Nanoscale borosilicate bioactive glass for regenerative therapy of full-thickness skin defects in rabbit animal model.

Bioactive glass (BG) occupies a significant position in the field of hard and soft tissue regeneration. Different processing techniques and formulas have been introduced to expand their regenerative, angiogenic, and antibacterial properties. In the present study, a new formula of bborosilicate bioactive glass nanofibers was prepared and tested for its wound-healing efficacy in a rabbit animal model. The glass formula ((1-2) mol% of B2O3 (68-69) mol% of SiO2, and (29-30) mol% of CaO) was prepared primarily by the sol-gel technique followed by the electrospinning technique. The material was characterized for its ultrastructure using scanning electron microscopy, chemical composition using FTIR, and its dynamic in vitro biodegradability using ICP-AES. Twelve rabbits were subjected to surgical induction of full-thickness skin defects using a 1 cm2 custom-made stainlessteel skin punch. The bioactive glass nanofibers were used as a grafting material in 6 experimental rabbits, while the defects in the remaining rabbits were considered as the negative control samples. All defects were assessed clinically for the decrease in wound size and clinical signs of healing and histologically for angiogenesis, collagen density, inflammatory response, cell recruitment, epithelial lining, and appendages at 1,2 and 3 weeks following the intervention. Structural analysis of the glass fibers confirmed their nano-size which ranged from 150 to 700 nm. Moreover, the chemical analysis confirmed the presence of SiO2 and B2O3 groups within the structure of the nanofibers. Additionally, dynamic biodegradation analysis confirmed the rapid degradation of the material starting from the first 24 h and rapid leaching of calcium, silicon, and boron ions confirming its bioactivity. The wound healing study of the nanofibrous scaffold confirmed its ability to accelerate wound healing and the closure rate in healthy rabbits. Histological analysis of the defects confirmed the angiogenic, regenerative and antibacterial ability of the material throughout the study period. The results unveil the powerful therapeutic properties of the formed nanofibers and open a new gate for more experimental and clinical applications.

Efficacy of Bioactive Glass Nanofibers Tested for Oral Mucosal Regeneration in Rabbits with Induced Diabetes.

The healing of oral lesions that are associated with diabetes mellitus is a matter of great concern. Bioactive glass is a highly recommended bioceramic scaffold for bone and soft tissue regeneration. In this study, we aimed to assess the efficacy of a novel formula of bioactive glass nanofibers in enhancing oral mucosal wound regeneration in diabetes mellitus. Bioactive glass nanofibres (BGnf) of composition (1-2) mol% of B2O3, (68-69) mol% of SiO2, and (29-30) mol% of CaO were synthesized via the low-temperature sol-gel technique followed by mixing with polymer solution, then electrospinning of the glass sol to produce nanofibers, which were then subjected to heat treatment. X-Ray Diffraction analysis of the prepared nanofibers confirmed its amorphous nature. Microstructure of BGnf simulated that of the fibrin clot with cross-linked nanofibers having a varying range of diameter (500-900 nm). The in-vitro degradation profile of BGnf confirmed its high dissolution rate, which proved the glass bioactivity. Following fibers preparation and characterization, 12 healthy New Zealand male rabbits were successfully subjected to type I diabetic induction using a single dose of intravenous injection of alloxan monohydrate. Two weeks after diabetes confirmation, the rabbits were randomly divided into two groups (control and experimental groups). Bilateral elliptical oral mucosal defects of 10 × 3.5 mm were created in the maxillary mucobuccal fold of both groups. The defects of the experimental group were grafted with BGnf, while the other group of defects considered as a control group. Clinical, histological, and immune-histochemical assessment of both groups of wounds were performed after one, two and three weeks' time interval. The results of the clinical evaluation of BGnf treated defects showed complete wound closure with the absence of inflammation signs starting from one week postoperative. Control defects, on the other hand, showed an open wound with suppurative exudate. On histological and immunohistochemical level, the BGnf treated defects revealed increasing in cell activity and vascularization with the absence of inflammation signs starting from one week time interval, while the control defects showed signs of suppurative inflammation at one week time interval with diminished vascularization. The results advocated the suitability of BGnf as bioscaffold to be used in a wet environment as the oral cavity that is full of microorganisms and also for an immune-compromised condition as diabetes mellitus.

