Bone formation by Irisin-Poly vinyl alchol modified bioglass ceramic beads in the rabbit model.

In the aging society, slow bone regeneration poses a serious hindrance to the quality of life. To deal with this problem, in this study, we have combined irisin with the bioglass regular beads to enhance the bone regeneration process. For this purpose, highly porous bioglass was obtained as spherical beads by using sodium alginate. The bioglass was evaluated by various analytical techniques such as SEM, EDS, XRD, and pore size distribution. The results depicted that porous bioglass was prepared correctly and SEM analysis showed a highly porous bioglass was formulated. On this bioglass, irisin was loaded with the assistance of polyvinyl alcohol (PVA) in three concentrations (50 ng/ml, 100 ng/ml, and 150 ng/ml per 1 g of bioglass). SEM analysis showed that pores are covered with PVA. The irisin release profile showed a sustained release over the time period of 7 days. In vitro, biocompatibility evaluation by the MC3T3E1 cells showed that prepared bioglass and irisin loaded bioglass (BGI50, BGI100, and BG150) are highly biocompatible. Alizarin Red staining analysis showed that after 2 weeks BGI50 samples showed highest calcium nodule formation. In vivo in the rabbit femur model was conducted for 1 and 2 months. BGI150 samples showed highest BV/TV ratio of 37.1 after 2 months. The histological data showed new bone formation surrounding the beads and with beads loaded with irisin. Immunohistochemistry using markers OPN, RUNX, COL, and ALP supported the osteogenic properties of the irisin-loaded bioglass beads. The results indicated that irisin-loaded bioglass displayed remarkable bone regeneration.

Selective Self-Assembly of a Rectangular Ruthenium Supramolecule from an Unsymmetrical Bridging Unit.

Herein, we report the synthesis of an unsymmetrical diruthenium bridging unit containing a multidentate oxamate ligand and the subsequent formation of a rectangular supramolecule. The reaction of oxamate 1, 2-((4-bromo-2,6-dimethylphenyl)amino)-2-oxo-acetic acid, and [(p-cymene)RuCl2]2 affords a novel unsymmetrical diruthenium acceptor clip 2, where two ruthenium metal centers are ligated with either [O,O] or [N,O]. The molecular clip 2 and bipyridine donor self-assemble to form two-dimensional rectangular supramolecule 3. Self-assembly can produce seven possible isomers depending on the position of the substituted bromoaryl groups. However, 1H NMR spectroscopic investigation indicated only two different isomers in the reaction mixture. A single isomer is isolated via crystallization, and X-ray crystallography confirms that the product is a C1 symmetric two-dimensional rectangular supramolecule, in which two bromoaryl groups are located in the farthest position from each other. Theoretical calculations suggest that the self-assembly of supramolecule 3 occurred via 1:1 adducts of the diruthenium molecular clip and bipyridine as an intermediate to predominantly form a single isomer.

Metal II complexes of ethambutol as good enzyme inhibitor and promising antioxidant.

Ethambutoldihydrogenchloride (EMB) with chemical formula C10H24N2O2.2HCl is ethane-1,2-diamine in which one hydrogen attached to each of the nitrogen is substituted by a 1-hydroxybutan-2-yl group (S,S-configuration). It is an FDA approved drug and has been used for treatment of tuberculosis since 1960's. Prolong use of EMB has a side effect of visual impairment and in literature it is related with the depletion of Zn metal from the body. As it is a good chelating agent, many metal II complexes have been synthesized with anti-tubercular activity. The purpose of this work was to synthesize metal II complexes of EMB and to evaluate their antioxidant activity along with enzyme inhibition activity (acetylcholine esterase and protease). The metals used for complex formation were Co, Zn, Fe, Cu and Ni. IR spectral data and physical parameters supported the complex formation. The obtained results showed the synthesized complexes as notable antioxidants and enzyme inhibitors.

Evaluation of Aloe Vera Gel Combined with Cinnamon Oil with Antibacterial Activity for Wound Healing Application.

