Nanofibrous Polycaprolactone Membrane with Bioactive Glass and Atorvastatin for Wound Healing: Preparation and Characterization.

Skin wound healing is one of the most challenging processes for skin reconstruction, especially after severe injuries. In our study, nanofiber membranes were prepared for wound healing using an electrospinning process, where the prepared nanofibers were made of different weight ratios of polycaprolactone and bioactive glass that can induce the growth of new tissue. The membranes showed smooth and uniform nanofibers with an average diameter of 118 nm. FTIR and XRD results indicated no chemical interactions of polycaprolactone and bioactive glass and an increase in polycaprolactone crystallinity by the incorporation of bioactive glass nanoparticles. Nanofibers containing 5% w/w of bioactive glass were selected to be loaded with atorvastatin, considering their best mechanical properties compared to the other prepared nanofibers (3, 10, and 20% w/w bioactive glass). Atorvastatin can speed up the tissue healing process, and it was loaded into the selected nanofibers using a dip-coating technique with ethyl cellulose as a coating polymer. The study of the in vitro drug release found that atorvastatin-loaded nanofibers with a 10% coating polymer revealed gradual drug release compared to the non-coated nanofibers and nanofibers coated with 5% ethyl cellulose. Integration of atorvastatin and bioactive glass with polycaprolactone nanofibers showed superior wound closure results in the human skin fibroblast cell line. The results from this study highlight the ability of polycaprolactone-bioactive glass-based fibers loaded with atorvastatin to stimulate skin wound healing.

Strength and bioactivity of PEEK composites containing multiwalled carbon nanotubes and bioactive glass.

Polyetheretherketone (PEEK) polymer is a widely accepted implantable biomaterial in the biomedical field. However, PEEK has a low elastic modulus (E-modulus) as well as a bio-inert nature which is not conductive to rapid bone cell attachment, hence, producing delayed or weak bone-implant integration. Multiwalled carbon nanotubes (MWCNTs) represent one of the strongest known materials that could be added to a polymer to improve its mechanical properties. Bioactive glasses (BGs) can form hydroxyapatite deposits on their surfaces and form a tight bond with the bone, thus, their incorporation into the PEEK matrix may improve its bioactivity. METHODS: Eight groups were formulated according to the type and percentage of modification of PEEK by MWCNTs and BGs. Group 1: Pure PEEK (P), Group 2: P + 3% MWCNTs (PC3), Group 3: P + 5% MWCNTs (PC5), Group 4: P + 5% BGs (PG5), Group 5: P + 10% BGs (PG10), Group 6: P + 3% MWCNTs + 5% BGs (PC3G5), Group 7: P + 3% MWCNTs + 10% BGs (PC3G10), and Group 8: P + 5% MWCNTs + 5% BGs (PC5G5). Characterization of the vacuum-pressed PEEK and PEEK composite specimens was done using FE-SEM, EDS, FT-IR and TF-XRD. Three-point load test was done to obtain the flexural strength (F.S) and the E-modulus of the specimens. Wettability was determined by measuring the contact angle with distilled water. In-vitro bioactivity was determined after immersion of specimens in simulated body fluid (SBF). Moreover, the effect of the specimens on osteoblastic cell viability was evaluated. RESULTS: Three-point load test results have shown an improvement in both F.S. and E-modulus for groups PC5, PC3G5 and PC5G5. The lowest contact angle was obtained for group PC5G5 followed by the PC3G10 group. All specimens containing BGs showed the formation of hydroxyapatite-like deposits after their immersion in SBF, as well as an improvement in osteoblastic cell viability compared to PEEK. CONCLUSION: PC3G10, PC3G5 and PG10, groups are promising for the fabrication of patient-specific implants that can be used in low-stress-bearing areas.

N-Rich, Polyphenolic Porous Organic Polymer and Its In Vitro Anticancer Activity on Colorectal Cancer.

