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Producing backbone degradable copolymers via free-radical copolymerization is a promising, yet challenging method to develop more sustainable materials for many applications. In this work, we present the copolymerization of 2-methylen-1,3-dioxepane (MDO) with crotonic acid derivative esters. MDO can copolymerize by radical ring-opening polymerization incorporating degradable ester moieties in the polymer backbone, although this can often be difficult due to the very unfavorable reactivity ratios. Crotonic acid derivatives, on the other hand, can be easily produced completely from biomass but are typically very difficult to (co)polymerize due to low propagation rates and very unfavorable reactivity ratios. Herein, we present the surprisingly easy copolymerization between MDO and butyl crotonate (BCr), which shows the ability to form alternating copolymers. The alternating nature of the copolymer was characterized by MALDI-TOF and supported by the reactivity ratios calculated experimentally ( r MDO = 0.105 and r BCr = 0.017). The alternating nature of the copolymers favored the degradability that could be achieved under basic conditions (in 2 h, all chains have molar masses smaller than 2 kg/mol). Last, the work was expanded to other crotonate monomers to expand the portfolio and show the potential of this copolymer family.

Particle size and particle size distribution (PSD) are important properties of polymer latexes because they strongly affect the film formation and the rheological properties of the latexes. Thus, monitoring the particle size is of paramount importance during the production of waterborne polymeric dispersions, for which online/inline measurements of the particle size are required. Herein, turbidity spectroscopy (TUS) is used to measure the particle size of nanoparticles in dispersed media. Calibration curves based on a modified wavelength exponent method are introduced and assessed to monitor the evolution of a broad range of particle sizes in seeded semibatch emulsion polymerizations of methyl methacrylate, butyl acrylate, methacrylic acid (MMA/BA/MAA 51/47/2) terpolymers. It is shown that the wavelength exponent based calibration curves can be successfully used to retrieve the particle size during the polymerization process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bioactive glasses (BGs) arewell known for their successful applications in tissue engineering and regenerative medicine. Recent experimental studies have shown their potential usability in oncology, either alone or in combination with other biocompatible materials, such as biopolymers. Direct contact with BG particles has been found to cause toxicity and death in specific cancer cells (bone-derived neoplastic stromal cells) in vitro. Nanostructured BGs (NBGs) can be doped with anticancer elements, such as gallium, to enhance their toxic effects against tumor cells. However, the molecular mechanisms and intracellular targets for anticancer compositions of NBGs require further clarification. NBGs have been successfully evaluated for use in various well-established cancer treatment strategies, including cancer hyperthermia, phototherapy, and anticancer drug delivery. Existing results indicate that NBGs not only enhance cancer cell death, but can also participate in the regeneration of lost healthy tissues. However, the application of NBGs in oncology is still in its early stages, and numerous unanswered questions must be addressed. For example, the impact of the composition, biodegradation, size, and morphology of NBGs on their anticancer efficacy should be defined for each type of cancer and treatment strategy. Moreover, it should be more clearly assessed whether NBGs can shrink tumors, slow/stop cancer progression, or cure cancer completely. In this regard, the use of computational studies (in silico methods) is highly recommended to design the most effective glass formulations for cancer therapy approaches and to predict, to some extent, the relevant properties, efficacy, and outcomes. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2023 Wiley Periodicals LLC.)

Polymer colloids are complex materials that have the potential to be used in a vast array of applications. One of the main reasons for their continued growth in commercial use is the water-based emulsion polymerization process through which they are generally synthesized. This technique is not only highly efficient from an industrial point of view but also extremely versatile and permits the large-scale production of colloidal particles with controllable properties. In this perspective, we seek to highlight the central challenges in the synthesis and use of polymer colloids, with respect to both existing and emerging applications. We first address the challenges in the current production and application of polymer colloids, with a particular focus on the transition toward sustainable feedstocks and reduced environmental impact in their primary commercial applications. Later, we highlight the features that allow novel polymer colloids to be designed and applied in emerging application areas. Finally, we present recent approaches that have used the unique colloidal nature in unconventional processing techniques., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Competing Interests: Conflicts of interest: the authors declare no conflicts of interest.

Beyond their well-known applications in bone tissue engineering, hydroxyapatite nanoparticles (HAp NPs) have also been showing great promise for improved cancer therapy. The chemical structure of HAp NPs offers excellent possibilities for loading and delivering a broad range of anticancer drugs in a sustained, prolonged, and targeted manner and thus eliciting lower complications than conventional chemotherapeutic strategies. The incorporation of specific therapeutic elements into the basic composition of HAp NPs is another approach, alone or synergistically with drug release, to provide advanced anticancer effects such as the capability to inhibit the growth and metastasis of cancer cells through activating specific cell signaling pathways. HAp NPs can be easily converted to smart anticancer agents by applying different surface modification treatments to facilitate the targeting and killing of cancer cells without significant adverse effects on normal healthy cells. The applications in cancer diagnosis for magnetic and nuclear in vivo imaging are also promising as the detection of solid tumor cells is now achievable by utilizing superparamagnetic HAp NPs. The ongoing research emphasizes the use of HAp NPs in fabricating three-dimensional scaffolds for the treatment of cancerous tissues or organs, promoting the regeneration of healthy tissue after cancer detection and removal. This review provides a summary of HAp NP applications in cancer theranostics, highlighting the current limitations and the challenges ahead for this field to open new avenues for research.

