Cell Adhesion Properties Research Articles

S-Protected Thiolated Chitosan versus Thiolated Chitosan as Cell Adhesive Biomaterials for Tissue Engineering.

Chitosan (Ch) and different Ch derivatives have been applied in tissue engineering (TE) because of their biocompatibility, favored mechanical properties, and cost-effectiveness. Most of them, however, lack cell adhesive properties that are crucial for TE. In this study, we aimed to design an S-protected thiolated Ch derivative exhibiting high cell adhesive properties serving as a scaffold for TE. 3-((2-Acetamido-3-methoxy-3-oxopropyl)dithio) propanoic acid was covalently attached to Ch via a carbodiimide-mediated reaction. Low-, medium-, and high-modified Chs (Ch-SS-1, Ch-SS-2, and Ch-SS-3) with 54, 107 and 140 μmol of ligand per gram of polymer, respectively, were tested. In parallel, three thiolated Chs, namely Ch-SH-1, Ch-SH-2, and Ch-SH-3, were prepared by conjugating N-acetyl cysteine to Ch at the same degree of modification to compare the effectiveness of disulfide versus thiol modification on cell adhesion. Ch-SS-1 showed better cell adhesion capability than Ch-SS-2 and Ch-SS-3. This can be explained by the more lipophilic surfaces of Ch-SS as a higher modification was made. Although Ch-SH-1, Ch-SH-2, and Ch-SH-3 were shown to be good substrates for cell adhesion, growth, and proliferation, Ch-SS polymers were superior to Ch-SH polymers in the formation of 3D cell cultures. Cryogels structured by Ch-SS-1 (SSg) resulted in homogeneous scaffolds with tunable pore size and mechanical properties by changing the mass ratio between Ch-SS-1 and heparin used as a cross-linker. SSg scaffolds possessing interconnected microporous structures showed good cell migration, adhesion, and proliferation. Therefore, Ch-SS can be used to construct tunable cryogel scaffolds that are suitable for 3D cell culture and TE.

Effect of surface characteristics of sputtered titanium and niobium thin alloy films on cell growth and adhesion

Titanium (Ti)–niobium (Nb) thin alloy films were prepared by on-chip sputtering. Their surface properties were characterized, and their cell growth and adhesion properties were investigated. Protrusions were observed on the surface of a thin film made of Ti mixed with a small amount of Nb; these protrusions were smaller and more numerous than those on Ti and Nb thin films. Addition of a small amount of Nb enhanced cell adhesion and cell growth compared to those of Ti or Nb thin films. In addition, cell growth and adhesion decreased with an increase in Nb content. Therefore, the stable morphology, negative zeta potential and suitable protrusion size of these Ti–Nb thin alloy films enhance cell adhesion and cell growth on their surfaces.

Development of cultivable alginate fibers for an ideal cell-cultivated meat scaffold and production of hybrid cultured meat

Slaughtering animals for meat pose several challenges, including environmental pollution and ethical concerns. Scaffold-based cell-cultivated meat has been proposed as a solution to these problems, however, the utilization of animal-derived materials for scaffolding or the high cost of production remains a significant challenge. Alginate is an ideal material for cell-cultivated meat scaffolds but has poor cell adhesion properties. To address this issue, we achieved 82 % cell adhesion coverage by controlling the specific structure generated during the ionic crosslinking process of alginate. Post 11 days of culture; we evaluated cell adhesion, differentiation, and aligned cell networks. The cell growth increased by 12.7 % compared to the initial seeding concentration. Finally, we created hybrid cell-cultivated meat by combining single-cell protein from mycelium and cell-cultivated meat. This is non-animal based, edible, cost-effective, and has a desirable texture by blending cell-cultivated meat with a meat analogue. In summary, the creation of improved alginate fibers can effectively tackle various obstacles encountered in the manufacturing of cell-cultivated meat. This includes enhancing cell adhesion, reducing costs, and streamlining the production procedure.

Universal and One-Step Modification to Render Diverse Materials Bioactivation.

