In Vitro Studies of Genistein Lipophilic Derivatives as Potential UV Radiation Protectors.

The major environmental factor responsible for skin cancer is ultraviolet (UV) radiation, present in sunlight. UV radiation is directly linked to the production of reactive oxygen species (ROS), which accumulate in exposed cells and cause serious damage. The antioxidant systems present in cells cannot always sufficiently neutralize the ROS. Therefore, supplementation with exogenous antioxidants has been proposed. The antioxidant properties of some isoflavones, such as genistein, have already been well-proven. Genistein has limited bioavailability. However, its derivatives, with increased lipophilicity, could facilitate its transfer into cells, where they can expose its antioxidative potential. This study aims to investigate three genistein derivatives, with greater lipophilicity than the native compound, regarding their cytotoxicity, antioxidative properties, and effect on the cell cycle in normal human dermal fibroblasts (NHDF) and a melanoma cancer cell line (Me45). Results showed that lipophilic modification of the genistein molecule changes the biological response of NHDF and Me45 cell lines to UV-C radiation, but the lipophilicity cannot be directly linked with the activity of the compounds. A comparison of the effects of the genistein derivatives on healthy and cancerous cells suggests that their mode of action strongly depends on the type of cell involved.

Gallium octacarboxyphthalocyanine hydroxide as a potential pro-apoptotic drug against cancer skin cells.

Novel anticancer strategies reduce side effects on healthy tissues by elevating the lethal abilities of cancer cells. The development of effective particles with good bioavailability and selectivity remains problematic. For undesirable features, green chemistry is used to synthesize the best compounds, or natural-based particles are improved. Photodynamic therapy (PDT), modelled on phthalocyanines (Pcs), still delivers second-generation sensitizers which are complemented with metal ions, such as Zn2+, Al3+, or Ga3+. Gallium octacarboxyphthalocyanine hydroxide (Ga(OH)PcOC), was designed for skin cancer treatment, and was used as a pro-apoptotic and pro-oxidative agent on normal skin cell lines, fibroblasts (NHDF), and keratinocytes (HaCaT), with promising selectivity against melanoma cancer cells (Me45) in vitro. Compared to the previous reported findings, where the ZnPcOC acted on the skin cell lines at higher doses, the sensitivities to the Ga(OH)PcOC allows for an effective reduction of the sensitizer dose. The effective dose, for a novel Ga(OH)PcOC particle, was significantly reduced from 30 µM to 6 µM on Me45 cancer cells, tested using 24 h MTT viability, as well as cytometric pro-oxidative and pro-apoptotic assays. The promising photosensitizer did not reduce viability in normal fibroblasts and keratinocytes without reactive oxygen species (ROS) elevation or apoptosis induction. The improvement to the previous findings is better Ga-based photosensitizer selectivity against the cancer Me45 cells, then observed in Zn-based compounds.

Pretreatment of Melanoma Cells with Aqueous Ethanol Extract from Madhuca longifolia Bark Strongly Potentiates the Activity of a Low Dose of Dacarbazine.

Madhuca longifolia is an evergreen tree distributed in India, Nepal, and Sri Lanka. This tree is commonly known as Mahua and is used in traditional medicine. It was demonstrated that ethanol extract from the bark of M. longifolia possessed potent cytotoxic activity towards two melanoma cell lines, in contrast to aqueous extract that exhibited no activity. Apart from being selectively cytotoxic to cancer cells (with no activity towards non-cancerous fibroblasts), the studied extract induced apoptosis and increased reactive oxygen species generation in melanoma cells. Additionally, the use of the extract together with dacarbazine (both in non-toxic concentrations) resulted in the enhancement of their anticancer activity. Moreover, the pretreatment of melanoma cells with M. longifolia extract potentiated the activity of a low dose of dacarbazine to an even higher extent. It was concluded that ethanol extract of M. longifolia sensitized human melanoma cells to chemotherapeutic drugs. It can therefore be interesting as a promising source of compounds for prospective combination therapy.

Resistance to death pathway induction as a potential targeted therapy in CRISPR/Cas-9 knock-out colorectal cancer cell lines.