Treatment of chronic wounds has been shifted to traditional approaches due to surge in antibiotic resistance. Wounds that fail to heal satisfactorily may result in the amputation of the organ. In this research work, cinnamon oil (CO) and aloe vera (AV) that have been traditionally used as antibacterial agents are combined in a unique gel (COVA) and its antibacterial activity has been evaluated through in vitro and in vivo studies. Antibacterial activity was measured through disk diffusion and agar dilution method against Pseudomonas aeruginosa and Staphylococcus aureus. To check antibacterial and wound healing activity, diabetic excision wound healing rat model was used. Wound closure, wound contraction, tissue hydroxyproline content, antioxidant capacity (TAC), and malondialdehyde (MDA) level were monitored. The minimum inhibitory concentrations of CO + AV for bacterium P. aeruginosa and S. aureus were 100 and 200 µg/ml, respectively. After 14 days, the wounds covered with COVA therapy reached to nearly full wound closure (79% wound contraction) compared to control. The collagen content and level of TAC increased significantly (P < 0.05) in treated groups; therefore, 25% fast healing was observed in wounds treated with CO and AV gel combined. Reduced levels of tissue MDA were observed in all treated groups and specially wound covered with COVA (0.43 mM/mg in control vs 0.25 mM/mg in COVA). Histopathological examination also supported the outcomes. Significantly elevated increase in the level of hydroxyproline was found in rats of COVA treatment group (37.1 ± 0.44). Combination of CO and AV can be potentially used to prevent infection in wound; as these herbal agents not only inhibit the growth of pathogenic bacteria but also accelerate tissue repair.

ECM derivatized alginate augmenting bio-functionalities of lyophilized mat for skin and liver wound treatment.

Peptides and molecular residues sourced from the fragmentation of the extracellular matrix (ECM) can exacerbate a plethora of cellular functions. We selected a natural ECM-derived complex peptide mixture to functionalize sodium alginate. Three alginate derivatives (sodium alginate conjugated with ECM) SALE-1, SALE-2, and SALE-3 were synthesized using the lowest (10 % w/w), moderate (50 % w/w), and highest (100 % w/w) concentrations of ECM. Thereafter, they were used to fabricate three groups of mat scaffolds EMAT-1 (ECM derivatized alginate thrombin-mat), EMAT-2, and EMAT-3, respectively by the freeze-drying process. To enhance the hemostatic activity, thrombin was loaded onto the scaffolds. Another group, AT, without any derivatized alginate was additionally included in order to comparative analysis. Physical characteristics revealed that the porous mat scaffold showed enhancement in degradation and swelling ability with the increase in ECM content. The higher cell proliferation, migration, and cell viability were noticed in the higher ECM-containing samples EMAT-2 and EMAT-3. In vivo studies using rodent hepatic and rabbit ear models were carried out to ensure the hemostatic ability of the scaffolds. EMAT-2 and EMAT-3 demonstrate excellent liver regeneration ability in rat models. Moreover, the rat cutaneous wound model depicted that EMAT-3 dramatically elevated the skin's healing ability, thereby rendering it an excellent candidate for future clinical application in wound healing.

An agarose-based TOCN-ECM bilayer lyophilized-hydrogel with hemostatic and regenerative properties for post-operative adhesion management.

This study used a unique approach by developing a bilayer system that can simultaneously accomplish non-adhesion, hemostatic, and tissue regenerative properties. In this system, agarose was used as a carrier material, with an agarose-TEMPO-oxidized cellulose nanofiber (TOCN), (AT) layer acting as a non-adhesion layer and an Agarose-Extracellular matrix, (AE) layer acting as a tissue regenerative layer. Thrombin was loaded on the AE layer as an initiator of the healing process, by hemostasis. AT 1:4 showed 79.3 % and AE 1:4 showed 84.66 % cell viability initially confirming the biocompatible nature of the layers. The AE layer showed cell attachment and proliferation on its surface whereas on the AT layer, cells are visible but no attachment was observed. Furthermore, in vivo analysis was conducted. The non-adhesive layer was grafted between the cecum and peritoneal wall which showed that (AT 1:4) displayed remarkable non-adhesion properties as compared to a commercial product and the non-treated group. Hemostasis and tissue regeneration ability were evaluated using rat liver models. The bleeding time of AE 1:4TH was recorded as 160 s and the blood loss was 5.6 g. The results showed that (AE 1:4) displayed effective regeneration ability in the liver model after two weeks.