The utilization of bioactive glasses (BGs) in cancer therapy has recently become quite promising; herein, a series of Fe-doped mesoporous 45S5-based BGs (MBGs) were synthesized via the sol-gel method in the presence of Pluronic P123 as a soft template. The physico-chemical and biological properties of the prepared glasses were well-characterized through structural assessments, thermal analyses, and electron microscopic studies. Electrochemical analyses, including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), were also performed to investigate the actual potential of the Fe 2 O 3 -containing MBGs in modulating the Fenton's reaction. The XRD results confirmed the glassy state of the Fe-doped samples before immersion in simulated body fluid (SBF). The prepared Fe-doped MBGs exhibited a particle size in the range of 11-86 nm, surface charge of 27-30 mV, S BET of 95-306 m 2 /g, and M s of 0.08 to 0.2 emu/g. The incorporation of Fe 2 O 3 led to a negligible decrease in the bioactivity of the glasses. The CV analysis indicated that the Fe-doped MBGs could generate H 2 O 2 in a cathodic potential higher than -0.2 V (vs. Ag/AgCl) in the O 2 -saturated Na 2 SO 4 solution. Additionally, the data of the EIS test revealed that the Fe 2 O 3 -doped MBGs could increase the standard rate constant of Electro-Fenton's (EF) reaction up to 38.44 times as compared with the Fe-free glasses. In conclusion, Fe-doped 45S5-derived glasses may be useful in cancer therapy strategies due to their capability of activating Fenton's reaction and subsequent production of reactive oxygen species (ROS) such as • OH free radicals., (Copyright © 2022. Published by Elsevier Inc.)

Lactide-valerolactone copolymers have potential application in the packaging sector. Different copolymers were synthesized, and the kinetics of the copolymerization reactions and the microstructure of the copolymers were analysed. Lactide showed higher reactivity than valerolactone which leads to composition drift through the reaction. Thermal, mechanical and barrier properties of the selected copolymers were studied. Overall, the incorporation of valerolactone results in copolymers with higher ductility than poly(lactide) with intermediate water and oxygen permeability which makes these materials appropriate candidates for use in the packaging sector.

Aims: Glioblastoma (GB) is the most aggressive type of brain tumor. Rapid progression, active angiogenesis, and therapy resistance are major reasons for its high mortality. Elevated expression of members of the vascular endothelial growth factor (VEGF) family suggests that anti-VEGF therapies may be potent anti-glioma therapeutic approaches. Here, we evaluated the anti-tumor activity of cediranib, a pan inhibitor of the VEGF receptors, on GB cells., Materials and Methods: Anti-proliferative effects of cediranib were determined using MTT, crystal-violet staining, clonogenic and anoikis resistance assays. Apoptosis induction was assessed by Annexin V/PI staining and Western blot analysis and aggressive abilities of GB cells were investigated using cell migration/invasion assays and zymography. Small-interfering RNA (siRNA)-mediated Knockdown was used to study resistance mechanisms. The anti-proliferative and apoptotic effects of cediranib in combination with radiotherapy, temozolomide, bevacizumab were also evaluated using MTT, Annexin V/PI staining and Western blot analysis for cleaved PARP-1., Key Findings: Cediranib reduced GB cell proliferation, induced apoptotic cell death and inhibited the aggressive abilities of GB cells. Cediranib synergistically increased the anti-proliferative and apoptotic effects of radiotherapy and bevacizumab and augmented the sensitivity of GB cells to temozolomide chemotherapy. In addition, knockdown of MET and AKT potentiated cediranib sensitivity in cediranib-resistant GB cells., Significance: These findings suggest that cediranib, alone or in combination with other therapeutics, is a promising strategy for the treatment of GB and provide a rationale for further investigation of the therapeutic potential of cediranib for the treatment of this fatal malignancy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

