Synthesis, surface modifications, and biomedical applications of carbon nanofibers: Electrospun vs vapor-grown carbon nanofibers.

Engineered nanostructures are materials with promising properties, enabled by precise design and fabrication, as well as size-dependent effects. Biomedical applications of nanomaterials in disease-specific prevention, diagnosis, treatment, and recovery monitoring require precise, specific, and sophisticated approaches to yield effective and long-lasting favorable outcomes for patients. In this regard, carbon nanofibers (CNFs) have been indentified due to their interesting properties, such as good mechanical strength, high electrical conductivity, and desirable morphological features. Broadly speaking, CNFs can be categorized as vapor-grown carbon nanofibers (VGCNFs) and carbonized CNFs (e.g., electrospun CNFs), which have distinct microstructure, morphologies, and physicochemical properties. In addition to their physicochemical properties, VGCNFs and electrospun CNFs have distinct performances in biomedicine and have their own pros and cons. Indeed, several review papers in the literature have summarized and discussed the different types of CNFs and their performances in the industrial, energy, and composites areas. Crucially however, there is room for a comprehensive review paper dealing with CNFs from a biomedical point of view. The present work therefore, explored various types of CNFs, their fabrication and surface modification methods, and their applications in the different branches of biomedical engineering.

Plasmonic hyperthermia or radiofrequency electric field hyperthermia of cancerous cells through green-synthesized curcumin-coated gold nanoparticles.

Nanoparticle-mediated hyperthermia is one of the prominent adjuvant therapies which has been faced by many problematic challenges such as efficiency and safety. To compare the nanoparticle-mediated photothermal therapy and radiofrequency electric field hyperthermia, green-synthesized curcumin-coated gold nanoparticles (Cur@AuNPs) were applied in an in vitro study. Using recently published methodologies, each step of the study was performed. Through green chemistry, curcumin was applied as both a reducing and a capping agent in the gold nanoparticle synthesis process. Various techniques were applied for the characterization of the synthesized nanoparticles. The heating rate of Cur@AuNPs in the presence of RFEF or laser irradiation was recorded by using a non-contact thermometer. The cellular uptake of the Cur@AuNPs was studied by ICP-AES. The cellular viability and apoptosis rate of different treatment were measured to investigate the effect of two different nano-hyperthermia techniques on the murine colorectal cancer cell line. The average size of Cur@AuNPs was 7.2 ± 3.3 nm. The stability of the gold nanoparticles in the phosphate buffer saline with and without fetal bovine serum was verified by UV-Vis spectroscopy. FTIR, UV-Vis spectroscopy, and TEM indicate that the stability is a result of phenolic coating on the surface of nanoparticles. Cur@AuNPs can absorb both light and radiofrequency electric field exposure in a way that could kill cancerous cells in a significant number (30% in 64 µg/ml concentration). Green-synthesized Cur@AuNPs could induce apoptosis cell death in photothermal therapy and radiofrequency electric field hyperthermia.

Evaluation of two fungal exopolysaccharides as potential biomaterials for wound healing applications.

Microbial exopolysaccharides (EPSs) are mostly produced by bacteria and fungi and have potential use in the production of biomedical products such as nutraceuticals and in tissue engineering applications. The present study investigated the in vitro biological activities and in vivo wound healing effects of EPSs produced from a Sclerotium-forming fungus (Sclerotium glucanicum DSM 2159) and a yeast (Rhodosporidium babjevae), denoted as scleroglucan (Scl) and EPS-R, respectively. EPS yields of 0.9 ± 0.07 g/L and 1.11 ± 0.4 g/L were obtained from S. glucanicum and R. babjevae, respectively. The physicochemical properties of the EPSs were characterized using infrared spectroscopy and scanning electron microscopy. Further investigations of the biological properties showed that both EPSs were cytocompatible toward the human fibroblast cell line and demonstrated  hemocompatibility. Favorable wound healing capacities of the EPSs (10 mg/mL) were also established via in vivo tests. The present study therefore showed that the EPSs produced by S. glucanicum and R. babjevae have the potential use as biocompatible components for the promotion of dermal wound healing.

Fabrication and Characterization of Nanocomposite Hydrogel Based on Alginate/Nano-Hydroxyapatite Loaded with Linum usitatissimum Extract as a Bone Tissue Engineering Scaffold.