Bioactive materials that can support cell adhesion and tissue regeneration are greatly in demand in clinical applications. Surface modification with bioactive molecules is an efficient strategy to convert conventional bioinert materials into bioactive materials. However, there is an urgent need to find a universal and one-step modification strategy to realize the above transformation for bioactivation. In this work, we report a universal and one-step modification strategy to easily modify and render diverse materials bioactivation by dipping materials into the solution of dibutylamine-DOPA-lysine-DOPA (DbaYKY) tripeptide-terminated cell-adhesive molecules, β-peptide polymer, or RGD peptide for only 5 min. This strategy provides materials with a stable surface modification layer and does not cause an undesired surface color change like the widely used polydopamine coating. This one-step strategy can endow material surfaces with cell adhesion properties without concerns on nonspecific conjugation of proteins and macromolecules. This universal and one-step surface bioactivation strategy implies a wide range of applications in implantable biomaterials.

Homozygous CDH2 variant may be associated with hypopituitarism without neurological disorders.

Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition. The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant. Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing. One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected. A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations. A female patient with hypopituitarism was born from consanguineous parents and had a homozygous, likely pathogenic, CDH2 variant that impairs cell aggregation in vitro. No other likely pathogenic variants in CDH2 were identified in 145 hypopituitarism patients.

Fostering innovation to solve the biomechanics of microbe-host interactions: Focus on the adhesive forces underlying Apicomplexa parasite biology.

The protozoa, Toxoplasma gondii and Plasmodium spp., are preeminent members of the Apicomplexa parasitic phylum in large part due to their public health and economic impact. Hence, they serve as model unicellular eukaryotes with which to explore the repertoire of molecular and cellular strategies that specific developmental morphotypes deploy to timely adjust to their host(s) in order to perpetuate. In particular, host tissue- and cell-invasive morphotypes termed zoites alternate extracellular and intracellular lifestyles, thereby sensing and reacting to a wealth of host-derived biomechanical cues over their partnership. In the recent years, biophysical tools especially related to real time force measurement have been introduced, teaching us how creative are these microbes to shape a unique motility system that powers fast gliding through a variety of extracellular matrices, across cellular barriers, in vascular systems or into host cells. Equally performant was this toolkit to start illuminating how parasites manipulate their hosting cell adhesive and rheological properties to their advantage. In this review, besides highlighting major discoveries along the way, we discuss the most promising development, synergy, and multimodal integration in active noninvasive force microscopy methods. These should in the near future unlock current limitations and allow capturing, from molecules to tissues, the many biomechanical and biophysical interplays over the dynamic host and microbe partnership.

Improved functional properties of the potential probiotic Lacticaseibacillus paracasei ItalPN16 growing in cheese whey.

The production of probiotic bacteria requires specific and expensive culture media for maintain their viability and metabolic response during gastro-intestinal transit and cell adhesion process. The aim of this study was to compare the ability of the potential probiotic Laticaseibacillus paracasei ItalPN16 to grow in plain sweet whey (SW) and acid whey (AW), evaluating changes in some probiotic properties related to the culture media. Pasteurized SW and AW were suitable media for L. paracasei growth, since counts above 9 Log CFU/ml were achieved using <50% of the total sugars in both whey samples after 48h at 37°C. The L. paracasei cells obtained from AW or SW cultures showed increased resistance to pH 2.5 and 3.5, higher autoaggregation, and lower cell hydrophobicity, as compared with the control of MRS. SW also improved the biofilm formation ability and cell adhesion capability to Caco-2 cells. Our results indicate that the L. paracasei adaptation to the SW conditions, inducing metabolic changes that improved its stability to acid stress, biofilm formation, autoaggregation, and cell adhesion properties, which are important functional probiotic properties. Overall, the SW could be considered as low-cost culture medium for sustainable biomass production of L. paracasei ItalPN16.