As a phenolic acid compound, caffeic acid (CA) can be isolated from different sources such as tea, wine and coffee. Caffeic acid phenethyl ester (CAPE) is naturally occurring derivative of CA isolated from propolis. This medicinal plant is well-known due to its significant therapeutic impact including its effectiveness as hepatoprotective, neuroprotective and anti-diabetic agent. Among them, anti-tumor activity of CA has attracted much attention, and this potential has been confirmed both in vitro and in vivo. CA can induce apoptosis in cancer cells via enhancing ROS levels and impairing mitochondrial function. Molecular pathways such as PI3K/Akt and AMPK with role in cancer progression, are affected by CA and its derivatives in cancer therapy. CA is advantageous in reducing aggressive behavior of tumors via suppressing metastasis by inhibiting epithelial-to-mesenchymal transition mechanism. Noteworthy, CA and CAPE can promote response of cancer cells to chemotherapy, and sensitize them to chemotherapy-mediated cell death. In order to improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid and p-coumaric acid. Due to its poor bioavailability, nanocarriers have been developed for enhancing its ability in cancer suppression. These issues have been discussed in the present review with a focus on molecular pathways to pave the way for rapid translation of CA for clinical use., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Gene therapy is an emerging and promising strategy in cancer therapy where small interfering RNA (siRNA) system has been deployed for down-regulation of targeted gene and subsequent inhibition in cancer progression; some issues with siRNA, however, linger namely, its off-targeting property and degradation by enzymes. Nanoparticles can be applied for the encapsulation of siRNA thus enhancing its efficacy in gene silencing where chitosan (CS), a linear alkaline polysaccharide derived from chitin, with superb properties such as biodegradability, biocompatibility, stability and solubility, can play a vital role. Herein, the potential of CS nanoparticles has been discussed for the delivery of siRNA in cancer therapy; proliferation, metastasis and chemoresistance are suppressed by siRNA-loaded CS nanoparticles, especially the usage of pH-sensitive CS nanoparticles. CS nanoparticles can provide a platform for the co-delivery of siRNA and anti-tumor agents with their enhanced stability via chemical modifications. As pre-clinical experiments are in agreement with potential of CS-based nanoparticles for siRNA delivery, and these carriers possess biocompatibiliy and are safe, further studies can focus on evaluating their utilization in cancer patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dose-dependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review.

Prostate Cancer is the second cause of cancer-related death in men and development of metastatic castration-resistant prostate cancer (mCRPC) is the major reason for its high mortality rate. Despite various treatments, all patients succumb to resistant disease, suggesting that there is a pressing need for novel and more efficacious treatments. Members of the vascular endothelial growth factor (VEGF) family play key roles in the tumorigenesis of mCRPC, indicating that VEGF-targeted therapies may have potential anti-tumor efficacy in this malignancy. However, due to compensatory activation of other family members, clinical trials with single-targeted VEGF inhibitors were discouraging. Here, we determined the anti-neoplastic activity of Cediranib, a pan-VEGF receptor inhibitor, in the mCRPC cell lines. Anti-growth effects of Cediranib were studied by MTT and BrdU cell proliferation assays and crystal violet staining. Annexin V/PI, radiation therapy and cell motility assays were carried out to examine the effects of Cediranib on apoptosis, radio-sensitivity and cell motility. Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses were conducted to determine the molecular mechanisms underlying the anti-tumor activity of Cediranib. Cediranib decreased cell viability and induced apoptosis via inhibition of the anti-apoptotic proteins. Combination with Cediranib synergistically increased Docetaxel sensitivity and potentiated the effects of radiation therapy. Furthermore, Cediranib impaired cell motility via decrease in the expression of the epithelial-to-mesenchymal transition markers. These findings suggest that Cediranib may have anti-tumor activity in mCRPC cells and warrant further investigation on the therapeutic activity of this pan-VEGF receptor inhibitor in mCRPC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Angiogenesis plays a critical role within the human body, from the early stages of life (i.e., embryonic development) to life-threatening diseases (e.g., cancer, heart attack, stroke, wound healing). Many pharmaceutical companies have expended huge efforts on both stimulation and inhibition of angiogenesis. During the last decade, the nanotechnology revolution has made a great impact in medicine, and regulatory approvals are starting to be achieved for nanomedicines to treat a wide range of diseases. Angiogenesis therapies involve the inhibition of angiogenesis in oncology and ophthalmology, and stimulation of angiogenesis in wound healing and tissue engineering. This review aims to summarize nanotechnology-based strategies that have been explored in the broad area of angiogenesis. Lipid-based, carbon-based and polymeric nanoparticles, and a wide range of inorganic and metallic nanoparticles are covered in detail. Theranostic and imaging approaches can be facilitated by nanoparticles. Many preparations have been reported to have a bimodal effect where they stimulate angiogenesis at low dose and inhibit it at higher doses.