N-rich organic materials bearing polyphenolic moieties in their building networks and nanoscale porosities are very demanding in the context of designing efficient biomaterials or drug carriers for the cancer treatment. Here, we report the synthesis of a new triazine-based secondary-amine- and imine-linked polyphenolic porous organic polymer material TrzTFPPOP and explored its potential for in vitro anticancer activity on the human colorectal carcinoma (HCT 116) cell line. This functionalized (-OH, -NH-, -C=N-) organic material displayed an exceptionally high BET surface area of 2140 m2 g-1 along with hierarchical porosity (micropores and mesopores), and it induced apoptotic changes leading to high efficiency in colon cancer cell destruction via p53-regulated DNA damage pathway. The IC30, IC50, and IC70 values obtained from the MTT assay are 1.24, 3.25, and 5.25 µg/mL, respectively.

An in vitro / in vivo release test of risedronate drug loaded nano-bioactive glass composite scaffolds.

Three-dimensional (3D) matrices scaffolds play a noteworthy role in promoting cell generation and propagation. In this study, scaffolds prepared from chitosan/polyvinyl alcohol loaded with/without an osteoporotic drug (risedronate) and nano-bioactive glass (nBG) have been developed to promote healing of bone defects. The scaffolds were characterized by scanning electron microscopy (SEM), porosity test as well as mechanical strength. The pattern of drug release and ability to promote the proliferation of Saos-2osteosarcoma cells had also been reported. Osteogenic potential of the scaffolds was evaluated by testing their effect on healing critical-sized dog's mandibular bone defects. Increasing chitosan and nBG in the porous scaffolds induced decrease in drug release, increased the scaffold's strength and supported their cell proliferation, alkaline phosphatase (ALP) activities, as well as increased calcium deposition. Histological and histomorphometric results demonstrated newly formed bone trabeculae inside critical-sized mandibular defects when treated with scaffolds. Trabecular thickness, bone volume/tissue volume and the percentage of mature collagen fibers increased in groups treated with scaffolds loaded with 10% nBG and risedronate or loaded with 30% nBG with/without risedronate compared with those treated with non-loaded scaffolds and empty control groups. These findings confirmed the potential osteogenic activity of chitosan/polyvinyl alcohol-based scaffolds loaded with risedronate and nBG.

Efficient drug delivery vehicles of environmentally benign nano-fibers comprising bioactive glass/chitosan/polyvinyl alcohol composites.

Nano-fiber composites have shown promising potential in biomedical and biotechnological applications. Herein, novel nano-fiber composites constituting a blend of polyvinyl alcohol (PVA) and chitosan (CS) along with different weight ratios of nano-bioactive glass (BG) were prepared by electrospinning. Nano-fibers incorporating 10% (by wt.) of BG were uniform, dense and defect-free with a diameter of 20-125 nm. The model osteoporotic drug (Risedronate sodium) was blended with the electrospinning forming solution and the in-vitro drug release was further studied. About 30% of the drug was released after only 30 min and the release pattern was sustained over 96 h. Drug release took place through a two-stage intra-particle diffusion mechanism. BG-incorporated nano-fibers markedly retarded the drug release profile relative to their BG-free counterparts. They also enhanced the drug release efficiency by releasing 93 ± 4% of the drug. The developed nano-fiber composites can be potentially used as drug-delivery vehicles due to their efficiency and sustained drug release capacity.

Bioactive glass doped with noble metal nanoparticles for bone regeneration: in vitro kinetics and proliferative impact on human bone cell line.

