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Development of biomaterials supporting angiogenesis are highly desired in medical applications. In current work, chitosan and cellulose were cross-linked by using triethyl orthoformate and loaded with sulfur-doped titanium oxide nanoparticles. A readily available and inexpensive titanium oxide was added as a potential proangiogenic agent based on our group findings and other reports on metal oxide nanoparticles activity to stimulate angiogenesis. A simple freeze gelation method led to the development of flexible, foldable, and porous membranes. To investigate the chemical characteristics of the synthesized membranes, Fourier-transform infrared spectroscopy was used. Scanning electron microscopy equipped with energy-dispersive X-ray microanalysis was employed for surface morphological investigations. The cross-linked membranes showed higher degree of swelling capacity compared to the same material with titania-loaded nanoparticles in vitro. The synthesized materials showed higher degree of degradation in H2 O2 as compared to phosphate-buffered saline and lysozyme. Chorioallantoic membrane assay was done to investigate the angiogenic potential. Titanium oxide nanoparticles loaded membranes (CLHTS-5 wt%) exhibited the best degree of angiogenesis in comparison to the other tested materials. In CLHTS-5 wt% experimental group, a good level of attachment and ingrowth of several blood vessels was observed. Interestingly, the same tested group (CLHTS-5 wt%) had shown the increasing trend of cellular metabolic rate of the seeded cells from Day 0 to Day 7 in vitro. These findings were further confirmed by the decline in lactate dehydrogenase enzyme release which was monitored until 72 h, indicating the promising ability of this biomaterial in wound healing applications.

Scar free healing together with pain management is one of the major considerations in full thickness wound healing. Extensive wounds take longer to heal without any clinical intervention and, hence, need natural or artificial extracellular matrix support for quick skin regeneration. To address these issues, medicated 3D porous biomimetic scaffolds were developed with a unique combination of biopolymers, that is, chitosan, sodium alginate, and elastin, supplemented with a non-steroidal anti-inflammatory drug (NSAID). Scaffolds were physically characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, and degradation studies. Findings of the performed analyses proved that these skin substitutes suitable for skin tissue engineering applications attributable to their nano-microporous structures (pore size in range of 0.085-256 μm) allowing cell infiltration and high-water absorption capacity for management of wound exudates. Optimal dose of the loaded ibuprofen was estimated by evaluating effect of variable concentrations of ibuprofen (control, ILM-10, ILM-15, and ILM-20) on adipose tissue-derived mesenchymal stem cells (ASCs) proliferation rate. Out of all experimental groups, ILM-20 constructs were found to accelerate the proliferation rate of seeded ASCs confirming their non-cytotoxic characteristics as well potential to be used for translational scaffold-based therapies.

Chitosan/collagen-based hydrogels were studied for their promising role in skin tissue engineering applications due to their unique biocompatibility and biodegradation properties. Amino acids are not only the mean of protein building units but also support endothelial cells proliferation and trigger angiogenesis during wound healing. The purpose of this study was to prepare amino acid based pro-angiogenic materials. Three structurally closed amino acids (AA) (arginine, alanine and phenylalanine) were loaded into chitosan/collagen hydrogels (ACC hydrogels) to study their effect on angiogenesis. In this study the ACC hydrogels were prepared through freeze drying procedure and their angiogenic potential was studied by chorioallantoic membrane assay (CAM assay). FTIR analysis was performed to confirm that there was no chemical change took place in polymeric materials during synthesis procedures. Results revealed that, arginine-loaded hydrogels were the most porous, with more interconnected pores and also the maximum growth of blood vessels were found around and inside the arginine loaded scaffold. The qualitative analysis for blood vessels showed the significant difference between control, chitosan/collagen alanine loaded hydrogel (CH-Ala), chitosan/collagen phenylalanine loaded hydrogel (CH-Phe) and chitosan/collagen arginine loaded hydrogel (CH-Arg) materials. Among these studied materials the CH-Arg was found more capable for angiogenesis.

In the current study, boric acid loaded chitosan (CS) and collagen-based hydrogels were prepared. Hydrogels with four different boric acid concentrations were prepared; control hydrogel (wi...