In the current paper, we fabricated, characterized, and applied nanocomposite hydrogel based on alginate (Alg) and nano-hydroxyapatite (nHA) loaded with phenolic purified extracts from the aerial part of Linum usitatissimum (LOH) as the bone tissue engineering scaffold. nHA was synthesized based on the wet chemical technique/precipitation reaction and incorporated into Alg hydrogel as the filler via physical cross-linking. The characterizations (SEM, DLS, and Zeta potential) revealed that the synthesized nHA possess a plate-like shape with nanometric dimensions. The fabricated nanocomposite has a porous architecture with interconnected pores. The average pore size was in the range of 100-200 µm and the porosity range of 80-90%. The LOH release measurement showed that about 90% of the loaded drug was released within 12 h followed by a sustained release over 48 h. The in vitro assessments showed that the nanocomposite possesses significant antioxidant activity promoting bone regeneration. The hemolysis induction measurement showed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability/proliferation confirmed the biocompatibility of the nanocomposites, which induced proliferative effects in a dose-dependent manner. This study revealed the fabricated nanocomposites are bioactive and osteoactive applicable for bone tissue engineering applications.

Toxicological profile of lipid-based nanostructures: are they considered as completely safe nanocarriers?

Nanoparticles are ubiquitous in the environment and are widely used in medical science (e.g. bioimaging, diagnosis, and drug therapy delivery). Due to unique physicochemical properties, they are able to cross many barriers, which is not possible for traditional drugs. Nevertheless, exposure to NPs and their following interactions with organelles and macromolecules can result in negative effects on cells, especially, they can induce cytotoxicity, epigenicity, genotoxicity, and cell death. Lipid-based nanomaterials (LNPs) are one of the most important achievements in drug delivery mainly due to their superior physicochemical and biological characteristics, particularly its safety. Although they are considered as the completely safe nanocarriers in biomedicine, the lipid composition, the surfactant, emulsifier, and stabilizer used in the LNP preparation, and surface electrical charge are important factors that might influence the toxicity of LNPs. According to the author's opinion, their toxicity profile should be evaluated case-by-case regarding the intended applications. Since there is a lack of all-inclusive review on the various aspects of LNPs with an emphasis on toxicological profiles including cyto-genotoxiciy, this comprehensive and critical review is outlined.

A novel multi-stimuli-responsive theranostic nanomedicine based on Fe3O4@Au nanoparticles against cancer.

A novel multi-stimuli-responsive theranostic nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly(N-isopropylacrylamide-block-acrylic acid) (HS-PNIPAAm-b-PAA) onto Fe3O4@Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, Fe3O4@Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm-b-PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized Fe3O4@Au NPs by Au-S bonding. The Dox loading capacity of the synthesized Fe3O4@Au/Polymer theranostic NPs was calculated to be 81%. The theranostic nanomedicine exhibited excellent in vitro drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated Fe3O4@Au/Polymer has high potential as theranostic nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and Fe3O4 nanomaterials in its structure.

Sciatic nerve regeneration by using collagen type I hydrogel containing naringin.

In the present study, collagen hydrogel containing naringin was fabricated, characterized and used as the scaffold for peripheral nerve damage treatment. The collagen was dissolved in acetic acid, naringin added to the collagen solution, and cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide powder (EDC; 0.10 mM) to form the hydrogel. The microstructure, swelling behavior, biodegradation, and cyto/hemocompatibility of the fabricated hydrogels were assessed. Finally, the healing efficacy of the prepared collagen hydrogel loaded with naringin on the sciatic nerve crush injury was assessed in the animal model. The characterization results showed that the fabricated hydrogels have a porous structure containing interconnected pores with the average pore size of 90 µm. The degradation results demonstrated that about 70% of the primary weight of the naringin loaded hydrogel had been lost after 4 weeks of storage in PBS. The in vitro study showed that the proliferation of Schwann cells on the collagen/naringin hydrogel was higher than the control group (tissue culture plate) at both 48 and 72 h after cell seeding and even significantly higher than pure collagen 72 h after cell seeding (*p < 0.005, **p < 0.001). The animal study implied that the sciatic functional index reached to -22.13 ± 3.00 at the end of 60th days post-implantation which was statistically significant (p < 0.05) compared with the negative control (injury without the treatment) (-82.60 ± 1.06), and the pure collagen hydrogel (-59.80 ± 3.20) groups. The hot plate latency test, the compound muscle action potential, and wet weight-loss of the gastrocnemius muscle evaluation confirmed the positive effect of the prepared hydrogels on the healing process of the induced nerve injury. In the final, the histopathologic examinations depicted that the collagen/naringin hydrogel group reduced all the histological changes induced from the nerve injury and showed more resemblance to the normal sciatic nerve, with well-arranged fibers and intact myelin sheath. The overall results implied that the prepared collagen/naringin hydrogel can be utilized as a sophisticated alternative to healing peripheral nerve damages.