Gastric adenocarcinoma (GAC), the most common malignancy of the stomach, is the fourth most common and the second cause of cancer-related death worldwide. Although HER family plays a cardinal role in tumorigenesis of GAC, trastuzumab is the only approved anti-HER drug for this malignancy and development of resistance to trastuzumab is inevitable. Additionally, single-targeted HER inhibitors have demonstrated limited activity in GAC. Hence, there is a pressing need to devise more efficacious anti-HER therapeutic strategies. Here, we examined the anti-tumor activity of neratinb, a pan-HER inhibitor, on GAC cells. Anti-proliferative effects of neratinib were determined using a cell proliferation assay and crystal violet staining. Annexin V/PI staining, radiation therapy and anoikis resistance and wound healing assays were carried out to examine the effects of neratinib on apoptosis, radio-sensitivity and cell motility, respectively. Quantitative reverse transcription-PCR (qRT-PCR) analyses were applied to further investigate the anti-tumor activity of neratinib. We found that neratinib sensitized GAC cells to 5FU, carboplatin and oxaliplatin. Moreover, we found that neratinib was synergistic with trametinib (an approved MEK inhibitor) and foretinib (a c-MET inhibitor) and potentiated radio-sensitivity of GAC cells. Furthermore, we found that neratinib diminished GAC cell proliferation along with downregulation of FOXM1 and its targets. Additionally, neratinib induced apoptosis along with upregulation of pro-apoptotic and downregulation of anti-apoptotic genes. Treatment with neratinib attenuated invasive ability of GAC cells as shown by reduced anoikis resistance, downregulation of EMT markers, and reduced width in scratch assay. Our findings indicate that neratinib provides the therapeutic potential in the treatment of GAC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bioactive glasses (BGs) are routinely being used as potent materials for hard and soft tissue engineering applications; however, improving their biological activities through surface functionalization and modification has been underestimated so far. The surface characteristics of BGs are key factors in determining the success of any implanted BG-based material in vivo since they regulate the affinity and binding of different biological macromolecules and thereby the interactions between cells and the implant. Therefore, a number of strategies using chemical agents (e.g., glutaraldehyde, silanes) and physical methods (e.g., laser treatment) have been evaluated and applied to design properly, tailor, and improve the surface properties of BGs. All these approaches aim at enhancing the biological activities of BGs, including the induction of cell proliferation and subsequent osteogenesis, as well as the inhibition of bacterial growth and adhesion, thereby reducing infection. In this study, we present an overview of the currently used approaches of surface functionalization and modifications of BGs, along with discussing the biological outputs induced by these changes.

Purpose: Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is the fourth most common cause of cancer-related death in the USA. Local progression, early tumor dissemination and low efficacy of current treatments are the major reasons for its high mortality rate. The ERBB family is over-expressed in PDAC and plays essential roles in its tumorigenesis; however, single-targeted ERBB inhibitors have shown limited activity in this disease. Here, we examined the anti-tumor activity of dacomitinib, a pan-ERBB receptor inhibitor, on PDAC cells., Methods: Anti-proliferative effects of dacomitinib were determined using a cell proliferation assay and crystal violet staining. Annexin V/PI staining, radiation therapy and cell migration and invasion assays were carried out to examine the effects of dacomitinib on apoptosis, radio-sensitivity and cell motility, respectively. Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses were applied to elucidate the molecular mechanisms underlying the anti-tumor activity of dacomitinib., Results: We found that dacomitinib diminished PDAC cell proliferation via inhibition of FOXM1 and its targets Aurora kinase B and cyclin B1. Moreover, we found that dacomitinib induced apoptosis and potentiated radio-sensitivity via inhibition of the anti-apoptotic proteins survivin and MCL1. Treatment with dacomitinib attenuated cell migration and invasion through inhibition of the epithelial-to-mesenchymal transition (EMT) markers ZEB1, Snail and N-cadherin. In contrast, we found that the anti-tumor activity of single-targeted ERBB agents including cetuximab (anti-EGFR mAb), trastuzumab (anti-HER2 mAb), H3.105.5 (anti-HER3 mAb) and erlotinib (EGFR small molecule inhibitor) were marginal., Conclusions: Our findings indicate that dacomitinib-mediated blockade of the ERBB receptors yields advantages over single-targeted ERBB inhibition and provide a rationale for further investigation of the therapeutic potential of dacomitinib in the treatment of ERBB-driven PDAC.

Over the last decade, there has been an impressive growth of new potential applications for bioactive glasses (BGs) in regenerative medicine. Apart from being used in contact with injured bone, BGs are now showing promise in accelerating the healing of soft tissues too, such as epithelium, thus creating new hopes for the repair of damaged skin, gastrointestinal tract and airspaces of the lungs. BGs can form a biological bond with soft tissues, accelerate epithelial cell proliferation, and reduce the inflammation in the injured sites. BGs can also be added to "soft" polymeric matrices for imparting biological extra-functionalities (e.g. enhanced angiogenesis) which play a key role in epithelial reconstruction strategies. The aim of this study is to provide a critical review of the potential of various types of BGs for the repair and regeneration of the epithelial tissues based on the existing data in the literature., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The management of burn injuries is considered an unmet clinical need and, to date, no fully satisfactory solution exists to this problem. This mini-review aims to explore the potential of bioactive glasses (BGs) for burn care due to the therapeutic effects of their ionic dissolution products. BGs have been studied for more than 40 years and boast a long successful history in the substitution of damaged tissues, especially bone. Considering their exceptional versatility and attractive characteristics, these synthetic materials have also recently been proposed in the treatment of soft tissue-related disorders such as skin wounds. Specifically, improving fibroblast proliferation, inducing angiogenesis, and eliciting antibacterial activity (with the additional advantage of avoiding administration of antibiotics) are all considered as key added values carried by BGs in the treatment of burn injuries. However, some issues deserve careful consideration while proceeding with the research, including the selection of suitable BG compositions, appropriate forms of application (e.g., BG fibers, ointments or composite patches), as well as the procedures for reliable in vivo testing.