Evaluation of Gelatin/Hyaluronic Acid-Generated Bridging in a 3D-Printed Titanium Cage for Bone Regeneration.

3D-printed titanium (Ti) cages present an attractive alternative for addressing issues related to osteoporosis-induced fractures, accidental fractures, and spinal fusion surgery due to disc herniation. These Ti-based bone implants possess superior strength compared to other metals, allowing for versatile applications in orthopedic scenarios. However, when used as standalone solutions, certain considerations may arise, such as interaction with soft tissues. Therefore, to overcome these issues, the combination with hydrogel has been considered. In this study, to impart Ti with regenerative abilities a 3D-printed Ti cage was loaded with gelatin and hyaluronic acid (G-H) to improve the cell attachment ability of the Ti-based bone implants. The void spaces within the mesh structure of the 3D Ti cage were filled with G-H, creating a network of micro-sized pores. The filled G-H acted as the bridge for the cells to migrate toward the large inner pores of the 3D Ti cage. Due to the microporous surface and slow release of gelatin and hyaluronic acid, the biocompatibility of the coated Ti cage was increased with an elevation in osteoconduction as depicted by the up-regulation of bone-related gene expressions. The in vivo implantation in the rabbit femur model showed enhanced bone regeneration due to the coated G-H on the Ti cage compared to the pristine hollow Ti cage. The G-H filled the large holes of the 3D Ti cage that acted as a bridge for the cells to travel inside the implant and aided in the fast regeneration of bone.

Physico-biological and in vivo evaluation of irisin loaded 45S5 porous bioglass granules for bone regeneration.

In this study, we investigated the physico-biological and in-vivo evaluation of irisin loaded 45S5 bioglass bone graft for enhancing osteoblastic differentiation and bone regeneration in rat femur head defect model. Highly porous structure was obtained in the bioglass by burn-out process with varying the concentration of poly (methyl methacrylate) (PMMA) spheres. 10 % polyvinyl alcohol (PVA) was used as a binder for the sustain releasing of irisin on porous bioglass. Different concentrations of irisin were loaded on the selected bioglass samples and these were further evaluated for the biocompatibility and osteoblastic differentiation properties. The in vitro results demonstrated not only its biocompatibility but also that it stimulated pre-osteoblast differentiation. The in vivo data showed new bone formation as well as expression of osteogenic proteins like alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), and collagen-1 (Col-1). Our results support the use of irisin loaded bioglass for the use of early bone regeneration.

In-vivo bone remodeling potential of Sr-d-Ca-P /PLLA-HAp coated biodegradable ZK60 alloy bone plate.

Magnesium and its alloys are widely applied biomaterials due to their biodegradability and biocompatibility. However, rapid degradation and hydrogen gas evolution hinder its applicability on a commercial scale. In this study, we developed an Mg alloy bone plate for bone remodeling and support after a fracture. We further coated the Mg alloy plate with Sr-D-Ca-P (Sr dopped Ca-P coating) and Sr-D-Ca-P/PLLA-HAp to evaluate and compare their biodegradability and biocompatibility in both in vitro and in vivo experiments. Chemical immersion and dip coating were employed for the formation of Sr-D-Ca-P and PLLA-HAp layers, respectively. In vitro evaluation depicted that both coatings delayed the degradation process and exhibited excellent biocompatibility. MC3T3-E1cells proliferation and osteogenic markers expression were also promoted. In vivo results showed that both Sr-D-Ca-P and Sr-D-Ca-P/PLLA-HAp coated bone plates had slower degradation rate as compared to Mg alloy. Remarkable bone remodeling was observed around the Sr-D-Ca-P/PLLA-HAp coated bone plate than bare Mg alloy and Sr-D-Ca-P coated bone plate. These results suggest that Sr-D-Ca-P/PLLA-HAp coated Mg alloy bone plate with lower degradation and enhanced biocompatibility can be applied as an orthopedic implant.