Progress in the application of 3D-printed sodium alginate-based hydrogel scaffolds in bone tissue repair

In recent years, hydrogels have been widely used in the biomedical field as materials with excellent bionic structures and biological properties. Among them, the excellent comprehensive properties of natural polymer hydrogels represented by sodium alginate have attracted the great attention of researchers. At the same time, by physically blending sodium alginate with other materials, the problems of poor cell adhesion and mechanical properties of sodium alginate hydrogels were directly improved without chemical modification of sodium alginate. The composite blending of multiple materials can also improve the functionality of sodium alginate hydrogels, and the prepared composite hydrogel also has a larger application field. In addition, based on the adjustable viscosity of sodium alginate-based hydrogels, sodium alginate-based hydrogels can be loaded with cells to prepare biological ink, and the scaffold can be printed out by 3D printing technology for the repair of bone defects. This paper first summarizes the improvement of the properties of sodium alginate and other materials after physical blending. Then, it summarizes the application progress of sodium alginate-based hydrogel scaffolds for bone tissue repair based on 3D printing technology in recent years. Moreover, we provide relevant opinions and comments to provide a theoretical basis for follow-up research.

Endothelial Glycocalyx Preservation-Impact of Nutrition and Lifestyle.

The endothelial glycocalyx (eGC) is a dynamic hair-like layer expressed on the apical surface of endothelial cells throughout the vascular system. This layer serves as an endothelial cell gatekeeper by controlling the permeability and adhesion properties of endothelial cells, as well as by controlling vascular resistance through the mediation of vasodilation. Pathogenic destruction of the eGC could be linked to impaired vascular function, as well as several acute and chronic cardiovascular conditions. Defining the precise functions and mechanisms of the eGC is perhaps the limiting factor of the missing link in finding novel treatments for lifestyle-related diseases such as atherosclerosis, type 2 diabetes, hypertension, and metabolic syndrome. However, the relationship between diet, lifestyle, and the preservation of the eGC is an unexplored territory. This article provides an overview of the eGC's importance for health and disease and describes perspectives of nutritional therapy for the prevention of the eGC's pathogenic destruction. It is concluded that vitamin D and omega-3 fatty acid supplementation, as well as healthy dietary patterns such as the Mediterranean diet and the time management of eating, might show promise for preserving eGC health and, thus, the health of the cardiovascular system.

Bacterial Cellulose as Potential Dressing and Scaffold Material: Toward Improving the Antibacterial and Cell Adhesion Properties

Bacterial Cellulose as Potential Dressing and Scaffold Material: Toward Improving the Antibacterial and Cell Adhesion Properties

Dynamic modulation of matrix adhesiveness induces epithelial-to-mesenchymal transition in prostate cancer cells in 3D

Synthetic matrices with dynamic presentation of cell guidance cues are needed for the development of physiologically relevant in vitro tumor models. Towards the goal of mimicking prostate cancer progression and metastasis, we engineered a tunable hyaluronic acid-based hydrogel platform with protease degradable and cell adhesive properties employing bioorthogonal tetrazine ligation with strained alkenes. The synthetic matrix was first fabricated via a slow tetrazine-norbornene reaction, then temporally modified via a diffusion-controlled method using trans-cyclooctene, a fierce dienophile that reacts with tetrazine with an unusually fast rate. The encapsulated DU145 prostate cancer single cells spontaneously formed multicellular tumoroids after 7 days of culture. In situ modification of the synthetic matrix via covalent tagging of cell adhesive RGD peptide induced tumoroid decompaction and the development of cellular protrusions. RGD tagging did not compromise the overall cell viability, nor did it induce cell apoptosis. In response to increased matrix adhesiveness, DU145 cells dynamically loosen cell-cell adhesion and strengthen cell-matrix interactions to promote an invasive phenotype. Characterization of the 3D cultures by immunocytochemistry and gene expression analyses demonstrated that cells invaded into the matrix via a mesenchymal like migration, with upregulation of major mesenchymal markers, and down regulation of epithelial markers. The tumoroids formed cortactin positive invadopodia like structures, indicating active matrix remodeling. Overall, the engineered tumor model can be utilized to identify potential molecular targets and test pharmacological inhibitors, thereby accelerating the design of innovative strategies for cancer therapeutics.