Alveolar bone loss is associated with infections and its augmentation is a pre-requisite for the success of dental implants. In present study, we aim to develop and evaluate novel freeze dried doxycycline loaded chitosan (CS)/hydroxyapatite (HA) spongy scaffolds where hydroxypropylmethyl cellulose (HPMC) was added as a crosslinker. Scaffolds displayed compressive strength of 14MPa/cm3 and 0.34 as elastic response. The interconnected pore diameter was 41-273μm, favorably provided the template supporting cells and transport. An overall 10% degradation was seen after 14day's studies at pH 7.4 in PBS. Doxycycline hyclate, a frequently used drug to counter oral infections, demonstrated an initial burst release (6-8h), followed by a sustain release profile for the remaining 64h. CS/HA/HPMC scaffolds were nontoxic and promoted pre-osteoblast cell viability as seen with live/dead calcein staining after 24h where scaffolds with 10% and 25% HPMC by weight of scaffold had more viable cells. Scaffolds with 10%, 20% and 25% HPMC by weight of scaffold showed efficient cellular adhesion as seen in scanning electron microscopy images (day 8) indicating that pre-osteoblast cells were able to adhere well on the surface and into the porous structure via cytoplasmic extensions. Hoechst 33258 nuclear staining at day 2 and 8 indicated cell proliferation which was further supported byMTT assay at day 2, 4 and 8. Although all scaffolds supported pre-osteoblast cell viability, alkaline phosphatase (ALP) staining demonstrated that upon induction, differentiation was pronounced in case of scaffolds with 10% HMPC scaffolds. Conclusively, these materials having all the required mechanical and biological properties are potential candidates for alveolar bone regeneration.

The aim was to synthesize bioactive electrospun fibers for biomedical and dental application with improved biocompatibility. In situ precipitation of nano-hydroxyapatite (nHA) was performed with various concentrations (0.5%, 1%, 2%, 3%, and 5% wt/wt) of functionalized multi-walled-carbon nanotubes (MWCNTs) by using microwave irradiation technique. The obtained composites were characterized by Fourier Transform Infrared (FTIR), X-ray Diffraction (XRD), Thermogravimetric Analysis/Differential Scanning Calorimetry (TGA/DSC), and the cylindrical discs were made for mechanical testing. The failure behavior was analyzed by Scanning Electron Microscope (SEM). CNT and HA/CNT were silanized with γ-methacryloxypropyl-trimethoxysilane (MPTS) and mixed with polyvinyl alcohol (10% wt./vol.) and electrospun to fabricate fibers. The biocompatibility of both fibers was accessed by their effects on angiogenesis in a chick chorioallantoic membrane (CAM) assay. The electrospun fibers were analyzed by SEM. FTIR confirmed the structural behavior of pre and post-silanized HA/CNT. XRD showed the phase purity and crystallinity before and after heat treatment. Mechanical properties showed that 3% loaded HA/CNT has higher compressive strength (100.5±5.9MPa) compared to others and the failure behavior exhibited dispersion of CNT in HA matrix. The HA/CNT electrospun fibers showed significantly more blood vessels formation compared to CNT fibers. These HA/CNT electrospun fibers showed promising results in terms of biocompatibility and with improved mechanical properties of CNT reinforced composites, they can be used in load bearing clinical applications.

Angiogenesis is a process of formation of new small blood vessels from existing vessels and is very critical for proper and rapid tissue healing. As reactive oxygen species (ROS) are known for their ability to promote angiogenesis, in this study zinc oxide (ZnO) and zinc peroxide (ZnO2) nano-particles (NP's) encapsulated chitosan (CS) and cellulose based hydrogels were synthesized. ZnO2 is comparatively stronger oxidizing agent as compared to ZnO, therefore, in this study it was hypothesized that ZnO2 would deliver better angiogenic potential than ZnO. Three types of hydrogels were prepared; control hydrogel (without nano-particles), hydrogel having ZnO NP's and hydrogel having ZnO2 NP's. The hydrogels were characterized by scanning electron microscopy (SEM) for structural morphology, Fourier transform infrared spectroscopy (FTIR) for chemical functional groups analyses and X-ray Diffraction (XRD) to investigate the crystalline or amorphous structure of NP's. The solution absorption capacity was tested in PBS and degradation was investigated in PBS, PBS/H2O2 and PBS/lysozyme solutions. The angiogenic behavior of these materials was studied in chorioallantoic membrane (CAM) assay and ZnO2 based material showed significant higher angiogenesis. Keywords: Angiogenesis, Chorioallantoic membrane assay, Zinc oxide nanoparticles, Zinc peroxide nanoparticles, Reactive oxygen species

