Search

Schwann cell-derived matrix coated scaffolds for peripheral nerve regeneration.

Purpose: Nanomaterials have a plethora of applications in the field of dental sciences. Due to their peculiar properties and distinguishing characteristics, nanomaterials are used as candidates for coating titanium, acrylic, and PLA/PCL-based dental implants. This article reviews various nanomaterials that can impart antibacterial properties and be used as implant coating materials. Methods: Research articles published between 1992 and 2021, based on nanomaterial coatings for dental applications, were retrieved from Google Scholar and were thoroughly studied. Results: The research articles reviewed indicated that a substantial amount of progress had been made in the area of antibacterial resistance of nanomaterial-based coatings for dental implants. This work’s main contribution lies in a comprehensive review of the various nanostructures that inhibit the nurturing of bacterial biofilms on implants, thus diminishing the probability of any infection. Significance: Given the reported results, additional clinical research and investigation on nanostructure-coated implants aids in efficient implementation.

Curcumin, a potent phytochemical derived from the spice element turmeric, has been identified as a herbal remedy decades ago and has displayed promise in the field of medicinal chemistry. However, multiple traits associated with curcumin, such as poor bioavailability and instability, limit its effectiveness to be accepted as a lead drug-like entity. Different reactive sites in its chemical structure have been identified to incorporate modifications as attempts to improving its efficacy. The diketo group present in the center of the structural scaffold has been touted as the group responsible for the instability of curcumin, and substituting it with a heterocyclic ring contributes to improved stability. In this study, four heterocyclic curcumin analogues, representing some broad groups of heterocyclic curcuminoids (isoxazole-, pyrazole-, N-phenyl pyrazole- and N-amido-pyrazole-based), have been synthesized by a simple one-pot synthesis and have been characterized by FTIR, 1H-NMR, 13C-NMR, DSC and LC–MS. To predict its potential anticancer efficacy, the compounds have been analyzed by computational studies via molecular docking for their regulatory role against three key proteins, namely GSK-3β—of which abnormal regulation and expression is associated with cancer; Bcl-2—an apoptosis regulator; and PR which is a key nuclear receptor involved in breast cancer development. One of the compounds, isoxazole-curcumin, has consistently indicated a better docking score than the other tested compounds as well as curcumin. Apart from docking, the compounds have also been profiled for their ADME properties as well as free energy binding calculations. Further, the in vitro cytotoxic evaluation of the analogues was carried out by SRB assay in breast cancer cell line (MCF7), out of which isoxazole-curcumin (IC50–3.97 µM) has displayed a sevenfold superior activity than curcumin (IC50–21.89 µM). In the collation of results, it can be suggested that isoxazole-curcumin behaves as a potential lead owing to its ability to be involved in a regulatory role with multiple significant cancer proteins and hence deserves further investigations in the development of small molecule-based anti-breast cancer agents. Graphic abstract

The aim of this study was to investigate the effect of altering design variables like cross-linking and freezing temperature (at a time) on morphology of freeze-dried chitosan scaffolds and modulation of release of Diclofenac sodium (model drug). Freeze-dried chitosan scaffolds produced at − 80 °C, cross-linked with genipin, showed swelling of 163.52 ± 9.95% with sustained drug release of 26.37 ± 10.47% over 24 h (P

The human Abl kinases comprise a family of proteins that are known to be key stimulus drivers in the signaling pathways modulating cell growth, cell survival, cell adhesion, and apoptosis. Recent collative studies have indicated the role of activation of Abl and Abl-related genes in solid tumors; further terming the Abl kinases as molecular switches which promote proliferation, tumorigenesis, and metastasis. The up-regulated Abl-kinase expression in colorectal cancer (CRC) and the role of Abl tyrosine kinase activity in the Matrigel invasion of CRC cells have cemented its significance in CRC advancement. Therefore, the requisite of identifying small molecules which serve as Abl selective inhibitors and designing anti-Abl therapies, particularly for CRC tumors, has driven this study. Curcumin has been touted as an effective inhibitor of cancer cells; however, it is limited by its physicochemical inadequacies. Hence, we have studied the behavior of heterocyclic derivatives of curcumin via computational tools such as pharmacophore-based virtual screening, molecular docking, free-energy binding, and ADME profiling. The most actively docked molecule, 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-carboxamide, was comparatively evaluated against Curcumin via molecular dynamics simulation using Desmond, Schrödinger. The study exhibited the improved stability of the derivative as compared to Curcumin in the tested protein pocket and displayed the interaction bonds with the contacted key amino acids. To further establish the claim, the derivatives were synthesized via the mechanism of cyclization of Curcumin and screened in vitro using SRB assay against human CRC cell line, HCT 116. The active derivative indicated an IC50 value of 5.85 µM, which was sevenfold lower as compared to Curcumin’s IC50 of 35.40 µM. Hence, the results base the potential role of the curcumin derivative in modulating Abl-kinase activity and in turn may have potential therapeutic value as a lead for CRC therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-021-03051-9.