A Systematic Review of the Genotoxicity and Antigenotoxicity of Biologically Synthesized Metallic Nanomaterials: Are Green Nanoparticles Safe Enough for Clinical Marketing?

Background and objectives: Although studies have elucidated the significant biomedical potential of biogenic metallic nanoparticles (MNPs), it is very important to explore the hazards associated with the use of biogenic MNPs. Evidence indicates that genetic toxicity causes mutation, carcinogenesis, and cell death. Materials and Methods: Therefore, we systematically review original studies that investigated the genotoxic effect of biologically synthesized MNPs via in vitro and in vivo models. Articles were systematically collected by screening the literature published online in the following databases; Cochrane, Web of Science, PubMed, Scopus, Science Direct, ProQuest, and EBSCO. Results: Most of the studies were carried out on the MCF-7 cancer cell line and phytosynthesis was the general approach to MNP preparation in all studies. Fungi were the second most predominant resource applied for MNP synthesis. A total of 80.57% of the studies synthesized biogenic MNPs with sizes below 50 nm. The genotoxicity of Ag, Au, ZnO, TiO2, Se, Cu, Pt, Zn, Ag-Au, CdS, Fe3O4, Tb2O3, and Si-Ag NPs was evaluated. AgNPs, prepared in 68.79% of studies, and AuNPs, prepared in 12.76%, were the two most predominant biogenic MNPs synthesized and evaluated in the included articles. Conclusions: Although several studies reported the antigenotoxic influence of biogenic MNPs, most of them reported biogenic MNP genotoxicity at specific concentrations and with a dose or time dependence. To the best of our knowledge, this is the first study to systematically evaluate the genotoxicity of biologically synthesized MNPs and provide a valuable summary of genotoxicity data. In conclusion, our study implied that the genotoxicity of biologically synthesized MNPs varies case-by-case and highly dependent on the synthesis parameters, biological source, applied assay, etc. The gathered data are required for the translation of these nanoproducts from research laboratories to the clinical market.

Physical, dosimetric and clinical aspects and delivery systems in neutron capture therapy.

Neutron capture therapy (NCT) is a targeted radiotherapy for cancer treatment. In this method, neutrons with a spectra/specific energy (depending on the type of agent used for NCT) are captured with an agent that has a high cross-section with these neutrons. There are some agents that have been proposed in NCT including 10B, 157Gd and 33S. Among these agents, only 10B is used in clinical trials. Application of 157Gd is limited to in-vivo and in-vitro research. In addition, 33S has been applied in the field of Monte Carlo simulation. In BNCT, the only two delivery agents which are presently applied in clinical trials are BPA and BSH, but other delivery systems are being developed for more effective treatment in NCT. Neutron sources used in NCT are fission reactors, accelerators, and 252Cf. Among these, fission reactors have the most application in NCT. So far, BNCT has been applied to treat various cancers including glioblastoma multiforme, malignant glioma, malignant meningioma, liver, head and neck, lung, colon, melanoma, thyroid, hepatic, gastrointestinal cancer, and extra-mammary Paget's disease. This paper aims to review physical, dosimetric and clinical aspects as well as delivery systems in NCT for various agents.

Multifunctional plant virus nanoparticles: An emerging strategy for therapy of cancer.

Cancer therapy requires sophisticated treatment strategies to obtain the highest success. Nanotechnology is enabling, revolutionizing, and multidisciplinary concepts to improve conventional cancer treatment modalities. Nanomaterials have a central role in this scenario, explaining why various nanomaterials are currently being developed for cancer therapy. Viral nanoparticles (VNPs) have shown promising performance in cancer therapy due to their unique features. VNPs possess morphological homogeneity, ease of functionalization, biocompatibility, biodegradability, water solubility, and high absorption efficiency that are beneficial for cancer therapy applications. In the current review paper, we highlight state-of-the-art properties and potentials of plant viruses, strategies for multifunctional plant VNPs formulations, potential applications and challenges in VNPs-based cancer therapy, and finally practical solutions to bring potential cancer therapy one step closer to real applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Surface modification of polycaprolactone nanofibers through hydrolysis and aminolysis: a comparative study on structural characteristics, mechanical properties, and cellular performance.