Novel cefixime loaded chitosan/HA/Nylon 6 electropsun mats were prepared with excellent swelling properties and were tested for cell attachment and cell proliferation. FTIR spectra shows that hydrogen bonding is developed between composite fibers, as pronounced shape change could be seen in amide I and II peaks. SEM analysis displayed completely different morphology (fiber diameters, general appearance, pore-size and shape) of composite fibers as compared to N6 fibers. Composite fibers showed high thermal stability in thermal gravimetric analysis. The ultimate tensile strength of fiber films was around 4.45 MPa. Both composite and Nylon 6 fibers demonstrated sustained drug release up to 24 h. Although the composite and control (Nylon 6) fibers, both, provided compatible favorable environment for the osteoblast cells, the composite fibers provided a better suited environment for the osteoblast cells differentiation and in parallel supporting cellular population also composite fibers exhibited superior swelling properties than the control which in turn complement the healing properties of wound dressings.

The development of biologically active molecules based on molecular recognition is an attractive and challenging task in medicinal chemistry and the molecules that can activate/deactivate certain receptors are of great medical interest. In this contribution, selected pyrimidine/piperidine derivatives were synthesized and tested for the ability to activate/deactivate Aryl hydrocarbon receptor (AhR) and Glucocorticoid receptor (GR). Tested compounds are shown to activate the receptors but to much lesser extent than positive controls, dioxin and dexamethasone for Ahr and GR, respectively. However, some of them antagonized the positive controls action. Although further in vivo studies are needed to fully characterize the bioactivities of these compounds, the reported in vitro evidences demonstrate that they might be used as the modulators of AhR and GR activities.

This research paper demonstrates efficacy of chitosan and thyroxine loaded chitosan (CS) dressings for their angiogenic and wound healing potential. The dressings were prepared by freeze gelation method. Thyroxine was loaded by physical adsorption into chitosan membranes. The porosity was analyzed by scanning electron microscopy (SEM) and chemical structures were investigated by Fourier transform infra-red spectroscopy (FTIR). Cell culture studies showed materials were non-toxic and chorioallantoic membranes assay (CAM) confirmed that the thyroxine loaded chitosan stimulated angiogenesis much higher than simple chitosan dressings. In addition, thyroxine loaded dressings showed excellent wound healing potential when tested on full thickness rats wounds. A good epithelialization was obtained along with robust wound closure. Overall, as compared to chitosan, thyroxine containing membranes showed high level of angiogenesis and fast wound healing.

Angiogenesis is one of the most important processes in repair and regeneration of many tissues and organs. Blood vessel formation also play a major role in repair of dental tissue(s) after ailments like periodontitis. Here we report the preparation of chitosan/carboxymethyl cellulose/hydroxyapatite based hydrogels, loaded with variable concentrations of thyroxin i.e., 0.1 μg/ml, 0.5 μg/ml and 1 μg/ml. Scanning electron microcopy images (SEM) showed all hydrogels were found to be porous and solution absorption study exhibited high swelling potential in aqueous media. FTIR spectra confirmed that the used materials did not change their chemical identity in synthesized hydrogels. The synthesized hydrogels demonstrated good bending, folding, rolling and stretching abilities. The hydrogels were tested in chick chorioallantoic membrane (CAM) assay to investigate their angiogenic potential. Hydrogel containing 0.1 μg/ml of thyroxine showed maximum neovascularization. For cytotoxicity analyses, preosteoblast cells (MC3T3-E1) were seeded on these hydrogels and materials were found to be non-toxic. These hydrogels with pro-angiogenic activity possess great potential to be used for periodontal regeneration.

The success of wound healing depends upon the proper growth of vascular system in time in the damaged tissues. Poor blood supply to wounded tissues or tissue engineered grafts leads to the failure of wound healing or rejection of grafts. In present paper, we report the synthesis of novel organosoluble and pro-angiogenic chitosan derivative (CSD) by the reaction of chitosan with 1,3-dimethylbarbituric acid and triethylorthoformate (TEOF). The synthesized material was characterized by FTIR and 13C-NMR to confirm the incorporated functional groups and new covalent connectivities. Biodegradability of the synthesized chitosan derivative was tested in the presence of lysozyme and was found to be comparable with CS. The cytotoxicity and apoptosis effect of new derivative was determined against gastric adenocarcinoma (AGS) cells and was found to be non-toxic. The CSD was found to be soluble in majority of organic solvents. It was blended with polycaprolactone (PCL) to form composite scaffolds. From an ex ovo CAM assay, it was noted that CSD stimulated the angiogenesis.