Prospective treatment of Parkinson's disease by a siRNA-LDH nanoconjugate.

In the world, among the neurodegenerative diseases, Parkinson's is the second most common disease. Although several medications are available in the market, this disease still remains incurable and only the symptoms are controlled to a certain extent with severe side effects. For these reasons we decided to search for a novel therapeutic measure. The objective of this publication was to find a therapeutic procedure to cure this devastating disease. In this study, a biocompatible, easily permeable, cationic nanoparticle-layered double hydroxide was synthesized. Within the layers of these nanoparticles we intercalated α synuclein siRNA, which helps to silence the α synuclein gene. After the intercalation, which was optimized at a 1 : 40 ratio of siRNA : (LDH), we studied its stability in blood by a RNase protection test and serum protection assay. Both proved that LDH was an excellent nanocarrier that can protect intercalated molecules within its layers. After that, several cellular studies were performed by FACS to evaluate its biocompatibility after intercalation and cellular internalization. Results of the biocompatibility studies found it to be nontoxic and in the cellular internalization study, 51.55% of cells were taken into the nanoconjugate and confocal microscopy supported the data from FACS. Lastly, ELISA was performed to discover protein levels in the control, overexpressed, and treated groups of the SH-SY5Y cell line. These results verified that this nanoconjugate is a protective treatment procedure for Parkinson's disease.

Facile synthesis of carbon fiber reinforced polymer-hydroxyapatite ternary composite: A mechanically strong bioactive bone graft.

Carbon fiber reinforced carboxymethyl cellulose-hydroxyapatite ternary composites have been synthesized by a simple wet precipitation method for weight bearing orthopedic application. Composites were synthesized with the incorporation of chemically functionalized carbon fibers. The functional groups onto the surface of fibers induced the formation of hydroxyapatite at the bridging position through which fibers were effectively bound with matrix. Consequently, the flexural strength and compressive strength of composite have reached to 140 MPa and 118 MPa, respectively. The flexural modulus of the composite is in the range of 9-22 GPa. In-vitro cell study showed that the composite possesses excellent cell proliferation and differentiation ability. With these excellent mechanical and biological properties, synthesized composite exhibits potential to be used as a mechanically compatible bioactive bone graft.

One pot synthesis of carbon dots decorated carboxymethyl cellulose- hydroxyapatite nanocomposite for drug delivery, tissue engineering and Fe3+ ion sensing.

In this work, carbon dots conjugated carboxymethyl cellulose-hydroxyapatite nanocomposite has been synthesized by one-pot synthesis method and used for multiple applications like metal ion sensing, osteogenic activity, bio-imaging and drug carrier. The structure and morphology of the nanocomposite were systematically characterized by FTIR, XRD, TGA, FESEM, TEM and DLS. Results clearly demonstrated the formation of fluorescent enabled carbon dots conjugated nanocomposite from carboxymethyl cellulose-hydroxyapatite nanocomposite by a simple thermal treatment. The synthesized nanocomposite is smaller than 100 nm and exhibits fluorescence emission band around 440 nm upon excitation with 340 nm wavelength. In the meantime, the nanocomposite was loaded with a chemotherapeutic drug, doxorubicin to evaluate the drug loading potential of synthesized nanocomposite. Moreover, the as-synthesized nanocomposite showed good osteogenic properties for bone tissue engineering and also exhibited excellent selectivity and sensitivity towards Fe3+ ions.

siRNA-nanoparticle conjugate in gene silencing: A future cure to deadly diseases?