Hydrolysis and aminolysis are two main commonly used chemical methods for surface modification of hydrophobic tissue engineering scaffolds. The type of chemical reagents along with the concentration and treatment time are main factors that determine the effects of these methods on biomaterials. In the present study, electrospun poly (ℇ-caprolactone) (PCL) nanofibers were modified through hydrolysis and aminolysis. The applied chemical solutions for hydrolysis and aminolysis were NaOH (0.5-2 M) and hexamethylenediamine/isopropanol (HMD/IPA, 0.5-2 M) correspondingly. Three distinct incubation time points were predetermined for the hydrolysis and aminolysis treatments. According to the scanning electron microscopy results, morphological changes emerged only in the higher concentrations of hydrolysis solution (1 M and 2 M) and prolonged treatment duration (6 and 12 h). In contrast, aminolysis treatments induced slight changes in the morphological features of the electrospun PCL nanofibers. Even though surface hydrophilicity of PCL nanofibers was noticeably improved through the both methods, the resultant influence of hydrolysis was comparatively more considerable. As a general trend, both hydrolysis and aminolysis resulted in a moderate decline in the mechanical performance of PCL samples. Energy dispersive spectroscopy analysis indicated elemental changes after the hydrolysis and aminolysis treatments. However, X-ray diffraction, thermogravimetric analysis, and infrared spectroscopy results did not show noticeable alterations subsequent to the treatments. The fibroblast cells were well spread and exhibited a spindle-like shape on the both treated groups. Furthermore, according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the surface treatment procedures ameliorated proliferative properties of PCL nanofibers. These findings represented that the modified PCL nanofibrous samples by hydrolysis and aminolysis treatments can be considered as the potentially favorable candidates for tissue engineering applications.

Fabrication, characterization and biological properties evaluation of bioactive scaffold based on mineralized carbon nanofibers.

Tissue engineering as an innovative approach aims to combine engineering, biomaterials and biomedicine to eliminate the drawbacks of conventional bone defect treatment. In the current study, we fabricated bioengineered electroactive and bioactive mineralized carbon nanofibers as the scaffold for bone tissue engineering applications. The scaffold was fabricated using the sol-gel method and thoroughly characterized by SEM imaging, EDX analysis and a 4-point probe. The results showed that the CNFs have a diameter of 200 ± 19 nm and electrical conductivity of 1.02 ± 0.12 S cm-1. The in vitro studies revealed that the synthesized CNFs were osteoactive and supported the mineral crystal deposition. The hemolysis study confirmed the hemocompatibility of the CNFs and cell viability/proliferation sassy using an MTT assay kit showed the proliferative activities of mineralized CNFs. In conclusion, this study revealed that the mineralized CNFs synthesized by the combination of sol-gel and electrospinning techniques were electroactive, osteoactive and biocompatible, which can be considered an effective bone tissue engineering scaffold.Communicated by Ramaswamy H. Sarma.

Composites based on alginate containing formylphosphazene-crosslinked chitosan and its Cu(II) complex as an antibiotic-free antibacterial hydrogel dressing with enhanced cytocompatibility.