Periodontal disease is associated with the destruction of periodontal tissues, along with other disorders/problems including inflammation of tissues and severe pain. This paper reports the synthesis of meloxicam (MX) immobilized biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) based electrospun (e-spun) fibers and films. Electrospinning was employed to produce drug loaded fibrous mats, whereas films were generated by solvent casting method. In-vitro drug release from materials containing varying concentrations of MX revealed that the scaffolds containing higher amount of drug showed comparatively faster release. During initial first few hours fast release was noted from membranes and films; however after around 5h sustained release was achieved. The hydrogels showed good swelling property, which is highly desired for soft tissue engineered implants. To investigate the biocompatibility of our synthesized materials, VERO cells (epithelial cells) were selected and cell culture results showed that these all materials were non-cytotoxic and also these cells were very well proliferated on these synthesized scaffolds. These properties along with the anti-inflammatory potential of our fabricated materials suggest their effective utilization in periodontital treatments.

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 tissu...

With an increase in the demand for skin regeneration products, there is a noticeable increase in developing materials that encourage, wound healing and skin regeneration. It has been reported that antioxidants play an important role in anti-inflammatory reactions, cellular proliferation and remodeling phase of wound healing. While consideration all these factors, a novel α-tocopherol acetate (vitamin E) (VE) loaded bi-layered electrospun membrane, based on lower polycaprolactone (PCL) layer and upper polylactic acid (PLA) layer, was fabricated through electrospinning. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), in-vitro degradation studies, swelling studies and VE release studies were performed to evaluate structural, physical and in-vitro behavior of membranes. Biological properties of membranes were evaluated through cell proliferation assay, cell adhesion studies, live/dead cell assay and CAM assay. SEM images showed that the average diameter of nanofibers ranged from 1 to 6 μm, while addition of VE changed the diameter and morphology of fibers. Bi-layered membranes showed significant swelling behavior through water uptake, membranes loaded with 30% VE showed 8.7% and 6.8% degradation in lysozyme and H2O2 respectively. 20% and 30% VE loaded membranes followed Korsmeyer-Peppas and first order drug release kinetics followed by non-fickian drug release kinetics. Membranes showed non-toxic behavior and supported cell proliferation via alamar blue assay, cell adhesion via SEM, cell viability via live/dead assay and wound healing by scratch assay. CAM assay showed that membranes having VE supported angiogenesis and showed significant formation of blood vessels making it suitable for skin regeneration and wound healing. Results showed that large surface area of nanofibers, porous structure and biocompatible nature are suitable for targeted clinical applications.

Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a–3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a–3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC50 values were found in the range of 61.98 ± 0.43 to 273.43 ± 0.96 μM and 7-Deazaxanthine was taken as a standard inhibitor with IC50 = 38.68 ± 4.42 μM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a–4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b–4g exhibited a good inhibitory potential in the range of 43.86 ± 1.11–163.43 ± 2.03 μM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.

Nanoparticles are well recognized for their biological applications including tissue-regeneration due to large surface area and chemical properties. In this study, K-doped zinc oxide (ZnO) nanoparticles containing porous hydrogels were synthesized via freeze gelation. The morphology and pore dimensions were studied by scanning electron microscopy (SEM). The chemical structural analysis of the synthesized hydrogels was investigated by Fourier Transform Infrared (FTIR) spectroscopy. In swelling studies, material containing ZnO nanoparticles with 2% potassium dopant concentration CLH-K2.0) showed greater degree of swelling as compared to all other materials. The degradation studied was tested in three different degradation media, i.e. phosphate buffer saline (PBS), lysozyme and hydrogen peroxide and relatively higher degradation was seen in hydrogen peroxide. The synthesized hydrogels were implanted on the chick chorioallantoic membrane (CAM) to investigate their angiogenic potential. The CLH-K2.0 hydrogel stimulated angiogenesis greater than all other materials; blood vessels were attached and grown inside this scaffold, showing its strong angiogenic potential.