Alzheimers, cancer, acquired immune deficiency syndrome (AIDS) are considered to be some of the most deadly diseases of the 21st century on account of their severity and rapid increase in the number of affected population and with scarce cases of recovery, they still remain a troubling paradox. Specifically, with millions of cancer patients worldwide and lack of proper cure for the same, understanding the deadly disease at the molecular level and planning a therapeutic strategy in the same line is the need of the hour. Further, the potential threat of prevalence and escalation of Alzheimer's and HIV (human immunodeficiency virus) infection by more than three times as of recent past, needs a medical breakthrough to arrive at a meaningful solution to tackle the present day scenario. It is evident that these diseases initiate and propagate based on certain genes and their expression which needs to be silenced by the help of small interfering RNA (siRNA) by at least 70%. For short term silencing of the protein coding genes, siRNA is the most appropriate tool. Hence, the present communication explores the possibility for treatment and cure of a plethora of deadly diseases, e.g., cancer, including Alzheimer's and AIDS to some extent, emphatically at the molecular level, using the current trend of RNAi (RNA interference) delivery via a wide variety of nanoparticles.

In vivo pharmacological evaluation and efficacy study of methotrexate-encapsulated polymer-coated layered double hydroxide nanoparticles for possible application in the treatment of osteosarcoma.

Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD50) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.

Mg-Al layered double hydroxide-methotrexate nanohybrid drug delivery system: evaluation of efficacy.

Mg-Al layered double hydroxide nanoparticles were synthesized by one-pot co-precipitation method and anticancerous drug methotrexate was incorporated into it by in-situ ion exchange. The LDH-MTX nanohybrid produced moderately stable suspension in water, as predicted by zeta potential measurement. X-ray diffraction revealed that the basal spacing increased to nearly twice the same for pristine LDH on MTX intercalation. Thermogravimetric analyses confirmed an increase in thermal stability of the intercalated drug in the LDH framework. A striking enhancement in efficacy/sensitivity of MTX on the HCT-116 cells was obtained when intercalated within the LDH layers, as revealed by the attainment of half maximal inhibitory concentration of LDH-MTX nanohybrid by 48 h, whereas, bare MTX required 72 h for the same. The MTX release from MgAl-LDH-MTX hybrids in phosphate buffer saline at pH7.4 followed a relatively slow, first order kinetics and was complete within 8 days following diffusion and crystal dissolution mechanism.

Comparative assessment of structural and biological properties of biomimetically coated hydroxyapatite on alumina (alpha-Al2O3) and titanium (Ti-6Al-4V) alloy substrates.

Previous reports have shown the use of hydroxyapatite (HAp) and related calcium phosphate coatings on metal and nonmetal substrates for preparing tissue-engineering scaffolds, especially for osteogenic differentiation. These studies have revealed that the structural properties of coated substrates are dependent significantly on the method and conditions used for coating and also whether the substrates had been modified prior to the coating. In this article, we have done a comparative evaluation of the structural features of the HAp coatings, prepared by using simulated body fluid (SBF) at 25 degrees C for various time periods, on a nonporous metal substrate titanium-aluminium-vanadium (Ti-6Al-4V) alloy and a bioinert ceramic substrate alpha-alumina (alpha-Al(2)O(3)), with and without their prior treatment with the globular protein bovine serum albumin (BSA). Our analysis of these substrates by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectrometry showed significant and consistent differences in the quantitative and qualitative properties of the coatings. Interestingly, the bioactivity of these substrates in terms of supporting in vitro cell adhesion and spreading, and in vivo effects of implanted substrates, showed a predictable pattern, thus indicating that some coated substrates prepared under our conditions could be more suitable for biological/biomedical applications.

Self-assembled structures of hydroxyapatite in the biomimetic coating on a bioinert ceramic substrate.

The tribological properties of alumina ceramic are excellent due in part to a high wettability because of the hydrophilic surface and fluid film lubrication that minimizes the adhesive wear. Such surfaces are further modified with bioactive glass/ceramic coating to promote direct bone apposition in orthopedic applications. The present communication reports the biomimetic coating of calcium hydroxyapatite (HAp) on dense (2-3% porosity) alumina (alpha-Al(2)O(3)) substrate (1cm x 1cm x 0.5 cm), at 37 degrees C. After a total period of 6 days immersion in simulated body fluid (SBF), at 37 degrees C, linear self-assembled porous (pore size: approximately 0.2 microm) structures (length: approximately 375.39 microm and width: 5-6 microm) of HAp were obtained. The phenomenon has been demonstrated by self-assembly and diffusion-limited aggregation (DLA) principles. Structural and compositional characterization of the coating was carried out using SEM with EDX facility, XRD and FT-IR data.