Regulated cell death is a fundamental biological process that plays a crucial role in maintaining tissue homeostasis and eliminating damaged or unnecessary cells. Ferroptosis is an iron-dependent process, characterized by the accumulation of oxidized and damaged lipids, which leads to programmed cell death. Among the ferroptotic pathway genes regulating this process, GPX4, TFRC, ACSL4, FSP1, SLC7A11, and PROM2 could be considered. There are many well-known ferroptotic pathway regulators, which are discussed in this compact review. Cells with tissues of different origin display sensitive or resistant phenotypes to such regulators. In some cases, unexpected changes during cell treatment occurred, suggesting the possibility of regulating the death pathway. We assumed that possible changing of ferro-sensitivity to ferro-resistance in cells, especially in colorectal cancer cell lines, is responded for induced chemoresistance. Using novel techniques, such as CRISPR/Cas-9 genome editing, an induced phenotype "switching" is possible.

Methoxychalcones as potential anticancer agents for colon cancer: Is membrane perturbing potency relevant?

Chalcones are naturally produced by many plants, and constitute precursors for the synthesis of flavons and flavanons. They were shown to possess antibacterial, antifungal, anti-cancer, and anti- inflammatory properties. The goal of the study was to assess the suitability of three synthetic methoxychalcones as potential anticancer agents. In a panel of colon cancer cell lines they were demonstrated to be cytotoxic, proapoptotic, causing cell cycle arrest, and increasing intracellular level of reactive oxygen species. Anticancer activity of the compounds was not diminished in the presence of stool extract containing microbial enzymes that could change the structure of chalcones. Moreover, methoxychalcones interacted strongly with model phosphatidylcholine membranes as detected by differential scanning calorimetry. Metohoxychalcones particularly affected the properties of lipid domains in giant unilamellar liposomes formed from raft-mimicking lipid composition. This may be of importance since many molecular targets for therapy of metastatic colon cancer are raft-associated receptors (e.g., receptor tyrosine kinases). The importance of membrane perturbing potency of methoxychalcones for their biological activity was additionally corroborated by the results obtained by molecular modelling.

The Biocompatibility and Self-Healing Effect of a Biopolymer's Coating on Zn Alloy for Biomedical Applications.

The objective of this study was to formulate dip coatings, incorporating casein, NaOH, and nanocrystalline hydroxyapatite (nanoHAp), with self-healing properties for application on ZnMg3.2 wt.% alloy in the field of biomedical applications. This study hypothesizes that the self-healing mechanism within the layer will impede substrate degradation by progressively filling defects where chlorides from simulated body fluids intervene. Furthermore, it aims to mitigate potential damage effects during the implantation process by the layer's self-healing capabilities. The research focused on the dip-coating process parameters and chemical composition of baths for producing casein coatings on Zn alloy surfaces. This study investigated the impact of casein and NaOH concentration, along with the immersion time of ZnMg3.2 wt.% samples in the coating bath, on the self-healing capability of the coating under simulated human body fluid conditions (Ringer's solution, temperature: 37 °C). Effective technology was developed by selecting specific chemical compositions and immersion times in the coating bath, enhancing the self-healing progress against coating damage in Ringer's solution at 37 °C. The most significant self-healing effect was observed when the ZnMg3.2 wt.% substrate underwent a 1 h immersion in a coating bath containing 2 g of casein, 4 g of NaOH, and 0.1 g of nanoHAp powder. Electrochemical tests were instrumental in determining the optimal casein concentration and immersion time of the Zn alloy in the coating bath.

Compensative Resistance to Erastin-Induced Ferroptosis in GPX4 Knock-Out Mutants in HCT116 Cell Lines.