An event-driven approach based on dynamic optimization and nonlinear model predictive control (NMPC) is investigated together with inline Raman spectroscopy for process monitoring and control. The benefits and challenges in polymerization and morphology monitoring are presented, and an overview of the used mechanistic models and the details of the dynamic optimization and NMPC approach to achieve the relevant process objectives are provided. Finally, the implementation of the approach is discussed, and results from experiments in lab and pilot-plant reactors are presented.

The use of different biomaterials with the ability to accelerate the repair and regeneration processes is of great importance in tissue engineering strategies. On this point, cerium oxide nanoparticles (CNPs or nanoceria) have recently attracted much attention due to their excellent biological properties including anti-oxidant, anti-inflammation and antibacterial activities as well as high angiogenic potential. The results of incorporation of these nano-sized particles into various constructs and scaffolds designed for tissue engineering applications have proven the success of this strategy in terms of improving healing process of different tissues. In this review, we first summarize the physicochemical and biological properties of nanoceria in brief and then present its usability in tissue engineering strategies based on the currently available published reports.

The control of bacterial infections is of particular importance in the field of tissue engineering. Recently, much attention has been addressed toward the use of mesoporous bioactive glasses (MBGs) for antibacterial strategies, primarily because of their capability of acting as carriers for the local release of antimicrobial agents. The incorporation of antibacterial metallic ions including silver (Ag + ), zinc (Zn 2+ ), copper (Cu + and Cu 2+ ), cerium (Ce 3+ and Ce 4+ ), and gallium (Ga 3+ ) cations into the MBG structure and their controlled release is proposed as one of the most attractive strategies for inhibiting bacterial growth and reproduction. Moreover, the possibility of loading and delivering various antibacterial biomolecules (e.g., antibiotics) through the porous structure of MBGs makes them as ideal candidates for antibacterial applications. In this review, we aim to present a comprehensive evaluation of MBG potential regarding antibacterial activities. For this purpose, different types of antibacterial ion-doped and drug-loaded MBGs are introduced and discussed in the light of existing knowledge, along with the significant challenges ahead. STATEMENT OF SIGNIFICANCE: Prevention and treatment of infections is one of the today's greatest challenges in medical sciences, also considering the well-known issues related to increased bacterial resistance to antibiotics. The advent of mesoporous glasses led to the birth of a new class of multifunctional biomaterials acting as bioactive platforms for the local release of organic or inorganic agents eliciting an antimicrobial effect. This reviews summarizes the state of the art of MBGs in this field, highlighting the latest evolutions and the specific role played by metallic antimicrobial ions that can be incorporated in the glass composition and then properly released. Perspective for tissue engineering applications are also discussed to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Over the past decade, the extended research on bioactive glasses (BGs) has drastically grown because of their bioactive nature and unique ability to deliver therapeutics in tissue engineering, regenerative medicine and even cancer research. These strategies mostly rely on the inherent potential of BGs regarding bonding to the living tissues and accelerating the healing process. All the possibilities are strongly associated with releasing various therapeutic ions from the BG structures into the biological environment. Additionally, some types of glasses [i.e., mesoporous bioactive glasses (MBGs)] can serve as suitable platforms for the delivery of various small molecules and pharmaceutical agents. This class of biomaterials is recognised as a highly versatile delivery system, playing a crucial part in the future of medicine., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Epithelial ovarian cancer (EOC) has exhibited marginal improvement in survival rate, despite advances in surgical debulking and chemotherapy regimens. Although the majority of EOC patients achieve a clinical remission after induction therapy, over 80% relapse and succumb to chemoresistant disease. In this regard, it is of paramount importance to elucidate molecular mechanisms and signaling pathways which promote therapy resistance in EOC in order to devise novel and more effective treatment strategies. In this study, we showed that activation of nuclear factor-κB (NF-κB) is significantly higher in therapy-resistant EOC cells compared to chemosensitive counterparts, which was positively associated with resistance to cisplatin, carboplatin, paclitaxel and erlotinib. Bay 11-7082, a highly selective NF-κB inhibitor, reduced cell proliferation, clonogenicity and anoikis resistance in the therapy-resistant EOC cells and induced apoptotic cell death. Moreover, Bay 11-7082 decreased the expression of pro-survival, inflammatory and metastatic genes and synergistically increased anti-proliferative efficacy of cisplatin, carboplatin, paclitaxel and erlotinib. Altogether, these findings suggest that NF-κB is an attractive therapeutic target in EOC to be exploited in translational oncology and Bay 11-7082 is a potential anti-cancer drug to overcome chemoresistance and inhibit proliferation of the EOC cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The biggest strategic challenge for tissue engineering is the development of efficient vascularized networks in engineered tissues and organs. Bioactive glasses (BGs) are potent biomaterials for inducing angiogenesis in hard and soft tissue engineering applications. Because tissue-healing processes strongly depend on angiogenesis, recent interest in BGs has increased dramatically. BGs with improved angiogenetic properties can be developed by adding a range of metallic ions (e.g., Cu 2+ , Co 2+ ) into their structure, but further development of BGs with improved angiogenic activity is required, and many crucial questions remain to be answered. We introduce here the salient features, the hurdles that must be overcome, and the hopes and constraints for the development of this approach., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bioactive glasses caused a revolution in healthcare and paved the way for modern biomaterial-driven regenerative medicine. The first 45S5 glass composition, invented by Larry Hench fifty years ago, was able to bond to living bone and to stimulate osteogenesis through the release of biologically-active ions. 45S5-based glass products have been successfully implanted in millions of patients worldwide, mainly to repair bone and dental defects and, over the years, many other bioactive glass compositions have been proposed for innovative biomedical applications, such as soft tissue repair and drug delivery. The full potential of bioactive glasses seems still yet to be fulfilled, and many of today's achievements were unthinkable when research began. As a result, the research involving bioactive glasses is highly stimulating and requires a cross-disciplinary collaboration among glass chemists, bioengineers, and clinicians. The present article provides a picture of the current clinical applications of bioactive glasses, and depicts six relevant challenges deserving to be tackled in the near future. We hope that this work can be useful to both early-stage researchers, who are moving with their first steps in the world of bioactive glasses, and experienced scientists, to stimulate discussion about future research and discover new applications for glass in medicine., Competing Interests: The authors declare no conflict of interest.

