Aqif Anwar Chaudhry

Instant nano-hydroxyapatite: a continuous and rapid hydrothermal synthesis

Nano-particle hydroxyapatite (HA) rods, were rapidly synthesised using a three pump continuous hydrothermal process (using a water feed at up to 400 degrees C and at 24 MPa): the product was obtained as a highly crystalline and phase pure material, without the need for an ageing step or subsequent heat treatment.

Synthesis and characterisation of magnesium substituted calcium phosphate bioceramic nanoparticles made via continuous hydrothermal flow synthesis

Continuous hydrothermal flow synthesis (CHFS) technology has been used as an efficient and direct route to produce a range of largely crystalline magnesium substituted calcium phosphate bioceramics. Initially, magnesium substituted hydroxyapatite, Mg-HA, according to the formula [Ca10−xMgx(PO4)6(OH)2] was prepared in the CHFS system for x = 0.2 [where x:(10 − x) is the Mg:Ca ratio used in the reagents]. Biphasic mixtures of Mg-HA and Mg-whitlockite were obtained corresponding to x values in the range x = 0.4–1.6. The direct synthesis of phase pure crystalline Mg-whitlockite [based on the formula (Ca3−yMgy(HPO4)z(PO4)2−2z/3] was also achieved using the CHFS system for the range y = 0.7–1.6 (this corresponds to the range x = 1.6–5.3). With increasing substitution of magnesium for calcium, the material became ever more amorphous and the BET surface area generally increased. All the as-precipitated powders (without any additional heat treatments) were analyzed using techniques including X-ray powder diffraction, Raman spectroscopy and Fourier transform infra-red spectroscopy. Transmission electron microscopy (TEM) images revealed that in the case of y = 1.2, the Mg-whitlockite material comprised of ca. 28 nm sized spheres. The use of the CHFS system in this context facilitated rapid production of combinations of particle properties (crystallinity, size, shape) that were hitherto unobtainable in a single step process.

High-strength nanograined and translucent hydroxyapatite monoliths via continuous hydrothermal synthesis and optimized spark plasma sintering

The synthesis of high-strength, completely dense nanograined hydroxyapatite (bioceramic) monoliths is a challenge as high temperatures or long sintering times are often required. In this study, nanorods of hydroxyapatite (HA) and calcium-deficient HA (made using a novel continuous hydrothermal flow synthesis method) were consolidated using spark plasma sintering (SPS) up to full theoretical density in ∼5 min at temperatures up to 1000°C. After significant optimization of the SPS heating and loading cycles, fully dense HA discs were obtained which were translucent, suggesting very high densities. Significantly high three-point flexural strength values for such materials (up to 158 MPa) were measured. Freeze-fracturing of disks followed by scanning electron microscopy investigation revealed selected samples possessed sub-200 nm sized grains and no visible pores, suggesting they were fully dense.

Raman Spectroscopy of Natural Bone and Synthetic Apatites

Abstract Raman spectroscopy of natural bones and hydroxyapatites is described. In addition, how Raman spectroscopy has proved crucial in providing baseline data for the modification of synthetic apatite powders that are routinely used now as bone replacement materials is explained. It is important to understand the chemical structural properties of natural bone. Bone consists of two primary components: an inorganic or mineral phase, which is mainly a carbonated form of a nanoscale crystalline calcium phosphate, closely resembling hydroxyapatite, and an organic phase, which is composed largely of type I collagen fibers. Other constituents of bone tissue include water and organic molecules such as glycosaminoglycans, glycoproteins, lipids, and peptides. Ions such as sodium, magnesium, fluoride, and citrate are also present, as well as hydrogenophosphate. Hence, the mineral phase in bone may be characterized essentially as nonstoichiometric substituted apatite. Such a distinction is important in the development of synthetic calcium phosphates for application as skeletal implants. An understanding of bone function and its interfacial relationship to an implant clearly depends on the associated structure and composition. Therefore, it is essential to fully understand the chemical composition of bone, and Raman spectroscopy is an excellent technique for such an analysis.

Gold nanoparticle decorated single walled carbon nanotube nanocomposite with synergistic peroxidase like activity for D-alanine detection

In this report, a gold nanoparticle decorated single walled carbon nanotube (SWCNTs) nanocomposite was shown to possess synergistic intrinsic peroxidase like activity and enhanced affinity towards H2O2 oxidation. The gold nanoparticle decorated SWCNTs nanocomposite was characterized by high catalytic activity, enhanced stability from the gold nanoparticles and improved dispersion from the SWCNTs. Subsequently, this nanocomposite was proved to be a novel peroxidase mimetic with great potential to catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2 to yield a blue colored product. As a proof of concept, the gold nanoparticle decorated SWCNTs composite was used as a robust nanoprobe for the detection of D-alanine with improved analytical characteristics. Taking into account the valuable intrinsic peroxidase activity of the nanohybrid, the present work may find widespread applications in the field of sensors and biosensors for diverse applications.

Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration

Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration.

