Hyaluronan-Sphingosine Polymersomes for Treatment of Ocular Neovascularization: Synthesis and Evaluation.

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.

Enhanced properties of nickel-silver codoped hydroxyapatite for bone tissue engineering: Synthesis, characterization, and biocompatibility evaluation.

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 co-doping 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.

Polysaccharide-bioceramic composites for bone tissue engineering: A review.

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.

A feasibility study of different commercially available serum-free mediums to enhance lentivirus and adeno-associated virus production in HEK 293 suspension cells.

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. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00551-1.

Bone tissue engineering: Anionic polysaccharides as promising scaffolds.

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.

Therapeutic Nanoparticles and Their Targeted Delivery Applications.

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.