Hydrogels based on chitosan or alginate biopolymers are believed to be desirable for covering skin lesions. In this research, we explored the potential of a new composite hydrogels series of sodium alginate (Alg) filled with cross-linked chitosan to use as hydrogel wound dressings. Cross-linked chitosan (CSPN) was synthesized by Schiff-base reaction with aldehydated cyclophosphazene, and its Cu(II) complex was manufactured and identified. Then, their powder suspension and Alg were transformed into hydrogel via ion-crosslinking with Ca2+. The hydrogel constituents were investigated by using FTIR, XRD, rheological techniques, and thermal analysis including TGA (DTG) and DSC. Moreover, structure optimization calculations were performed with the Material Studio 2017 program based on DFT-D per Dmol3 module. Examination of Alg's interactions with CSPN and CSPN-Cu using this module demonstrated that Alg molecules can be well adsorbed to the particle's surface. By changing the dosage of CSPN and CSPN-Cu, the number and size of pores, swelling rate, degradation behavior, protein absorption rate, cytotoxicity and blood compatibility were changed significantly. Subsequently, we employed erythromycin as a model drug to assess the entrapment efficiency, loading capacity, and drug release rate. FITC staining was selected to verify the hydrogels' intracellular uptake. Assuring the cytocompatibility of Alg-based hydrogels was approved by assessing the survival rate of fibroblast cells using MTT assay. However, the presence of Cu(II) in the developed hydrogels caused a significant antibacterial effect, which was comparable to the antibiotic-containing hydrogels. Our findings predict these porous, biodegradable, and mechanically stable hydrogels potentially have a promising future in the wound healing as antibiotic-free antibacterial dressings.

Curcumin-loaded porous particles functionalized with pH-responsive cell-penetrating peptide for colorectal cancer targeted drug delivery.

The anticancer properties of curcumin have been broadly examined in several shapes, such as nanoparticles and nanocomposite structures. Despite its benefits, curcumin also has some disadvantages, including rapid metabolism, poor absorption, and rapid systemic excretion. Therefore, numerous strategies have been used to increase curcumin's bioavailability. One of these approaches is the use of porous particles like aerogels as drug carriers. Aerogels are special due to their peculiar physical structure. They have a high specific surface area, a significant amount of porosity, and a solid composition, which make them a good choice for drug delivery systems. In the present study, a pH-sensitive aerogel was constructed and evaluated for targeted drug delivery of curcumin to colon cancer. To control the release of curcumin, trehalose was used as a coating agent, and PLP (poly(l-lysine isophthalamide)) was used as a targeted drug delivery agent. PLP is a pseudo-peptidic polymer that increases the cell permeability. In order to investigate and compare the synthesized aerogel before and after loading curcumin and coating with trehalose, physicochemical characterization analyses were performed. Finally, the efficacy of the final formulation was evaluated on HT29 colon cells using the cell bioavailability test. The results indicated the successful synthesis of the aerogel with porous structure with solitary cavities. The trehalose coating performed well, preventing drug release at lower pH but allowing the drug to be released at its intended site. The designed curcumin-loaded porous particles functionalized with PLP showed significant efficacy due to increasing penetration of curcumin into cells, and has potential for use as a new drug carrier with dual effectivity in cancer therapy.

Targeted protein modification as a paradigm shift in drug discovery.

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases.

Fabrication and characterization of Persian gum-based hydrogel loaded with gentamicin-loaded natural zeolite: An in vitro and in silico study.

The main purpose of this study is to synthesize and characterize Persian gum-based hydrogel composited with gentamicin (Gen)-loaded natural zeolite (Clinoptilolite) and to evaluate its biological properties. Clinoptilolite (CLN) was decorated with Gen, and the conjugation was confirmed using computational and experimental assessments. The Monte Carlo adsorption locator module was used to reveal the physicochemical nature of the adsorption processes of Gen on CLN and ALG and gum on Gen@ CLN in Materials Studio 2017 software. Based on the high negative results, the adsorption process was found to be endothermic in all studied cases, and the interaction energies were in the range of physisorption for Gen on CLN and ALG and gum on Gen@CLN. Dynamic light scattering (DLS) and zeta potential analysis showed that the size of pristine CLN was around 2959 nm and the conjugation decreased the size significantly to approximately 932 nm. The hydrogel characterizations showed that the Gen-decorated CLNs are homogenously dispersed into the hydrogel matrix, and the resultant hydrogels have a porous structure with interconnected pores. The release kinetics evaluation showed that around 80 % of Gen was released from the nanocomposite drug during the first 10 h. In vitro studies revealed hemocompatibility and cytocompatibility of the nanocomposite. Microbial assessments indicated dose-dependent antibacterial activity of the hydrogel against gram (+) and gram (-) bacteria. The results showed that the fabricated hydrogel nanocomposite exhibits favorable physicochemical and biological properties.

Critical parameters to translate gold nanoparticles as radiosensitizing agents into the clinic.