Triethyl orthoformate mediated a novel crosslinking method for the preparation of hydrogels for tissue engineering applications: characterization and in vitro cytocompatibility analysis

This paper describes the development of a new crosslinking method for the synthesis of novel hydrogel films from chitosan and PVA for potential use in various biomedical applications. These hydrogel membranes were synthesized by blending different ratios of chitosan (CS) and poly(vinyl alcohol) (PVA) solutions and were crosslinked with 2.5% (w/v) triethyl orthoformate (TEOF) in the presence of 17% (w/v) sulfuric acid. The physical/chemical interactions and the presence of specific functional groups in the synthesized materials were evaluated by Fourier transform infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). Thermal gravimetric analysis (TGA) proved that these crosslinked hydrogel films have good thermal stability which was decreased as the CS ratio was increased. Differential scanning calorimetry (DSC) exhibited that CS and PVA were present in the amorphous form. The solution absorption properties were performed in phosphate buffer saline (PBS) solution of pH7.4. The 20% PVA-80% CS crosslinked hydrogel films showed a greater degree of solution absorption (183%) as compared to other compositions. The hydrogels with greater CS concentration (60% and 80%) demonstrated relatively more porous structure, better cell viability and proliferation and also revealed good blood clotting ability even after crosslinking. Based on the observed facts these hydrogels can be tailored for their potential utilization in wound healing and skin tissue engineering applications.

Rapid hydrothermal flow synthesis and characterisation of carbonate- and silicate-substituted calcium phosphates.

A range of crystalline and nano-sized carbonate- and silicate-substituted hydroxyapatite has been successfully produced by using continuous hydrothermal flow synthesis technology. Ion-substituted calcium phosphates are better candidates for bone replacement applications (due to improved bioactivity) as compared to phase-pure hydroxyapatite. Urea was used as a carbonate source for synthesising phase pure carbonated hydroxyapatite (CO3-HA) with ≈5 wt% substituted carbonate content (sample 7.5CO3-HA) and it was found that a further increase in urea concentration in solution resulted in biphasic mixtures of carbonate-substituted hydroxyapatite and calcium carbonate. Transmission electron microscopy images revealed that the particle size of hydroxyapatite decreased with increasing urea concentration. Energy-dispersive X-ray spectroscopy result revealed a calcium deficient apatite with Ca:P molar ratio of 1.45 (±0.04) in sample 7.5CO3-HA. For silicate-substituted hydroxyapatite (SiO4-HA) silicon acetate was used as a silicate ion source. It was observed that a substitution threshold of ∼1.1 wt% exists for synthesis of SiO4-HA in the continuous hydrothermal flow synthesis system, which could be due to the decreasing yields with progressive increase in silicon acetate concentration. All the as-precipitated powders (without any additional heat treatments) were analysed using techniques including Transmission electron microscopy, X-ray powder diffraction, Differential scanning calorimetry, Thermogravimetric analysis, Raman spectroscopy and Fourier transform infrared spectroscopy.

A new synthetic methodology for the preparation of biocompatible and organo-soluble barbituric- and thiobarbituric acid based chitosan derivatives for biomedical applications

Chitosans poor solubility especially in organic solvents limits its use with other organo-soluble polymers; however such combinations are highly required to tailor their properties for specific biomedical applications. This paper describes the development of a new synthetic methodology for the synthesis of organo-soluble chitosan derivatives. These derivatives were synthesized from chitosan (CS), triethyl orthoformate and barbituric or thiobarbituric acid in the presence of 2-butannol. The chemical interactions and new functional motifs in the synthesized CS derivatives were evaluated by FTIR, DSC/TGA, UV/VIS, XRD and (1)H NMR spectroscopy. A cytotoxicity investigation for these materials was performed by cell culture method using VERO cell line and all the synthesized derivatives were found to be non-toxic. The solubility analysis showed that these derivatives were readily soluble in organic solvents including DMSO and DMF. Their potential to use with organo-soluble commercially available polymers was exploited by electrospinning; the synthesized derivatives in combination with polycaprolactone delivered nanofibrous membranes.

Production of chitosan PVA PCL hydrogels to bind heparin and induce angiogenesis

ABSTRACT New blood vessel formation is an essential part of wound healing to provide cells with the nutrients and oxygen for their survival. Many nonhealing ulcers fail to heal because of poor blood supply and skin grafts will also fail to take on poorly vascularized wound beds. There is a real need for proangiogenic biomaterials to assist wound healing. In vivo heparin binds proangiogenic growth factors and helps regulate new blood vessel formation, hence heparin containing biomaterials are attractive. To achieve a hydrogel with high heparin binding capacity a composite of chitosan, poly(vinyl alcohol) (PVA) and polycaprolactone (PCL) was produced. Chitosan is a biodegradable natural polymer with great potential for biomedical applications due to its biocompatibility, high charge density and nontoxicity. PVA is biocompatible and nontoxic with good chemical stability, film-forming ability, and high hydrophilicity. PCL has physicochemical and mechanical properties comparable to those of the biological tissues and due its hydrophilic nature helps in the sustained release of drugs. Accordingly in this study we explored a range of PCL concentrations from 4% to 16% added to hydrogels composed of chitosan and PVA. Heparin was blended into the polymer mixture and the nanoporous structure was created by freeze-drying the PCL hydrogel. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR) and XPS confirmed the presence of sulfur on the surface of the hydrogels. Their porous morphology was investigated by scanning electron microscope (SEM). The Chick Chorionic Allantoic Membrane (CAM) assay was used to study the angiogenic potential of these materials and histology (H&E and Goldner trochome) was used to confirm the presence of new blood vessels inside the hydrogels. We report that the addition of 8% PCL to the hydrogels gave porous structures containing heparin, which significantly increased new blood vessel formation into the hydrogels. These hydrogels offer a new approach to biomaterials, which could be added to wounds to improve vascularization. GRAPHICAL ABSTRACT