Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. In vivo experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.

Ocular neovascularization is a hallmark of several sight-threatening diseases, including diabetic retinopathy and age-related macular degeneration. Currently, available treatments are limited and often associated with side effects. Therefore, a novel approach to ocular neovascularization treatment through utilization of polymersomes from self-assembled sphingosine-grafted hyaluronic acid (HA-Sph) amphiphilic polymers is presented. The polymersomes are generated in spherical morphologies and sizes between 97.95 - 161.9 nm with homogenous size distributions. Experiments reveal that HA-Sph polymersomes, with concentrations ≥150 µg mL-1, significantly inhibit the proliferation of human umbilical vein endothelial cells (HUVECs), while concurrently promoting the proliferation of retinal pigment epithelial cells. The polymersomes demonstrate gradual disintegration in vitro, leading to sustained release of sphingosine, which prolongs the inhibition of HUVEC proliferation (from 87.5% at 24 h to 35.2% viability at 96 h). The efficacy of polymersomes in inhibiting angiogenesis is confirmed through tube formation assay, revealing a substantial reduction in tube length compared to the control group. The findings also validate the ocular penetration capability of polymersomes through ex vivo whole porcine eye ocular penetration study, indicating their suitability for topical administration. Potentially, HA-Sph polymersomes can be harnessed to develop intricate drug delivery systems that protect the retina and effectively treat ocular diseases.

Limitations associated with conventional bone substitutes such as autografts, increasing demand for bone grafts, and growing elderly population worldwide necessitate development of unique materials as bone graft substitutes. Bone tissue engineering (BTE) would ensure therapy advancement, efficiency, and cost-effective treatment modalities of bone defects. One way of engineering bone tissue scaffolds by mimicking natural bone tissue composed of organic and inorganic phases is to utilize polysaccharide-bioceramic hybrid composites. Polysaccharides are abundant in nature, and present in human body. Biominerals, like hydroxyapatite are present in natural bone and some of them possess osteoconductive and osteoinductive properties. Ion doped bioceramics could substitute protein-based biosignal molecules to achieve osteogenesis, vasculogenesis, angiogenesis, and stress shielding. This review is a systemic summary on properties, advantages, and limitations of polysaccharide-bioceramic/ion doped bioceramic composites along with their recent advancements in BTE.

Hydroxyapatite (HAp) is the most well-known bioceramic and widely utilized in bone tissue regeneration. Hydroxyapatite is biocompatible and bioactive however, it lacks osteogenesis, angiogenesis, and antibacterial properties. In the current study, we synthesized and evaluated a novel nickel (Ni) and silver (Ag) codoped hydroxyapatite (HAp) in comparison to undoped HAp and individually doped HAp samples. Extensive physicochemical characterizations like XRD, TEM, FE-SEM/EDS, FTIR, Raman spectroscopy, and TGA were performed, confirming the crystal structure and morphology of the synthesized HAp samples. All HAp samples exhibited elongated spherical-like nanoparticle morphologies with lengths between 34 and 44 nm and widths between 21 and 26 nm. The presence of dopant atoms, Ag and Ni, were observed in the doped/codoped HAp samples by EDS elemental mapping. Biocompatibility assessments using pre-osteoblast cells indicated high cell viability for all the doped and undoped HAp samples. Osteoinduction potential through alkaline phosphatase (ALP) activity measurements and alizarin red S (ARS) staining revealed enhanced calcium deposition in the presence of Ni-Ag codoped HAp compared to other HAp samples and control groups. This highlights the importance of Ni-Ag codoping in promoting osteogenesis, surpassing the effects of silver doped HAp and nickel doped HAp. The potential of this novel Ni-Ag codoped HAp to induce osteogenesis in pre-osteoblast cells makes it a promising material for various applications in bone tissue engineering.