This article presents an (hydroxypropyl)methylcellulose (HPMC) mediated synthesis of highly porous scaffolds containing nanocrystalline hydroxyapatite (n-HAp) and chitosan (CS) as major inorganic and organic phases, respectively. A mixture of n-HAp, CS, and HPMC is homogenized and freeze-dried to yield n-HAp/CS/HPMC composite scaffolds closely emulating trabecular bone in density (0.02 g cm-3) and porosity (89%). SEM images substantiate the porous structure of the scaffolds (pore size: 100-300 μm). The mechanical analysis reveal excellent compressive strength of the porous n-HAp/CS/HPMC scaffold (9.65 MPa) that is also comparable with human trabecular bone. The in vitro bioactivity and degradability of the porous scaffolds are investigated in tris-HCl-buffered synthetic body fluid (SBF) and phosphate buffer solution (PBS), respectively. The results indicate a rapid increase in scaffold mass due to apatite-like deposition and good resorbability. The SEM images of SBF soaked samples demonstrate apatite-like deposition on the surface of scaffolds with Ca/P ratio of 1.63 after 7 days of soaking in SBF. These results suggest that porous n-HAp/CS/HPMC scaffolds, due to their structural similarity, mechanical and in vitro biological properties, can become useful alternatives for trabecular bone regeneration and repair. © 2015 by American Scientific Publishers.

Vascular endothelial growth factor (VEGF) stimulates endothelial cells to migrate, proliferate and form new blood vessels. However direct delivery of VEGF has not become clinically adopted as a means of stimulating blood vessel formation and wound healing because of its relatively poor stability and its production of immature blood vessels. A simpler way of stimulating production of VEGF in situ is explored in this study following reports of deoxy sugars involved in inducing VEGF production. The pro-angiogenic effect of L and D isomers of deoxy sugars (ribose, fucose and rhamnose) loaded into biodegradable chitosan/collagen hydrogels was examined using a chick chorionic allantoic membrane assay. The L-sugars were all pro-angiogenic but only the 2-deoxy-D-ribose had strong effects on angiogenesis. Furthermore, these sugars could not be metabolised by four strains of Staphylococcus aureus, as a metabolic substrate for growth, although some of these could be metabolised by another typical pathogen, Pseudomonas aeruginosa. The effects of 2-deoxy-D-ribose in a chitosan/collagen hydrogel on wound healing were also assessed. This biomaterial doubled the rate of cutaneous wound healing in rats associated with an increase in vascularisation detected by staining for CD34 positive cells.

In this study, an effective, biocompatible and biodegradable co-polymer comprising of chitosan (CS) and polyvinyl alcohol (PVA) hydrogels, chemically crosslinked and impregnated with doxazocin, is reported. The chemical structural properties of the hydrogels were evaluated by Fourier Transform Infrared spectroscopy (FTIR) and physical properties were analysed by scanning electron microscopy (SEM). The swelling behaviour is an important parameter for drug release mechanism and was investigated to find out the solution absorption capacity of the synthesized hydrogels. MTT assay revealed that doxazocin loaded hydrogels significantly hindered the cell viability. Flow cytometry analysis was performed to analyse the effect of 8CLH and 4CLH on regulation of cell cycle. Moreover, in vivo anti-cancer potential of synthesized hydrogels was assessed by CAM Assay. Results displayed that 8CLH with 1 mg/ml of doxazocin had prominently decreased the angiogenesis and significantly increased the number of cells in G1 phase of cell cycle. These results declared that 8CLH will be a good addition among hydrogels used for treatment of cancer by onsite delivery of drug.

Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer’s disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the tested compounds exhibited inhibitory activity against AChE and BChE. Among them 4f and 6e showed the highest AChE inhibitory activity with IC50 91.21±0.06 and 68.52±0.04 μM, respectively. However compound 5a exhibited the highest inhibitory activity against BChE (IC50 55.21±0.12 μM).