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis.

Prostate cancer (PCa) is the second leading cause of cancer-causing death in the United States. As the most common malignancy in men, it is pertinent to explore whether novel immunotherapies may improve the quality of life and overall survival (OS) of patient populations. This systematic review and post hoc analysis curates a patient-by-patient pool of evidence adhering to PRISMA Statement 2020 guidelines. In total, 24 patients were analyzed for treatment history and associated variables including prostate-specific antigen (PSA) levels at diagnosis and post-treatment, Gleason score, secondary tumor locations, success/failure of therapy, and post-immunotherapy outcomes including OS. In total, 10 types of immunotherapies were identified with Pembrolizumab (among 8 patients) followed by IMM-101 (among 6 patients) being the most commonly administered. The mean OS for all patients was 27.8 months (24 patients) with the relatively highest mean OS reported with IMM-101 (56 months) followed by tumor-infiltrating lymphocytes (30 months). This research article provides critical insights into the evolving landscape of immunotherapies being tested for PCa and addresses gaps in oncological research to advance the understanding of PCa.

Poly(l-lactide)/polycaprolactone based multifunctional coating to deliver paclitaxel/VEGF and control the degradation rate of magnesium alloy stent.

Despite significant advancements made in cardiovascular stents, restenosis, thrombosis, biocompatibility, and clinical complications remain a matter of concern. Herein, we report a biodegradable Mg alloy stent with a dual effect of the drug (Paclitaxel) and growth factor (VEGF) release. To mitigate the fast degradation of Mg alloy, inorganic and organic coatings were formed on the alloy surface. The optimized hierarchal sequence of the coating was the first layer consisting of magnesium fluoride, followed by poly(l-lactide) and hydroxyapatite coating, and finally sealed by a polycaprolactone layer (MgC). PLLA and HAp were used to increase the adhesion strength and biocompatibility of the coating. Paclitaxel and VEGF were loaded in the final PCL layer (Mg-C/PTX-VEGF). As compared to bare Mg alloy (28 % weight loss), our MgC system showed (3.1 % weight loss) successful decrease in the degradation rate. Further, the in vitro biocompatibility illustrated the highly biocompatible nature of our drug and growth factor-loaded system. The in vivo results displayed that the drug loading decreased the inflammation and neointimal hyperplasia as indicated by the α-SMA and CD-68 antibody staining. The growth factor helped in the endothelialization which was established by the FLKI and ICAM antibody staining of the tissue.

Development of a novel polycaprolactone based composite membrane for periodontal regeneration using spin coating technique.

Guided bone regeneration (GBR) is known to prevent the development of soft tissue on the defect sites as well as support the new bone formation on the other end. In the present study, we developed a multilayer biodegradable membrane for GBR applications. The multilayer membrane is primarily composed of ß-tricalcium phosphate (TCP), polycaprolactone (PCL), and hyaluronic acid (HA), prepared by the spin-coating method. The triple layer system has PCL-TCP composite layer on top, a PCL layer in the middle, and PCL-HA as the bottom layer. The characterization of the PCL-TCP/PCL/PCL-HA by various techniques such as SEM, EDS, XRD, and FT-IR supported the uniform formation of the triple layers with an overall thickness of ∼ 72 µm. Multilayer composite membrane showed excellent physical parameters; neutral pH, high hydrophilicity, high swelling rate, low degradation rate, and high apatite formation after immersion in simulated body fluid (SBF) for 14 days. The multilayer membrane also exhibited biocompatibility which is evident by MTT assay and confocal images. The results suggested that the multilayer composite membrane has the potential for GBR applications.