Bone regeneration is considered as an unmet clinical need, the aim of this study is to investigate the osteogenic potential of three different mesenchymal stem cells (MSCs) derived from human bone marrow (BM-MSCs), umbilical cord Wharton's jelly (UC-MSCs), and adipose (AD-MSCs) seeded on a recently developed nanocomposite scaffold (bioactive glass/gelatin) implanted in rat animal models with critical size calvarial defects. In this study, after isolation, culture, and characterization, the MSCs were expanded and seeded on the scaffolds for in vitro and in vivo studies. The adhesion, proliferation, and viability of the cells on the scaffolds evaluated in vitro, showed that the scaffolds were biocompatible for further examinations. In order to evaluate the scaffolds in vivo, rat animal models with critical size calvarial defects were randomly categorized in four groups and treated with the scaffolds. The animals were sacrificed at the time points of 4 and 12 weeks of post-implantation, bone healing process were investigated. The histological and immunohistological observations showed (p < 0.01) higher osteogenesis capacity in the group treated with BM-MSCs/scaffolds compared to the other groups. However, the formation of new angiogenesis was evidently higher in the defects filled with UC-MSCs/scaffolds. This preliminary study provides promising data for further clinical trials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 61-72, 2018., (© 2016 Wiley Periodicals, Inc.)

Repair and regeneration of disorders affecting cardiac and pulmonary tissues through tissue-engineering-based approaches is currently of particular interest. On this matter, different families of bioactive glasses (BGs) have recently been given much consideration with respect to treating refractory diseases of these tissues, such as myocardial infarction. The inherent properties of BGs, including their ability to bond to hard and soft tissues, to stimulate angiogenesis, and to elicit antimicrobial effects, along with their excellent biocompatibility, support these newly proposed strategies. Moreover, BGs can also act as a bioactive reinforcing phase to finely tune the mechanical properties of polymer-based constructs used to repair the damaged cardiac and pulmonary tissues. In the present study, we evaluated the potential of different forms of BGs, alone or in combination with other materials (e.g., polymers), in regards to repair and regenerate injured tissues of cardiac and pulmonary systems., Competing Interests: The authors declare no conflict of interest.