Lentivirus and adeno-associated viruses are invaluable tools for biotechnology applications due to their genetic material delivery abilities both in vitro and in vivo. However, their large-scale productions with Good Manufacturing Practices yield low efficiency when adherent and serum dependent HEK293 (Human Embryonic Kidney) cells are used as the host. To increase production efficiency, HEK293 cells are adapted to grow in suspension using commercially available and chemically defined serum-free mediums. Suspended cells can be transiently transfected for viral vector production; however, significant improvements are still needed to increase yield and thereby cost effectiveness. Here, we evaluated four most preferred commercially available mediums that are IVY, FreeStyle293, LV-MAX, and BalanCD HEK293 for the transient transfection feasibility of lentiviral (LV) and adeno-associated virus serotype 2 (AAV2) production in FlorabioHEK293 suspension cells. The highest transfection efficiency was over 90% and obtained by using polyethyleneimine (PEI) 25 K and by media adaptation in IVY without using any transfection enhancer. For the first time the feasibility of HEK293 cells, which were adapted to grow in suspension culture by Florabio and IVY media, were tested for virus production. This study demonstrates the best transfection medium for scalable and optimized production of Lentivirus and Adeno-Associated Virus in suspended HEK293 cell culture.

Bone repair is a self-healing process. However, critical-sized bone defects need bone augmentation where bone tissue engineering plays vital role. Bone tissue Engineering (BTE) requires unique combinations of scaffolds, cells, and bio-signal molecules. Bone scaffold materials should be biocompatible, bioresorbable and exhibit biomimetic properties. Natural polymers, acquiring cell binding motives, producing nontoxic degradation products and tunable properties are ideal materials. Anionic polysaccharides of natural origin mimic mammalian ECM components and even the group called GAGs (Glycosaminoglycan) are actual components of ECM possessing various functions including cell adhesion, cell signaling, maintenance of homeostasis and inflammation control. Among them, anionic polysaccharides provide stabilization and sustained release of growth factors (GFs), porosity, calcium phosphate nucleation site, viscoelasticity, and water retention. Therefore, anionic polysaccharides are unique biomaterials for BTE. In this review, we have summarized the highlights of bone tissue engineering and recent applications of anionic polysaccharides in BTE.

Effective mixing is essential for a wide range of microfluidics applications. Passive micromixers have attracted much attention during recent years due to their low-cost and simple fabrication procedures with less power input in their implementation to high-throughput microfluidics platforms. Increasing the efficiency of micromixers is possible with an optimum geometry of inertial microfluidic channels, which utilize Dean vortices and Dean flows for the enhancement of mixing. Recently, micromixers with curved microchannels have been introduced to the literature. Yet, the enormous potential of elliptical spiral microchannels has not been adequately revealed. This study aims to assess the mixing performance of five-loop spiral polydimethylsiloxane micromixers with spiral structures and elliptic structures, which have different initial aspect ratios with varying radii of curvature along the channel. The performances of these micromixers were evaluated by comparing the mixing indices and intensity profiles obtained from inverted fluorescence microscopy images over a broad range of Reynolds numbers between 10 and 100. Elliptical spiral microchannels were able to provide mixing indices up to 98% at a Reynolds number of 20. Overall, the utilization of ellipse-shaped microchannels appear to provide a passive control over the mixing performance at several locations through the microchannel.

Abstract As an elastomer, poly(dimethylsiloxane) (PDMS) is used in various applications such as wearable technology and sealants, and is especially preferred in microelectromechanical device production due to its advantage in fabrication of microstructures. However, some of its applications such as sensor-based or electrode-based are limited due to its insulator aspect. Various conductive nanomaterials such as carbon nanotubes (CNTs), graphene, graphite, carbon black, and silver nanoparticles were incorporated into the PDMS matrix for the production of conductive nanocomposites. In this study, we produced highly conductive PDMS nanocomposites by addition of multiwalled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) in a three-dimensional network. Due to the synergistic effect between CNTs and GNPs inside a polymeric matrix, we expected to obtain PDMS nanocomposites more conductive than nanocomposites with only CNTs. Additionally, we investigated the effect of sulfuric acid treatment on the electrical conductivity and surface composition of prepared PDMS/MWCNT/GNP nanocomposites. Results indicated that the electrical conductivity in sulfuric acid-treated samples was significantly higher than in untreated samples. Levels of conductivity in the range of 270.7–1074.8 S/m were achieved; the higher ones were the samples treated with sulfuric acid solution.