Ferroptosis results from the accumulation of oxidized and damaged lipids which then leads to programmed cell death. This programmed process is iron-dependent, and as a fundamental biological process, plays a crucial role in tissue homeostasis. The ferroptosis molecular pathway depends on self-regulatory genes: GPX4; TFRC; ACSL4; FSP1; SLC7A11, and PROM2. Some of them were considered here as ferro-sensitive or ferro-resistance markers. We examined the impact of GPX4 gene knock-out, using the CRISPR/Cas-9 technique, on ferroptosis induction in the HCT116 colorectal cancer cell line. The results confirmed that cells lacking the GPX4 gene (GPX4 KO) should be more susceptible to ferroptosis after erastin treatment. However, the decrease in cell viability was not as significant as we initially assumed. Based on the lipid peroxidation markers profile and RT-qPCR gene expression analysis, we revealed the activation of an alternative antioxidant system supporting GPX4 KO cells, mostly for cellular ferroptotic death avoidance. Increased expression of FSP1 and PRDX1 genes in knock-out mutants was associated with their function-recognized here as ferroptosis suppressors. For such reasons, studies on the role of GPX4 and other crucial genes from the ferroptotic pathway should be explored. Despite promising prospects, the utilization of ferroptosis mechanisms in cancer therapy remains at the stage of experimental and in vitro preclinical studies.

Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota-HIF1a/PTBP1 pathway.

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut-lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50-100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial-mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.

Polyurethane-Based Nanocomposites for Regenerative Therapies of Cancer Skin Surgery with Low Inflammatory Potential to Healthy Fibroblasts and Keratinocytes In Vitro.

Nanocomposites based on thermoplastic polyurethanes (TPUs) filled with halloysite nanotubes (HNTs) were studied for their physicochemical and biological properties. Nanocomposites containing halloysite nanotube filler contents of 1 and 2% (E+1 and E+2), respectively, were obtained by extrusion. The newly formed E+1 and E+2 nanomaterials exhibited better flexibility and similar thermal properties compared to neat polyurethane. The use of atomic force microscopy (AFM) and differential scanning calorimetry (DSC) thermogram analysis showed that the distribution of halloysite nanotubes in the polymer matrix is more evenly dispersed in the E+1 nanomaterial, where the grains in the E+2 nanomaterial have a greater tendency to form agglomerates. Mechanical tests have shown that nanocomposites with the addition of HNT are characterized by a higher stress at break and elongation at break compared to neat TPU. The results of cytotoxicity tests suggest that the nanocomposite materials express lower toxicity to normal HaCaT and NHDF than to cancer Me45 cells. Further studies showed that the tested materials induced the expression of proinflammatory interleukins IL6 and IL8 in normal cells, but their overexpression in the cancer cell line resulted in cytostatic effects and proliferation reduction. Such a conclusion suggests the possible application of tested materials for regenerative therapies in cancer surgeries.

Modulating pro-adhesive nature of metallic surfaces through a polypeptide coupling via diazonium chemistry.

The design of biomaterials able to facilitate cell adhesion is critical in the field of tissue engineering. Precise control of surface chemistry at the material/tissue interface plays a major role in enhancing the interactions between a biomaterial and living cells. Bio-integration is particularly important in case of various electrotherapies, since a close contact between tissue and electrode's surface facilitates treatment. A promising approach towards surface biofunctionalization involves the electrografting of diazonium salts followed by the modification of organic layer with pro-adhesive polypeptides. This study focuses on the modification of platinum electrodes with a 4-nitrobenzenediazonium layer, which is then converted to the aminobenzene moiety. The electrodes are further biofunctionalized with polypeptides (polylysine and polylysine/laminin) to enhance cell adhesion. This study also explores the differences between physical and chemical coupling of selected polypeptides to modulate pro-adhesive nature of Pt electrodes with respect to human neuroblastoma SH-SY5Y cells and U87 astrocytes. Our results demonstrate the significant enhancement in cell adhesion for biofunctionalized electrodes, with more amplified adhesion noted for covalently coupled polypeptides. The implications of this research are crucial for the development of more effective and functional biomaterials, particularly biomedical electrodes, which have the potential to advance the field of bioelectronics and improve patients' outcomes.

Synthesis and in vitro cytotoxic activity of dye-linker-macrocycle conjugates with variable linker length and components.