Designing and developing new biomaterials to accelerate bone healing are currently under progress. In this study, we attempted to promote osteogenesis using strontium- and cobalt-substituted bioactive glasses (BGs) seeded with human umbilical cord perivascular cells (HUCPVCs) in a critical size defect in the distal femur of rabbit animal model. The BG particles were successfully synthesized in the form of granules using the melt-derived route. After being isolated, HUCPVCs were expanded and then characterized to use during in vitro and in vivo procedures. The in vitro effects of the synthesized glasses on the isolated HUCPVCs as well as on cell lines SaOS-2 (selected for screening the osteogenetic potential) and HUVEC (selected for screening the angiogenic potential) were assessed by analyzing cytotoxicity, cell attachment, bone-like nodule formation, and real time PCR. The results of in vitro tests indicated cytocompatibility of the synthesized BG particles. For in vivo study, the HUCPVCs-seeded BGs were implanted into the animal's body. Radiographic imaging, histology and immunohistology staining were performed on the harvested specimens at 4 and 12weeks post-surgery. The in vivo evaluation of the samples showed that all the cell/glass constructs accelerated bone healing process in comparison with blank controls. The best in vitro and in vivo results were associated to the BGs containing both strontium and cobalt ions. This group of bioactive glasses is able to promote both osteogenesis and angiogenesis and can therefore be highly suitable for the development of advanced functional bone substitutes., Statement of Significance: Bone regeneration is considered as an unmet clinical need. The most recent researches focused on incorporation of strontium (Sr 2+ ) and cobalt (Co 2+ ) ions into bioactive glasses structure. Strontium is an alkaline earth metal which is currently used in the treatment of osteoporosis. Also, cobalt is considered as another promising element in the bone regeneration field that may induce hypoxia-mediated angiogenesis. In this study, the osteogenic potential of the strontium- and cobalt-substituted bioactive glasses in granule form seeded with human umbilical cord perivascular cells (HUCPVCs) was evaluated in vitro and in vivo. Indeed, the main goal of this study was to improve the osteogenenic and angiogenic properties of bioactive glasses through the incorporation of strontium and cobalt ions in the glass composition. Although some researches have been conducted on this subject, the influence of the simultaneous use of strontium and cobalt ions on the improvement of bone healing in vivo has been not yet well understood and, therefore, deserves further investigation., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this research, the osteoinduction effect of a novel variant of bone morphogenetic protein-7 (BMP-7), delivered through bone marrow mesenchymal stem cells (BM-MSCs) seeded on bioactive glass/gelatin nanocomposite scaffolds, was evaluated in a calvarial critical size defect in rats. After being harvested and characterized in vitro, BM-MSCs were infected by a plasmid vector containing BMP-7 encoding gene enriched with a heparin-binding site (B2BMP-7) to assess its osteogenic effects in vivo. The animals were randomly categorized into three groups receiving the scaffold alone (group I), the scaffold seeded with BM-MSCs (group II), and the scaffold seeded with manipulated BM-MSCs (group III). After 2, 4 and 12 postoperative weeks, the animals were sacrificed and the harvested specimens were analyzed using histological and immunohistochemical staining. The results of in vitro tests (preliminary screening) showed that the synthesized scaffolds were biocompatible constructs supporting cell attachment and expansion. The in vivo results revealed higher osteogenesis in the defects filled with the B2BMP-7 excreting BM-MSCs/scaffolds compared to the other two groups. After 12weeks of implantation, fully mature newly formed bone was detected throughout the damaged site, which indicates a synergistic effect of cells, scaffolds and growth factors in the process of tissue regeneration. Therefore, bioactive glass-containing scaffolds pre-seeded with manipulated BM-MSCs exhibit an effective combination to improve osteogenesis in bone defects, and the approach followed in this work could have a significant impact in the development of novel tissue engineering constructs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In a recent publication, Nakamura and co-workers studied the termination mechanism in the radical polymerization of acrylates. Contrary to conventional thinking, their conclusion is that termination is overwhelmingly by disproportionation. This finding impacts on a large body of the previous work in the polymerization of acrylic monomers which this work seeks to address. Analysis of the molecular weight distribution of acrylic polymers obtained under different polymerization conditions shows that termination by combination is the more probable mechanism for mutual termination of secondary radicals. It is proposed that in the experiments conducted by Nakamura and co-workers, backbiting plays a key role and their experimental data are reinterpreted, showing that they are more revealing with respect to the mode of termination of the midchain radical produced by backbiting, than to bimolecular termination of secondary radicals., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background/purpose: Tuberculosis (TB) is a crucial health problem. Prevention of the disease requires rapid diagnosis. Rapid liquid culture systems, nucleic acid amplification tests, and high-performance liquid chromatography (HPLC) are among the rapid tests used for detecting Mycobacterium species. However, these tests are expensive and require extensive equipment and expertise, which is hardly affordable in resource-poor countries. Although direct microscopy is performed routinely as an initial step for detection of the bacteria, it is not sufficiently sensitive. As a result, we thought of establishing a low-cost immunological test that can potentially replace direct microscopy with higher sensitivity and specificity., Methods: The assay is based on pre-incubation of biotinylated rabbit antibody against Antigen 60 (A60) with a solution containing Bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis (MTB) followed by incubation with a streptavidin-alkaline phosphatase (STA-ALP) conjugate. The test is devised in enzyme-linked immunosorbent assay (ELISA) and non-ELISA formats, therefore it does not require extensive facilities and expertise., Results: The ELISA format showed a 100-fold improvement in the lower detection limit of BCG compared with direct microscopy. With the non-ELISA formats, there was a 2- and 16-fold improvement for the cartridge assay and the microfuge tube assay, respectively., Conclusion: In conclusion, we successfully detected BCG and MTB in solution using the new immunological method. Our results are very promising and the new immunological method could potentially replace direct microscopy with higher sensitivity and specificity., (Copyright © 2014. Published by Elsevier B.V.)