Radiotherapy is an inevitable choice for cancer treatment that is applied as combinatorial therapy along with surgery and chemotherapy. Nevertheless, radiotherapy at high doses kills normal and tumor cells at the same time. In addition, some tumor cells are resistant to radiotherapy. Recently, many researchers have focused on high-Z nanomaterials as radiosensitizers for radiotherapy. Among them, gold nanoparticles (GNPs) have shown remarkable potential due to their promising physical, chemical, and biological properties. Although few clinical trial studies have been performed on drug delivery and photosensitization with lasers, GNPs have not yet received Food and Drug Administration approval for use in radiotherapy. The sensitization effects of GNPs are dependent on their concentration in cells and x-ray energy deposition during radiotherapy. Notably, some limitations related to the properties of the GNPs, including their size, shape, surface charge, and ligands, and the radiation source energy should be resolved. At the first, this review focuses on some of the challenges of using GNPs as radiosensitizers and some biases among in vitro/in vivo, Monte Carlo, and clinical studies. Then, we discuss the challenges in the clinical translation of GNPs as radiosensitizers for radiotherapy and proposes feasible solutions. And finally, we suggest that certain areas be considered in future research. This article is categorized under: Therapeutic Approaches and Drug Discovery > NA.

Exopolysaccharide from the yeast Papiliotrema terrestris PT22AV for skin wound healing.

INTRODUCTION: Exopolysaccharides (EPSs) are high-value functional biomaterials mainly produced by bacteria and fungi, with nutraceutical, therapeutic and industrial potentials. OBJECTIVES: This study sought to characterize and assess the biological properties of the EPS produced by the yeast Papiliotrema terrestris PT22AV. METHODS: After extracting the yeast's DNA and its molecular identification, the EPS from P. terrestris PT22AV strain was extracted and its physicochemical properties (structural, morphological, monosaccharide composition and molecular weight) were characterized. The EPS's in vitro biological activities and in vivo wound healing potential were also evaluated. RESULTS: The obtained EPS was water-soluble and revealed an average molecular weight (Mw) of 202 kDa. Mannose and glucose with 97% and 3% molar percentages, respectively, constituted the EPS. In vitro antibacterial activity analysis of the extracted EPS exhibited antibacterial activity (>80%) against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis at a concentration of 2 mg/mL. The EPS showed cytocompatibility against the human fibroblast and macrophage cell lines and the animal studies showed a dose-dependent wound healing capacity of the EPS with higher wound closure at 10 mg/mL compared to negative and positive control after 14 days. CONCLUSION: The EPS from P. terrestris PT22AV could serve as a promising source of biocompatible macromolecules with potential for skin wound healing.

Hydrogel nanocomposite based on alginate/zeolite for burn wound healing: In vitro and in vivo study.

Objectives: The main objective of the current assay was to evaluate the antibacterial and regenerative effects of hydrogel nanocomposite containing pure natural zeolite (clinoptilolite) integrated with alginate (Alg) as wound healing/dressing biomaterials. Materials and Methods: The zeolites were size excluded, characterized by SEM, DLS, XRD, FTIR, and XRF, and then integrated into Alg hydrogel followed by calcium chloride crosslinking. The Alg and alginate zeolite (Alg/Zeo) hydrogel was characterized by swelling and weight loss tests, also the antibacterial, hemocompatibility, and cell viability tests were performed. In animal studies, the burn wound was induced on the back of rats and treated with the following groups: control, Alg hydrogel, and Alg/Zeo hydrogel. Results: The results showed that the hydrodynamic diameter of zeolites was 367 ± 0.2 nm. Zeolites did not show any significant antibacterial effect, however, the hydrogel nanocomposite containing zeolite had proper swelling as well as hemocompatibility and no cytotoxicity was observed. Following the creation of a third-degree burn wound on the back of rats, the results indicated that the Alg hydrogel and Alg/Zeo nanocomposite accelerated the wound healing process compared with the control group. Re-epithelialization, granulation tissue thickness, collagenization, inflammatory cell recruitment, and angiogenesis level were not significantly different between Alg and Alg/Zeo nanocomposite. Conclusion: These findings revealed that although the incorporation of zeolites did not induce a significant beneficial effect in comparison with Alg hydrogel, using zeolite capacity in hydrogel for loading the antibiotics or other effective compounds can be considered a promising wound dressing.

Multifunctional nanostructures: Intelligent design to overcome biological barriers.

Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and pharmacokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is intimately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.