The current COVID-19 pandemic has affected more than 100 million people and resulted in morbidity and mortality around the world. Even though the disease caused by SARS-CoV-2 is characterized by respiratory tract involvement, previous and recent data also indicates ocular manifestation. Not surprisingly, cell entry point of the virus, ACE2 receptor, is widely expressed in ocular tissues ranging from conjunctiva to retina. Despite the sensibility of ocular tissues, the sophisticated defense mechanism of the eye might eliminate viral transmission. Nevertheless, the potential of systemic transmission through the nasolacrimal duct may not be eliminated. In the case of ocular involvement, the disease outcomes might be as treatable as conjunctivitis or as serious as retinal degeneration and the treatment regimen vary accordingly. Within these contingencies, our aim with this chapter is to shed light on molecular bases of SARS-CoV-2 infection, systemic invasiveness following ocular transmission, manifestation and permanent effects on ocular tissues.

The eye is a complex organ consisting of several protective barriers and particular defense mechanisms. Since this organ is exposed to various infections, genetic disorders, and visual impairments it is essential to provide necessary drugs through the appropriate delivery routes and vehicles. The topical route of administration, as the most commonly used approach, maybe inefficient due to low drug bioavailability. New generation safe, effective, and targeted drug delivery systems based on nanocarriers have the capability to circumvent limitations associated with the complex anatomy of the eye. Nanotechnology, through various nanoparticles like niosomes, liposomes, micelles, dendrimers, and different polymeric vesicles play an active role in ophthalmology and ocular drug delivery systems. Niosomes, which are nano-vesicles composed of non-ionic surfactants, are emerging nanocarriers in drug delivery applications due to their solution/storage stability and cost-effectiveness. Additionally, they are biocompatible, biodegradable, flexible in structure, and suitable for loading both hydrophobic and hydrophilic drugs. These characteristics make niosomes promising nanocarriers in the treatment of ocular diseases. Hereby, we review niosome based drug delivery approaches in ophthalmology starting with different preparation methods of niosomes, drug loading/release mechanisms, characterization techniques of niosome nanocarriers and eventually successful applications in the treatment of ocular disorders.

Nanotechnology offers many advantages in various fields of science. In this regard, nanoparticles are the essential building blocks of nanotechnology. Recent advances in nanotechnology have proven that nanoparticles acquire a great potential in medical applications. Formation of stable interactions with ligands, variability in size and shape, high carrier capacity, and convenience of binding of both hydrophilic and hydrophobic substances make nanoparticles favorable platforms for the target-specific and controlled delivery of micro- and macromolecules in disease therapy. Nanoparticles combined with the therapeutic agents overcome problems associated with conventional therapy; however, some issues like side effects and toxicity are still debated and should be well concerned before their utilization in biological systems. It is therefore important to understand the specific properties of therapeutic nanoparticles and their delivery strategies. Here, we provide an overview on the unique features of nanoparticles in the biological systems. We emphasize on the type of clinically used nanoparticles and their specificity for therapeutic applications, as well as on their current delivery strategies for specific diseases such as cancer, infectious, autoimmune, cardiovascular, neurodegenerative, ocular, and pulmonary diseases. Understanding of the characteristics of nanoparticles and their interactions with the biological environment will enable us to establish novel strategies for the treatment, prevention, and diagnosis in many diseases, particularly untreatable ones.

Polydimethylsiloxane (PDMS) is an insulator and it is commonly used in fabrication of micro-structures but there is a need of electrical conductive PDMS. Therefore, this research is mainly focused on producing PDMS nanocomposites with high electrical conductivity. Thus, we produced highly conductive PDMS nanocomposites which were filled with multiwalled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs). Due to the synergistic effect between CNTs and GNPs inside a polymeric matrix, we expected to obtain more conductive nanocomposites than PDMS nanocomposite filled with only CNTs. Additionally, we investigated the effect of sulfuric acid treatment to surface composition and electrical conductivity of prepared PDMS/MWCNT/GNP nanocomposites. Results indicated that electrical conductivity of sulfuric acid-treated samples was significantly higher than untreated samples. The level of conductivity in the range of from 270.7 to 1074.9 S/m was obtained, and the higher ones are the samples treated with acid solution.