The study investigated the structure-activity relationship of newly synthesized dye-linker-macrocycle (DLM) conjugates and the effect of each component on various biological properties, including cytotoxicity, cellular uptake, intracellular localization, interaction with DNA and photodynamic effects. The conjugates were synthesized by combining 1,8-naphthalimide and thioxanthone dyes with 1,4,7,10-tetraazacyclododecane (cyclen) and 1-aza-12-crown-4 (1A12C4) using alkyl linkers of different lengths. The results revealed significant differences in biological activity among the various series of conjugates. Particularly, 1A12C4 conjugates exhibited notably higher cytotoxicity compared to cyclen conjugates. Conjugation with 1A12C4 proved to be an effective strategy for increasing cellular uptake and cytotoxicity of small-molecule conjugates. In addition, the results highlighted the critical role of linker length in modulating the biological activity of DLM conjugates. It became clear that the choice of each component (dye, macrocycle and linker) could significantly alter the biological activity of the conjugates.

Metabolomics reveals that PS-NPs promote lung injury by regulating prostaglandin B1 through the cGAS-STING pathway.

Nanoplastics have been widely studied as environmental pollutants, which can accumulate in the human body through the food chain or direct contact. Research has shown that nanoplastics can affect the immune system and mitochondrial function, but the underlying mechanisms are unclear. Lungs and macrophages have important immune and metabolic functions. This study explored the effects of 100 nm PS-NPs on innate immunity, mitochondrial function, and cellular metabolism-related pathways in lung (BEAS-2B) cells and macrophages (RAW264.7). The results had shown that PS-NPs exposure caused a decrease in mitochondrial membrane potential, intracellular ROS accumulation, and Ca2+ overload, and activated the cGAS-STING signaling pathway related to innate immunity. These changes had been observed at concentrations of PS-NPs as low as 60 µg/mL, which might have been comparable to environmental levels. Non-target metabolomics and Western Blotting results confirmed that PS-NPs regulated prostaglandin B1 and other metabolites to cause cell damage through the cGAS-STING pathway. Supplementation of prostaglandin B1 alleviated the immune activation and metabolic disturbance caused by PS-NPs exposure. This study identified PS-NPs-induced innate immune activation, mitochondrial dysfunction, and metabolic toxicity pathways, providing new insights into the potential for adverse outcomes of NPs in human life.

P53-response circRNA_0006420 aggravates lung cancer radiotherapy resistance by promoting formation of HUR/PTBP1 complex.

BACKGROUND: p53 wild-type lung cancer cells can develop radiation resistance. Circular RNA (circRNA) consists of a family of transcripts with exclusive structures. circRNA is critical in tumorigenesis and is a potential biomarker or therapeutic target. It is uncertain how circRNA expression and functions are regulated post-radiation in p53 wild-type cancer cells. METHODS: A549 or H1299 cells were divided into p53-wt and p53-KO groups by CRISPR/Cas9; both groups were subjected to 4 Gy ionizing radiation (IR: p53-wt-IR and p53-KO-IR). RNA-seq, CCK8, cell cycle, and other functional and mechanism experiments were performed in vivo. p53 gene knockout mice were generated to test the cell results in vitro. RESULTS: circRNAs were found in differential groups. circRNA_0006420 (IRSense) was upregulated in p53-wt cells but had the same expression level as p53-KO cells after radiation, indicating that p53 silencing prevents its upregulation after IR. In the presence of p53, upregulated IRSense post-radiation induces G2/M arrest by regulating DNA damage repair (DDR) pathway-related proteins. Meanwhile, upregulated IRSense post-radiation aggravates the radiation-induced epithelial-mesenchymal transition (EMT). Interestingly, in the presence of p53, it promotes IRSense/HUR/PTBP1 complex formation resulting in the promotion of the radiation-induced EMT. Moreover, c-Jun regulates the upregulation of p53 transcription after radiation treatment. For these lung cancer cells with p53, upregulated IRSense aggravates lung cancer cell proliferation and increases radiation resistance by interacting with HUR (ElAV-like protein 1) and PTBP1 (polypyrimidine tract-binding protein 1) in the nucleus. CONCLUSIONS: Lung cancer cells retaining p53 may upregulate circRNA_0006420 (IRSense) expression post radiation to form an IRSense/HUR/PTBP1 complex leading to radiotherapy resistance. This study furthers our understanding of the roles of circRNA in regulating the effect of radiotherapy and provides novel therapeutic avenues for effective clinical lung cancer therapies.