This work investigates the bioactivity of novel silver-doped (BG-Ag) and gold-doped (BG-Au) quaternary 46S6 bioactive glasses synthesized via a semi-solid-state technique. A pseudo-second-order kinetic model successfully predicted the in vitro uptake kinetic profiles of the initial ion-exchange release of Ca in simulated body fluid, the subsequent Si release, and finally, the adsorption of Ca and P onto the bioactive glasses. Doping with silver nanoparticles enhanced the rate of P uptake by up to approximately 90%; whereas doping with gold nanoparticles improved Ca and P uptake rates by up to about 7 and 2 times, respectively; as well as Ca uptake capacity by up to about 19%. The results revealed that the combined effect of Ca and Si release, and possibly the release of silver and gold ions into solution, influenced apatite formation due to their effect on Ca and P uptake rate and capacity. In general, gold-doped bioactive glasses are favoured for enhancing Ca and P uptake rates in addition to Ca uptake capacity. However, silver-doped bioactive glasses being less expensive can be utilized for applications targeting rapid healing. In vitro studies showed that BG, BG-Ag and BG-Au had no cytotoxic effects on osteosarcoma MG-63 cells, while they exhibited a remarkable cell proliferation even at low concentration. The prepared bioactive glass doped with noble metal nanoparticles could be potentially used in bone regeneration applications.

In-situ forming chitosan implant-loaded with raloxifene hydrochloride and bioactive glass nanoparticles for treatment of bone injuries: Formulation and biological evaluation in animal model.

In-situ forming implants receive great attention for repairing serious bone injuries. The aim of the present study was to prepare novel chitosan in-situ forming implants (CIFI) loaded with bioactive glass nanoparticles and/or raloxifene hydrochloride (RLX). Incorporating raloxifene hydrochloride (RLX) as a selective estrogen receptor modulator was essential to make use of its anti-resorptive properties. The prepared formulae were tested for their in-vitro gelation time, drug release, injectability, rheological properties, erosion rate and morphological properties. Results revealed that the formulation composed of 1% (w/v) chitosan with 2% (w/v) NaHCO3 and 1% (w/v) bioactive glass nanoparticles (CIFI-BG) possessed the most sustained drug release profile which extended over four months with low burst release effect compared to the same formulation lacking bioactive glass nanoparticles (CIFI). Selected formulations were tested for their ability to enhance bone regeneration in induced puncture in rate tibia. Results declared that these formulations were able to enhance bone regeneration after 12 weeks in comparison to the untreated tibial punctures and that containing bioactive glass could be considered as novel approach for treatment of serious bone injuries which require long term treatment and internal mechanical bone support during healing.

Long lasting in-situ forming implant loaded with raloxifene HCl: An injectable delivery system for treatment of bone injuries.

Bone injury is very serious in elder people or osteoporotic patients. In-situ forming implants (IFI) for bone rebuilding are usually poly-lactic-co-glycolic acid (PLGA)-based, which have a burst release effect. This study aimed to prepare novel liquid lipid-based PLGA-IFI loaded with raloxifene hydrochloride for prolonged non-surgical treatment of bone injuries by applying solvent-induced phase inversion technique. Labrasol® and Maisine® were added to the selected IFI forming long lasting lipid-based IFI (LLL-IFI). The formulations were characterized by analysing their in-vitro drug release, solidification time, injectability, rheological properties, and DSC in addition to their morphological properties. Results revealed that the LLL-IFI composed of 10%w/v PLGA with a lactide to glycolide ratio of 75:25 with ester terminal and 10% Maisine® possessed the most sustained drug release and lowest burst effect, as well as delayed pore formation compared to its counterpart lacking Maisine®. The selected LLL-IFI and PLGA-IFI formulations were tested for their capability to enhance bone regeneration in bone injuries induced in rats. Both formulations succeeded in healing the bones completely with the superiority of LLL-IFI in the formation of well-organized bone structures lacking fibrous tissues. The results suggest that LLL-IFI and PLGA-IFI are innovative approaches for treating critical and non-critical sized bone injuries.

Correction: A new triazine based π-conjugated mesoporous 2D covalent organic framework: its in vitro anticancer activities.

Correction for 'A new triazine based π-conjugated mesoporous 2D covalent organic framework: its in vitro anticancer activities' by Sabuj Kanti Das et al., Chem. Commun., 2018, 54, 11475-11478.