Assessing the protection mechanisms against Enterobacter aerogenes by analyzing aggregation, adherence, antagonistic activity, and safety properties of potentially probiotic strain Lactobacillus brevis G145

The aim of this study was to evaluate the probiotic potential of Lactobacillus brevis G145 isolated from traditional Khiki cheese, analyzing pH and bile resistance, physicochemical properties of the strain (hydrophobicity, auto- and co-aggregation), cholesterol removal, hydroxyl radical scavenging activity, adhesion ability to Caco-2 cells monolayer, and adhesion competition on Enterobacter aerogenes (competition, inhibition and replacement assays). Also, DNase, haemolytic activity, biogenic amine production and antibiotic susceptibility was investigated. L. brevis G145 was resistant to acidic pHs, bile salts, and simulated gastrointestinal conditions, and showed remarkable cell surface hydrophobicity (49.56%), co-aggregation (28.90%), auto-aggregation (34.10%), adhesion (9.40%), cholesterol removal (45.50%), and antioxidant (52.19%) properties. According to the results of well diffusion agar and disc diffusion agar tests, the highest and lowest inhibition zones were accounted for Staphylococcus aureus and Enterobacter aerogenes, respectively. The isolate did not show haemolytic, DNAse, and biogenic amine production properties. It was sensitive to antibiotics erythromycin, ciprofloxacin, and chloramphenicol, and semi-sensitive to imipenem, ampicillin, nalidixic acid, and nitrofurantoin. According to the findings of probiotic tests L. brevis G145 can be used as a in the food industry.

Thiol-Functionalized, Antioxidant, and Osteogenic Mesoporous Silica Nanoparticles for Osteoporosis.

Osteoporosis is a chronic bone disorder characterized by decreased bone mass, leading to brittle bones and fractures. Oxidative stress has been identified as the most profound trigger for the initiation and progression of osteoporosis. Current treatment strategies do not induce new bone formation and fail to address a high level of reactive oxygen species (ROS). Mesoporous silica nanoparticles (MSNs) have been explored in bone tissue regeneration owing to their inherent osteogenic property, but they lack antioxidant and cell adhesion properties, required in such applications. We have developed thiolated, bioactive mesoporous silica nanoparticles (MSN-SH) to address this challenge. MSNs were fabricated using the Stöber method, and 11% of the surface was functionalized post-synthesis with thiol groups using MPTMS to obtain MSN-SH. The particle size measured by the dynamic light scattering technique was found to be around 300 nm. The surface morphology was investigated using HR-TEM, and their physical and chemical properties were characterized using various spectroscopic techniques. They exhibited more than 90% antioxidant activity, neutralized ROS formed in cells, and provided protection against ROS-induced cell damage. The cell viability assay in murine osteoblast precursor cells (MC3T3) showed that MSN-SH is cell-proliferative in nature with 140% cell viability. Osteogenic potential was evaluated by measuring the ALP activities, calcium deposition, and gene expression levels of osteogenic markers, such as RUNX2, ALP, OCN, and OPN, and results revealed that MSN-SH increases calcium deposition and induces osteogenesis through upregulation of osteogenic genes and markers without the involvement of any osteogenic supplements. Besides promoting osteogenesis, MSN-SH was found to inhibit osteoclastogenesis. The nanomaterial was found to be regenerative in nature, and it stimulated migration of osteoblast cells and caused a complete wound closure within 48 h. We were able to achieve a multifunctional nanomaterial by simply modifying the surface. MSNs have been explored for bone tissue engineering/osteoporosis as a composite system incorporating metals, like gold and cerium, or as a nanocarrier loaded with growth factors or active drugs. This study offers a simple and economical method to enhance the existing properties of MSNs and impart new activities by a single-step surface modification. It can be concluded that MSN-SH holds promise as a complementary and alternate treatment for osteoporosis along with the standardized therapy.