Nanoparticles-induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models.

Nanoparticles (NPs) have become one of the most popular objects of scientific study during the past decades. However, despite wealth of study reports, still there is a gap, particularly in health toxicology studies, underlying mechanisms, and related evaluation models to deeply understanding the NPs risk effects. In this review, we first present a comprehensive landscape of the applications of NPs on health, especially addressing the role of NPs in medical diagnosis, therapy. Then, the toxicity of NPs on health systems is introduced. We describe in detail the effects of NPs on various systems, including respiratory, nervous, endocrine, immune, and reproductive systems, and the carcinogenicity of NPs. Furthermore, we unravels the underlying mechanisms of NPs including ROS accumulation, mitochondrial damage, inflammatory reaction, apoptosis, DNA damage, cell cycle, and epigenetic regulation. In addition, the classical study models such as cell lines and mice and the emerging models such as 3D organoids used for evaluating the toxicity or scientific study are both introduced. Overall, this review presents a critical summary and evaluation of the state of understanding of NPs, giving readers more better understanding of the NPs toxicology to remedy key gaps in knowledge and techniques.

Antibacterial coatings for electroceutical devices based on PEDOT decorated with gold and silver particles.

The continuous progression in the field of electrotherapies implies the development of multifunctional materials exhibiting excellent electrochemical performance and biocompatibility, promoting cell adhesion, and possessing antibacterial properties. Since the conditions favouring the adhesion of mammalian cells are similar to conditions favouring the adhesion of bacterial cells, it is necessary to engineer the surface to exhibit selective toxicity, i.e., to kill or inhibit the growth of bacteria without damaging mammalian tissues. The aim of this paper is to introduce a surface modification approach based on a subsequent deposition of silver and gold particles on the surface of a conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting PEDOT-Au/Ag surface is found to possess optimal wettability, roughness, and surface features making it an excellent platform for cell adhesion. By depositing Ag particles on PEDOT surface decorated with Au particles, it is possible to reduce toxic effects of Ag particles, while maintaining their antibacterial activity. Besides, electroactive and capacitive properties of PEDOT-Au/Ag account for its applicability in various electroceutical therapies.

Surface grafting of poly-L-lysine via diazonium chemistry to enhance cell adhesion to biomedical electrodes.

The ability to study and regulate cell behavior at a biomaterial interface requires a strict control over its surface chemistry. Significance of studying cell adhesion in vitro and in vivo has become increasingly important, particularly in the field of tissue engineering and regenerative medicine. A promising surface modification route assumes using organic layers prepared by the method of electrografting of diazonium salts and their further functionalization with biologically active molecules as cell adhesion promoters. This work reports the modification of platinum electrodes with selected diazonium salts and poly-L-lysine to increase the number of sites available for cell adhesion. As-modified electrodes were characterized in terms of their chemical and morphological properties, as well as wettability. In order to monitor the process of cell attachment, biofunctionalized electrodes were used as substrates for culturing human neuroblastoma SH-SY5Y cells. The experiments revealed that cell adhesion is favored on the surface of diazonium-modified and poly-L-lysine coated electrodes, indicating proposed modification route as a valuable strategy enhancing the integration between bioelectronic devices and neural cells.

Glycoconjugates of Mucochloric Acid-Synthesis and Biological Activity.

The pharmacological effects of the presence of a sugar moiety, 1,2,3-triazole ring and silyl groups in the structure of biologically active compounds have been extensively studied in drug design and medicinal chemistry. These components can be useful tools to tailoring the bioavailability of target molecules. Herein we present the study on the impact of the sugar substituent structure and triisopropylsilyl group presence on the anticancer activity of mucochloric acid (MCA) derivatives containing the furan-2(5H)-one or 2H-pyrrol-2-one core. The obtained results clearly indicated that tested compounds caused a significant decrease in cell viability of HCT116 and MCF-7 cell lines. MCF-7 cells indicate serious resistance toward investigated compounds in comparison with HCT116 cell line, it suggests that estrogen-dependent breast cancer cells are significantly less sensitive to the tested derivatives. Depending on the structure of the sugar, the type and site of connection with the furanone or 2H-pyrrol-2-one derivative and the presence of the silyl group, the selectivity of the compound towards cancer cells can be controlled. The obtained results may have an impact on the design of new furanone-based anticancer compounds.