A new triazine based π-conjugated mesoporous 2D covalent organic framework: its in vitro anticancer activities.

We report a new highly crystalline 2D π-conjugated hexagonal mesoporous covalent organic framework material, TrzCOF, through the solvothermal polycondensation of 1,3,5-tri(4-formylbiphenyl) benzene [Ph7(CHO)3, TFBPB] with 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and it displayed excellent anticancer activity for human colorectal carcinoma HCT-116 cells.

In vitro kinetic investigations on the bioactivity and cytocompatibility of bioactive glasses prepared via melting and sol-gel techniques for bone regeneration applications.

This work investigates and compares the influence of the synthesis process on the in vitro bioactivity of two quaternary bioactive glasses prepared via melting and sol-gel (SG) techniques. The two glasses are named MG and SG, respectively. Powder samples were soaked in simulated body fluid for different time intervals to study the kinetics of Ca and P uptake onto their surface as well as Si release. The uptake kinetics followed the pseudo-second order model, and the kinetic parameters in addition to the initial rates were estimated. MG manifested higher Ca uptake capacity than SG which could be attributed to the presence of a residual organic layer capping the surface of SG, as was confirmed by Fourier transform infrared and nuclear magnetic resonance analyses. However, higher rate of Ca uptake was exhibited by SG probably due to its higher reactivity that resulted from its smaller nano-size and higher negative charge as was evident from transmission electron microscopy and dynamic light scattering measurements, respectively. Furthermore, MG showed slightly higher P uptake capacity and lower amount of Si release. Initial rates of Ca and P uptakes onto SG as well as Si release from SG exceeded those of MG. Human bone osteosarcoma cells (Saos-2) were co-cultured with both MG and SG glasses and the latter showed higher alkaline phosphatase activity and higher cell growth induction. The results showed the promising potential of using both bioactive glasses in bone regeneration. However, the choice of the appropriate bioactive glass depends on the targeted applications.

Bioactive/Natural Polymeric Scaffolds Loaded with Ciprofloxacin for Treatment of Osteomyelitis.

Local delivery of antibiotic into injured bone is a demand. In this work, different scaffolds of chitosan (C) with or without bioactive glass (G) were prepared using the freeze-drying technique in 2:1, 1:1, and 1:2 weight ratios. Chitosan scaffolds and selected formulas of chitosan to bioglass were loaded with ciprofloxacin in 5%, 10%, and 20% w/w. Scaffold morphology showed an interconnected porous structure, where the glass particles were homogeneously dispersed in the chitosan matrix. The kinetic study confirmed that the scaffold containing 1:2 weight ratio of chitosan to glass (CG12) showed optimal bioactivity with good compromise between Ca and P uptake capacities and Si release rate. Chitosan/bioactive glass scaffolds showed larger t 50 values indicating less burst drug release followed by a sustained drug release profile compared to that of chitosan scaffolds. The cell growth, migration, adhesion, and invasion were enhanced onto CG12 scaffold surfaces. Samples of CG12 scaffolds with or without 5% drug induced vascular endothelial growth factor (VEGF), while those containing 10% drug diminished VEGF level. Only CG12 induced the cell differentiation (alkaline phosphatase activity). In conclusion, CG12 containing 5% drug can be considered a biocompatible carrier which would help in the localized osteomyelitis treatment.

Injectable nanoamorphous calcium phosphate based in situ gel systems for the treatment of periapical lesions.

