, whereas a porous structure was designed to mimic the dermal microenvironment for fibroblast activity. Comprehensive assessments encompassing physical characterization, antimicrobial efficacy, in vitro bioactivity, and wound healing potential were conducted on these bilayer dressings. Our findings revealed that the mucus and slime extract loading significantly altered the morphology in terms of nanofiber diameter and average pore size. Snail extracts loaded on a nanofiber layer of bilayer dressings showed slight antimicrobial activity against Staphylococcus epidermidis and Escherichia coli. An in vitro release study of slime extract loaded in the nanofiber layer indicated that both groups 1 and 2 showed a burst release up to 6 h, and a sustained release was observed up to 96 h for group 1, whereas slime extract release from group 2 continued up to 72 h. In vitro bioactivity assays unveiled the favorable impact of mucus and slime extracts on NIH/3T3 fibroblast and HS2 keratinocyte cell attachment, proliferation, and glycosaminoglycan synthesis. Furthermore, our investigations utilizing the in vitro scratch assay showcased the proliferative and migratory effects of mucus and slime extracts on skin cells. Collectively, our results underscore the promising prospects of bioactive snail secretion-loaded chitosan constructs for facilitating skin regeneration and advancing wound healing therapies.Article Citation - Scopus: 11Fabrication of Helix Aspersa Extract Loaded Gradient Scaffold With an Integrated Architecture for Osteochondral Tissue Regeneration: Morphology, Structure, and in Vitro Bioactivity [1](Amer Chemical Soc, 2023) Tamburaci, Sedef; Perpelek, Merve; Aydemir, Selma; Baykara, Basak; Havitcioğlu, Hasan; Tihminlioğlu, 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.