In era of modern disposable and bendable energy storage technology, flexible and environmentally safe electrodes are extremely feasible. This study elaborates the synthesis of highly flexible and stretchable polymer gel membrane by covalently cross linking of chitosan (CS) and poly vinyl alcohol (PVA) immobilized MnO2 for efficient, light-weight and cost-effective energy storage technologies. Fourier transform infrared spectroscopy (FTIR) revealed the existence of CS/PVA as well as MnO2 in original form without any chemical change. 3-dimensional morphology including porosity of the presented fabricated membranes are examined by scanning electron microscopy (SEM). Presented CS/PVA based MnO2 membranes were bendable and can be cut in any shape by the simple usage of scissor to employ by means of working electrode. Furthermore, electrochemical behaviour was tested by cyclic voltammetry (CV) and Galvanostatic charge/discharge (GCD) measurements in neutral/acidic electrolytes. CS/PVA based MnO2 membranes showed excellent capacitive behaviour with specific capacitance of ~140 F g−1. GCD measurements also verified efficient kinetics of charging/discharging at low and high current rates as curves were symmetric. Presented flexible and electroactive CS/PVA based MnO2 membranes will be highly suitable candidates for bendable electrode material in modern high-tech flexible energy storage devices.

There is a need to develop pro-angiogenic biomaterials to promote wound healing and to assist in regenerative medicine. To this end, various growth factors have been exploited which have the potential to promote angiogenesis. However, these are generally expensive and labile which limits their effectiveness. An alternative approach is to immobilize heparin onto biocompatible degradable hydrogels. The heparin in turn will then bind endogenous proangiogenic growth factors to induce formation of new blood vessels. In this study, we continue our development of hydrogels for wound healing purposes by exploring covalently cross-linking chitosan and polyvinyl alcohol hydrogels using triethyl orthoformate. Two concentrations of triethyl orthoformate (4 and 16%) were compared for their effects on the structure of hydrogels – their swelling, pore size, and rate of degradation and for their ability to support the growth of cells and for their heparin-binding capacity and their effects on angiogenesis in a chick chorioallantoic membrane assay. Hydrogels formed with 4 or 16% both triethyl orthoformate cross-linker were equally cyto-compatible. Hydrogels formed with 4% triethyl orthoformate absorbed slightly more water than those made with 16% triethyl orthoformate and broke down slightly faster than non-cross-linked hydrogels. When soaked in heparin the hydrogel formed with 16% triethyl orthoformate showed more blood vessel formation in the CAM assay than that formed with 4% triethyl orthoformate.

Our aim was to develop a biocompatible hydrogel that could be soaked in heparin and placed on wound beds to improve the vasculature of poorly vascularized wound beds. In the current study, a methodology was developed for the synthesis of a new chitosan derivative (CSD-1). Hydrogels were synthesized by blending CSD-1 for either 4 or 24 h with polyvinyl alcohol (PVA). The physical/chemical interactions and the presence of specific functional groups were confirmed by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance (1H NMR). The porous nature of the hydrogels was confirmed by scanning electron microscopy (SEM). Thermal gravimetric analysis (TGA) showed that these hydrogels have good thermal stability which was slightly increased as the blending time was increased. Hydrogels produced with 24 h of blending supported cell attachment more and could be loaded with heparin to induce new blood vessel formation in a chick chorionic allantoic membrane assay.

Chitosan's 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.

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.

Thymidine phosphorylase (TP) inhibitors have attracted great attention due to their ability to suppress the tumors formation. In our ongoing research, a series of 1,3,4-oxadiazole-2-thione (1-12) has been synthesized under simple reaction conditions in good to excellent yields (86-98%) and their TP inhibition potential has also been evaluated. The majority of synthesized compounds showed moderate thymidine phosphorylase inhibitory activity with IC50 values ranging from 38.24±1.28 to 258.43±0.43μM, and 7-deazaxanthine (7DX) was used as a reference compound (IC50 38.68±4.42). The TP activity was very much dependent on the C-5 substituents; among this series the compound 6 bearing 4-hydroxyphenyl group was found to be the most active with IC50 38.24±1.28μM. Molecular docking studies revealed their binding mode.

A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against α-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC50 value 112.21±0.97 μM), to show the enzyme - inhibitor interactions.

Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer’s disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the tested compounds exhibited inhibitory activity against AChE and BChE. Among them 4f and 6e showed the highest AChE inhibitory activity with IC50 91.21±0.06 and 68.52±0.04 μM, respectively. However compound 5a exhibited the highest inhibitory activity against BChE (IC50 55.21±0.12 μM).