Nonsurgical local treatment of a periapical lesion arising from trauma or bacterial infection is a promising innovative approach. The present study investigated the feasibility of developing injectable amorphous calcium phosphate nanoparticles (ACP NPs) and ACP NPs loaded with an anti-inflammatory drug; ibuprofen (IBU-ACP NPs) in the form of thermoreversible in situ gels to treat periapical lesions with the stimulation of bone formation. NPs were produced by a spray-drying technique. Different formulations of Poloxamer 407 were incorporated with/without the produced NPs to form injectable gels. A drug release study was carried out. A 3 month in vivo test on a dog model also was assessed. Results showed successful incorporation of the drug into the NPs of CP during spray drying. The particles had mean diameters varying from 100 to 200 nm with a narrow distribution. A drug release study demonstrated controlled IBU release from IBU-ACP NPs at a pH of 7.4 over 24 h. The gelation temperature of the injectable in situ gels based on Poloxamer 407 was measured to be 30 °C. After 3 months of implantation in dogs, the results clearly demonstrated that the inclusion of ACP NPs loaded with IBU showed high degrees of periapical bone healing and cementum layer deposition around the apical root tip.

A quantitative approach for studying the bioactivity of nanohydroxyapatite/gold composites.

This work describes a quantitative kinetic approach to assess the in vitro bioactivity of gold-doped hydroxyapatite-polyvinyl alcohol nanocomposites. The surface morphology of the in situ prepared nanocomposites as characterized by transmission electron microscopy (TEM) revealed a rod-like shape. Differential thermal analysis-thermogravimetric (DTA-TG), and fourier transformed infrared spectroscopy (FTIR) as well as zeta potential measurements of the prepared nanocomposites were carried out. Uptake profiles of Ca and P were studied onto nanocomposites of different gold concentrations after their soaking in simulated body fluid and they best followed the pseudo second-order kinetic model. The highest uptakes of both Ca and P were obtained using the nanocomposite with the lowest concentration of gold. Furthermore, sorption mechanism was described by the intraparticle diffusion model where pore diffusion was found to be the rate limiting step. The prepared nanocomposites have promising potential in orthopedic and tissue engineering applications because of their high capacity and fast uptake for Ca and P, which form apatite.

Kinetic evaluation study on the bioactivity of silver doped hydroxyapatite-polyvinyl alcohol nanocomposites.

This work investigates the effect of adding silver nanoparticles (NPs) in ppm on the bioactivity of hydroxyapatite/polyvinyl alcohol nanocomposites (HAV). HAV prepared by an in situ biomimetic approach was doped with different concentrations of silver NPs (HAV-Ag), and the formed powder samples were characterized by different techniques such as Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-EOS), X-ray diffraction, transmission electron microscope, and Fourier Transform Infrared Spectroscopy. Bioactivity was evaluated in simulated body fluid through studying the kinetics of Ca and P uptake onto the different HAV-Ag nanocomposites. Uptake profiles of Ca and P were well described by a pseudo-second order kinetic model, and the obtained kinetic parameters confirmed that the highest uptake capacities were achieved by adding less than 0.001 ppm of silver NPs which is an amount not detectable by ICP. Furthermore, HAV-Ag nanocomposites were shown to be non-toxic as well as have a strong antibacterial effect. Silver NPs significantly enhanced the bioactivity of HAV nanocomposites and thus the developed nanocomposites promise to be excellent biomaterials for bone and reconstructive surgery applications.

Chemical characterization of some substituted hydroxyapatites.

Synthetic multi-substituted hydroxyapatite nano powders containing silicon and or carbonate prepared by a wet chemical method. The process parameters are set up to allow the simultaneous substitution of carbonate and silicon ions in the place of phosphorus. The chemical and structural characterizations of the prepared powders are determined with the aid of; XRF, ICP, XRD and FTIR. The results show that, the ion substitution in the crystal lattice of HA caused a change in the unit cell dimensions and affected the degree of crystallization of the produced powders. The apatite formation abilityy of the prepared discs from the synthesized powders is determined by immersing in SBF solution for different periods. The degree of ion release was determined in the obtained solutions. The examined surface of the immersed discs under SEM and analyzed by CDS showed a more dense HA layer than those of un-substituted ones. The HA with the substituted silicon and carbonate ions, showed the highest solubility with greater rate of ion release, compared with carbonate-free powder. All prepared powders took sodium ion from the SBF solution during immersion, which was not recorded before.