Reinforcement of Injectable Hydrogel for Meniscus Tissue Engineering by Using Cellulose Nanofiber from Cassava Pulp.

Injectable hydrogels can be applied to treat damaged meniscus in minimally invasive conditions. Generally, injectable hydrogels can be prepared from various polymers such as polycaprolactone (PCL) and poly (N-isopropylacrylamide) (PNIPAAm). Poly (ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer-diacrylate (PEO-PPO-PEO-DA) is an interesting polymer due to its biodegradability and can be prepared as water-insoluble injectable hydrogel after curing with UV light at low intensity. However, mechanical and cell adhesion properties are not optimal for these hydrogels. For the improved mechanical performance of the injectable hydrogel, cellulose nanofiber (CNF) extracted from cassava pulp was used as a reinforcing filler in this study. In addition, gelatin methacrylate (GelMA), the denatured form of collagen was used to enhance cell adhesion. PEO-PPO-PEO-DA/CNF/GelMA injectable hydrogels were prepared with 2-hydroxy-1-(4-(hydroxy ethoxy) phenyl)-2-methyl-1-propanone as a photoinitiator and then cured with UV light, 365 nm at 6 mW/cm2. Physicochemical characteristics of the hydrogels and hydrogels with CNF were studied in detail including morphology characterization, pore size diameter, porosity, mechanical properties, water uptake, and swelling. In addition, cell viability was also studied. CNF-reinforced injectable hydrogels were successfully prepared after curing with UV light within 10 min with a thickness of 2 mm. CNF significantly improved the mechanical characteristics of injectable hydrogels. The incorporation of GelMA into the injectable hydrogels improved the viability of human cartilage stem/progenitor cells. At optimum formulation, 12%PEO-PPO-PEO-DA/0.5%CNF/3%GelMA injectable hydrogels significantly promoted cell viability (>80%) and also showed good physicochemical properties, which met tissue engineering requirements. In summary, this work shows that these novel injectable hydrogels have the potential for meniscus tissue engineering.

Biochemical, functional and genomic characterization of a new probiotic Ligilactobacillus salivarius F14 from the gut of tribes of Odisha.

Characterization of new potential probiotics is desirable in the field of research on probiotics for their extensive use in health and disease. Tribes could be an unusual source of probiotics due to their unique food habits and least dependence on medications and consumption of antibiotics. The aim of the present study is to isolate lactic acid bacteria from tribal fecal samples of Odisha, India, and characterize their genetic and probiotic attributes. In this context one of the catalase-negative and Gram-positive isolates, identified using 16S rRNA sequencing as Ligilactobacillus salivarius, was characterized in vitro for its acid and bile tolerance, cell adhesion and antimicrobial properties. The whole genome sequence was obtained and analyzed for strain level identification, presence of genomic determinants for probiotic-specific features, and safety. Genes responsible for its antimicrobial and immunomodulatory functions were detected. The secreted metabolites were analyzed using high resolution mass spectroscopy; the results indicated that the antimicrobial potential could be due to the presence of pyroglutamic acid, propionic acid, lactic acid, 2-hydroxyisocaproic acid, homoserine, and glutathione, and the immuno-modulating activity, contributed by the presence of short chain fatty acids such as acetate, propionate, and butyrate. So, to conclude we have successfully characterized a Ligilactobacillus salivarius species with potential antimicrobial and immunomodulatory ability. The health-promoting effects of this probiotic strain and/or its derivatives will be investigated in future.