14-Substituted Diquinothiazines as a New Group of Anticancer Agents.

A series of novel double-angularly condensed diquinothiazines with aminoalkyl, amidoalkyl, sulfonamidoalkyl, and substituted phenyl groups was designed, synthesized, and evaluated for their anticancer activity against four selected human tumor cell lines (HTC116, SH-SY5Y, A549, and H1299). The cytotoxicity of the novel diquinothiazines was investigated against BEAS-2B cells. The activities of the compounds were compared to etoposide. Among them, compounds with aminoalkyl and phenyl groups showed excellent broad-spectrum anticancer activity. The most active 14-(methylthiophenyl)diquinothiazine, 3c, showed low cytotoxicity against BEAS-2B cells and high activity against tumor cell lines HTC116, SH-SY5Y, A549, and H1299, with IC50 values of 2.3 µM, 2.7 µM, 17.2 µM, and 2.7 µM, respectively (etopiside 8.6 µM, 3.9 µM, 44.8 µM, and 0.6, respectively). Live long-term microscopic observations of cell survival using the starting molecule M0 were also performed. Flow cytometry showed the proapoptotic effects of the studied diquinothiazines. Inhibition of the cell cycle in the S phase was observed, which is associated with damage to nucleic acids and connected to DNA replication arrest.

Toxicity evaluation of choline ionic liquid-based nanocarriers of pharmaceutical agents for lung treatment.

In vitro cytotoxicity evaluation of linear copolymer (LC) containing choline ionic liquid units and its conjugates with an antibacterial drug in anionic form, that is, p-aminosalicylate (LC_PAS), clavulanate (LC_CLV), or piperacillin (LC_PIP) was carried out. These systems were tested against normal: human bronchial epithelial cells (BEAS-2B), and cancers: adenocarcinoma human alveolar basal epithelial cells (A549), and human non-small cell lung carcinoma cell line (H1299). Cells viability, after linear copolymer LC and their conjugates addition for 72 h, was measured at concentration range of 3.125-100 µg/mL. The MTT test allowed the designation of IC50 index, which was higher for BEAS-2B, and significantly lower in the case of cancer cell lines. The cytometric analyzes, that is, Annexin-V FITC apoptosis assay and cell cycle analysis as well as gene expression measurements for interleukins IL6 and IL8 were carried out, and showed pro-inflammatory activity of tested compounds toward cancer cells, while it was not observed against normal cell line.

Biodegradable Scaffolds for Vascular Regeneration Based on Electrospun Poly(L-Lactide-co-Glycolide)/Poly(Isosorbide Sebacate) Fibers.

Vascular regeneration is a complex process, additionally limited by the low regeneration potential of blood vessels. Hence, current research is focused on the design of artificial materials that combine biocompatibility with a certain rate of biodegradability and mechanical robustness. In this paper, we have introduced a scaffold material made of poly(L-lactide-co-glycolide)/poly(isosorbide sebacate) (PLGA/PISEB) fibers fabricated in the course of an electrospinning process, and confirmed its biocompatibility towards human umbilical vein endothelial cells (HUVEC). The resulting material was characterized by a bimodal distribution of fiber diameters, with the median of 1.25 µm and 4.75 µm. Genotyping of HUVEC cells collected after 48 h of incubations on the surface of PLGA/PISEB scaffolds showed a potentially pro-angiogenic expression profile, as well as anti-inflammatory effects of this material. Over the course of a 12-week-long hydrolytic degradation process, PLGA/PISEB fibers were found to swell and disintegrate, resulting in the formation of highly developed structures resembling seaweeds. It is expected that the change in the scaffold structure should have a positive effect on blood vessel regeneration, by allowing cells to penetrate the scaffold and grow within a 3D structure of PLGA/PISEB, as well as stabilizing newly-formed endothelium during hydrolytic expansion.