Background: Detection of hepatitis C virus specific antibodies is the initial step in chronic HCV diagnosis. HCV NS4B is among the most immunogenic HCV antigens and has been widely used in commercial Enzyme Immunoassays (EIA). Additionally, NS4B, a key protein in the virus replication, can be an alternative target for antiviral therapy., Objectives: Development of a new method for high-level expression and purification of NS4B coding region was the aim of the report., Materials and Methods: Viral RNA was purified from the serum of an HCV positive patient and NS4B coding region was amplified using nested RT-PCR. PCR products were cloned into pET102/D-TOPO expression vector and transformed into E. coli BL21. Induction was performed by adding 1 mM isopropyl-β-D-thiogalactopyranoside (IPTG) to the culture medium. Immunoreactivity of the purified recombinant proteins was evaluated by immunoblotting and indirect enzymelinked immunosorbent assay (ELISA)., Results: The recombinant NS4B protein was expressed and its immunoreactivity was confirmed by ELISA and western blotting., Conclusions: The directional TOPO cloning provides an efficient and easy platform for heterologous expression of immunoreactive HCV NS4B.

Despite the studies so far about the non-specific binding of antibody molecule to the plastic of solid phase in enzyme-linked immunoassays, background binding in microwell Elisa continues to be a troublesome problem.Non-specific immunoglobulin from an undiluted serum sample can adhere to the surface of a 'blocked' plate to result in a maximal signal in an antigen capture assay for specific antibody to render analysis virtually impossible in undiluted serum when using labelled anti-species antibodies. Yet it is desirable in many circumstances that the maximum sensitivity achievable by the simple expedient of using a concentrated sample (undiluted serum) be exploited, for example in the analysis of antibodies to HIV in the interest of earlier diagnosis. To circumvent this problem we have developed an alternative strategy in which a biotinylated capture reagent is preincubated with the serum sample for the necessary time after which the biotinylated ligand/antibody complex is itself rapidly captured in streptavidin-coated wells at 4°C, with subsequent detection with labelled anti-species immunoglobulin. This manoeuvre enables the capture ligand to be incubated with undiluted serum sample for long time periods resulting in improved specificity of detection. By this means we describe a general method to improve the specificity of serum antibody immunoassays which will be expected to produce the benefit of more rapid diagnosis by signalling antibody production earlier in the abnormal state. Furthermore, our new method could be used to reduce non-specific binding in other immunological assays such as antibody arrays to which much attention has recently been paid.

Background: Candida species are among the most common causes of opportunistic fungal diseases. Among Candida species, Candida albicans is responsible for most infections. Having many strains, C. albicans is very polymorph. C. dubliniensis is very similar to albicans species both morphologically and physiologically. For an infection to occur, cell wall proteins play an important role as they enable yeast to adhere to host cells and begin pathogenesis. Therefore, we decided to extract these proteins and examine them through common molecular methods of protein analysis including SDS-PAGE., Methods: Initially cell wall proteins of two C. albicans strains (CBS 562 and PTCC6027) and one C. dubliniensis strain (CBS7987) were extracted by using a solution of beta-mercaptoethanol and ammonium carbonate. After dialysis against Tris-HCL buffer, SDS gel electrophoresis was performed on the proteins extract. Bands were then visualized by using three different staining methods among which one method provided improved detection., Results: By using Coomassie Brilliant Blue staining method, proteins with molecular weight of 42, 66.2 and 200 kDa were detected. By using Silver staining method, proteins with molecular weight of 21.5, 28.5 and 37 kDa were detected. However, using combined Coomassie Brilliant Blue & Sliver staining method visualized more bands resulting in improved detection., Conclusion: To answer many existing questions about fungal diseases, fungi cell wall proteins are necessary to be examined. To commence such examinations, a simple step may be an SDS-PAGE performance on as many strains as possible. A combined staining method can enhance bands detection.

Proteins constitute a group of key molecules with many applications in tissue engineering. Use of proteins provided from natural sources has several limitations which are overcome by the use of recombinant proteins. So far, the recombinant forms of many proteins with tissue engineering applications have been developed including structural proteins, growth factors and cytokines. This technology has enabled the development of specifically designed proteins such as growth factors with matrix binding domains, and hybrid structural proteins with improved mechanical properties. Recombinant proteins are produced either ex vivo or in vivo, by local gene therapy protocols, and are of medical and economic benefits. Due to the high applicability of recombinant proteins in tissue engineering, it is recommended to include this platform as an infrastructural element in any tissue engineering program.