Co-cultivation effects of Lactobacillus helveticus SNA12 and Kluveromyces marxiensis GY1 on the probiotic properties, flavor, and digestion in fermented milk

This study aimed to evaluate inoculating the lactic acid bacteria Lactobacillus helveticus SNA12 and the yeast Kluyveromyces marxiensis GY1 as starter cultures on milk fermentation. In this study, the probiotic properties of L. helveticus SNA12, K. marxiensis GY1 and co-culture of these two strains (L. helveticus SNA12-K. marxiensis GY1) were investigated, and the results showed that K. marxiensis GY1 had better gastrointestinal tolerance, aggregation, and cell adhesion properties than L. helveticus SNA12. After the co-cultivation of two strains, the presence of K. marxiensis GY1 significantly increased the gastrointestinal tolerance, aggregation, and adhesion characteristics of L. helveticus SNA12. In order to investigate the flavor changes, digestive characteristics, and antioxidant properties following co-cultivation fermentation, the optimal fermentation ratio of 8 %-2% (v/v) and fermentation temperature (37 °C) of L. helveticus SNA12-K. marxiensis GY1 were determined. The results of the electronic nose and electronic tongue showed that L. helveticus SNA12-K. marxiensis GY1 could increase the aroma components of fermented milk, such as terpenes and aromatic substances. Meanwhile, dynamic in vitro rat stomach-duodenum model was used to analyse the changes in the digestion of proteins and peptides (<10 kDa), and the results indicated that co-cultivation fermented milk could be digested faster compared to a single fermentation. Furthermore, the antioxidant capacity of co-cultivation fermented milk was higher than that of single fermentation.

Oriented Fibers Cooperate with DFO to Prevent Tendon Adhesions by Improving the Repair Microenvironment

AbstractTo solve the problem of tendon adhesion after an operation, an anti‐adhesion membrane is designed, which can inhibit the exogenous healing of tendons and promote endogenous healing. Here, poly[3(S)‐methyl‐morpholine‐2,5‐dione‐co‐lactic acid] P(MMD‐co‐LA) containing alanine units is obtained by melt ring‐opening polymerization (ROP). It can effectively reduce the production of acidic degradation products that cause aseptic inflammation. Then a kind of oriented P(MMD‐co‐LA)/deferoxamine (DFO) anti‐adhesion membrane with good mechanical properties, cell adhesion properties, and induced macrophage polarization properties is constructed by electrospinning. In vitro and in vivo studies have shown that oriented fibrous membranes can down‐regulate the expression of inflammatory cytokines. In addition, the fibrous membrane can up‐regulate the expression of angiogenesis‐related genes, namely HIF1‐α, SDF‐1α, and VEGF, by releasing DFO in situ, thus promoting the revascularization of tendon defects and providing nutritional support for endogenous tendon healing. This method provides a new barrier strategy to reduce tendon adhesion through anti‐inflammation combined with vascularization to inhibit exogenous tendon healing while promoting tendon endogenous healing. The results provide essential insights into the corresponding regulation of the tendon healing microenvironment.

Abstract 5808: Integrin-linked kinase regulates Wnt transcriptional activity in platinum resistant ovarian cancer stem cells

Abstract Ovarian cancer (OC) is the most lethal gynecological cancer, characterized by chemo-resistance and fatal tumor recurrence after primary treatment. The metastatic progression is mediated by exfoliation of tumor cells into the peritoneal cavity, the formation of compact OC spheroids, and their implantation onto the overlying peritoneal surface. Spheroid formation is promoted by a change of cell adhesion properties, enhanced secretion of extracellular matrix (ECM) components, such as fibronectin (FN), that stiffen the tumor stroma, promote the aberrant activation of integrins, and recruit the adaptor protein integrin-linked kinase (ILK). ILK drives cytoskeletal assembly and modulates key processes, including survival, invasion, and stemness. However, the functional role of ILK in chemoresistance of ovarian cancer stem cells (OCSCs) remains incompletely understood. We tested the hypothesis that the formation of FN-integrin complexes at the cell membrane promotes survival of OCSCs and supports OC spheroid formation by activating ILK and downstream oncogenic signaling. In OCSCs compared with non-CSC, ILK, FN, and integrin β1 mRNA expression levels were increased (P&amp;lt;0.001) and further enriched in OC spheroids compared with monolayers (P&amp;lt;0.01). ILK blockade with the specific inhibitor cpd-22 suppressed spheroid proliferation and tumor initiating capacity in xenograft mouse model. Furthermore, key oncogenic signaling pathways, in particular decreased β-catenin signaling essential to sustaining cancer cell stemness, were altered in OC spheroids treated with cpd-22. Of the genes examined, expression of Wnt receptor Frizzled 7 (Fzd7) was the mostly highly downregulated in OC spheroids treated with cpd-22, indicating a direct correlation between ILK activation and Wnt signaling. By using co-immunoprecipitation and proximity ligation assay, we demonstrated that ILK co-localizes with Fzd7 in OC spheroids. Mechanistically, treatment of OC spheroids with the combination of carboplatin and ILK-Fzd7 blockade decreased β-catenin signaling, inhibited phospho-Akt at Ser473 and increased levels of cleaved-caspase-3 compared to single agent alone, resulting in apoptosis. By regulating β-catenin signaling, Fzd7 expression and ILK activation are essential for OCSCs survival. Targeting Fzd7-ILK clusters may represent a new therapeutic approach to eradicate OCSC and ultimately improve patient outcomes. Citation Format: Rula Atwani, Virginie Lazar, George Earl Sandusky, Salvatore Condello. Integrin-linked kinase regulates Wnt transcriptional activity in platinum resistant ovarian cancer stem cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5808.

Design of Functional Pluronic-Based Precursors for Tailoring Hydrogel Thermoresponsiveness and Cell-Adhesive Properties

In this study, functional Pluronic F127 precursors were designed and synthesized for the preparation of thermosensitive hydrogels. Using linear Pluronic thioacetate and Pluronic multi-acrylate precursors, F127-based hydrogels were prepared through thioacetate deprotection-mediated Michael-type addition. The properties of these gels were compared to those obtained through free radical crosslinking of F127 diacrylate. Temperature was found to have a clear influence on gel swelling as a result of F127 thermoresponsiveness. The macromolecular architecture and functionality of the precursors were also optimized and characterized in terms of gelation kinetics and drug diffusion. In vitro tests were conducted on fibroblasts and endothelial cells to assess their response to cellular adhesion with Pluronic gels that were functionalized with an RGD peptide or pretreated with serum proteins to promote cell adhesion. This study provides a method for creating tailored hydrogels suitable for various biomedical applications, such as soft-tissue engineering, cell encapsulation, wound healing, and sustained delivery of therapeutic molecules.

Development of cell adhesive and inherently antibacterial polyvinyl alcohol/polyethylene oxide nanofiber scaffolds via incorporating chitosan for tissue engineering

Currently, polyvinyl alcohol (PVA) and polyethylene oxide (PEO), as tissue engineering scaffolds materials, had been widely studied, however the hard issues in cell adhesive and antimicrobial properties still seriously limited their application in biomedical respects. Herein, we solved both hard issues by incorporating chitosan (CHI) into the PVA/PEO system, and successfully prepared PVA/PEO/CHI nanofiber scaffolds via electrospinning technology. First, the hierarchical pore structure and elevated porosity stacked by nanofiber of the nanofiber scaffolds supplied suitable space for cell growth. Significantly, the PVA/PEO/CHI nanofiber scaffolds (the cytotoxicity of grade 0) effectively improved cell adhesion by regulating the CHI content, and presented positively correlated with the CHI content. Besides, the excellent surface wettability of PVA/PEO/CHI nanofiber scaffolds exhibited maximum absorbability at a CHI content of 15 wt%. Based on the FTIR, XRD, and mechanical test results, we studied the semi-quantitative effect of hydrogen content on the aggregated state structure and mechanical properties of the PVA/PEO/CHI nanofiber scaffolds. The breaking stress of the nanofiber scaffolds increased with increasing CHI content, and the maximum value reached 15.37 MPa, increased by 67.61 %. Therefore, such dual biofunctional nanofiber scaffolds with improved mechanical properties showed great potential application in tissue engineering scaffolds.