Microneedle delivery patches are an emerging technology to attain painless and sustained delivery through the epidermis of the skin. This study is unique in its attempt to develop polymeric microneedles embedded with drug. Special polymer chitosan with hydrogel forming capability is cross-linked with PVA, a water-soluble polymer with excellent film strengthening ability and loaded with model drug diclofenac sodium. The microneedle patch was fabricated by pouring the chitosan-PVA solution (ratio 1:6) on negative replica of master mold, which upon drying was peeled off to result in the composite film. The film of chitosan-PVA in the ratio 1:6 when tested for mechanical behavior exhibited improved mechanical strength owing to use of PVA, the presence of effective cross-linking of PVA with chitosan was further verified with FTIR. The release from drug-loaded needles was promising, as cross-linking with PVA enabled a sustained drug release of 20.17% at the end of 30 h. The release followed the Higuchi model with Fickian diffusion, indicating a swelling-dependent release. The microneedle prepared using a composite of chitosan-PVA showed promising results indicating its potential to be used as a drug eluting transdermal patch.

Curcumin is a pharmacologically active polyphenol derived from the popular spice element-Turmeric. The therapeutic activity of curcumin has been extensively investigated over the last few decades and reports suggest the role of curcumin in a large number of biological activities, particularly its prominent anticancer activity. Curcumin, being a pleiotropic molecule, is a regulator of multiple molecular targets which play crucial roles in various cell signaling pathways. It is known to suppress transformation, inhibit proliferation as well as induce apoptosis. However, despite all these benefits, the efficacy of curcumin remains limited due to its poor bioavailability, poor absorption within the systemic circulation and rapid elimination from the body. To overcome these limiting factors, researchers all around the world are working towards designing a synthetic and superior curcuminoid by making suitable structural modifications to the parent skeleton. These curcuminoids, mainly analogues and derivatives, will not only improve the physicochemical properties but also enhance the efficacy simultaneously. The present review will provide a comprehensive account of the analogues and derivatives of curcumin that have been reported since 2014 which have indicated a better anticancer activity than curcumin.

Wound healing restores the integrity of damaged tissues by a multistep process which involves coagulation, inflammation, and matrix synthesis. The dressing of the wound is critical in the wound healing treatment because it works as a protective barrier sandwiched between the site of injury and the environment outside the vicinity of the wound. With the advancements in tissue engineering and regenerative medicine, wound management has transformed from being simple coverings to advanced technological matrices which not only prevents infections but also enhances the recovery process of the dermal and epidermal tissues. Studies have indicated that fibroblasts produce several extracellular matrix molecules, glycosaminoglycan (GAG) being one of them. GAG is responsible for cell–cell and cell–matrix interactions and regulates signaling factors associated with wound healing. Recent studies indicate that natural polysaccharides assist the functionalization of GAG activity furthering the process of wound healing. This chapter aims at studying the role of natural polysaccharides in detail and enlists the different types of polysaccharides adopted for the wound healing process.

Cancer, the abnormal proliferation of cells, is one of the leading causes of death in the world. A number of challenges hamper its treatment regime, such as ineffective drug concentration reaching the target site, nonspecific distribution of drug and acquired resistance upon chemotherapy due to various drugs and dosage. With a deeper understanding of tumor biology and the advancement in pharmaceutical technology, drug delivery vehicles have been recognized as a suitable approach in its treatment. This anticancer therapy aims to improve the pharmacokinetics of the drug, accumulate the drug at the target site and reduce the toxic effects on healthy tissues. This chapter provides an insight into the approach to the treatment of cancer, the advances in 3D tumor model studies, the various drug delivery strategies adopted and the challenges identified while working with these drug delivery systems.

In this study, multiple control systems were developed using commonly used wireless communication protocols like Bluetooth, Xbee, and Wi-Fi. Mechanical switch based control systems were initially designed using Xbee and Bluetooth protocols. Further, Android application based control systems were developed using Bluetooth and Wi-Fi protocols. A robotic vehicle was used as an electric-powered wheelchair prototype. Ultrasonic sensors and infrared sensors were integrated with the robotic vehicle for obstacle and pothole detection, respectively. The control systems were tested in an L-shaped corridor for identifying the suitable wireless communication protocol to efficiently guide the robotic vehicle through a scheduled navigational pathway. Both Xbee and Wi-Fi technology based control systems were able to guide the robotic vehicle through the corridor. But the implementation of Xbee communication protocol is economic. However, for shorter distances, Bluetooth technology may be used for cost-effective implementation.

The current study discusses about the development of an EMG based wireless control system for the patients suffering from high-level motor disability. Surface EMG (sEMG) signals were processed in the time domain and using discrete wavelet transforms (DWT). The statistical features of the signals (sEMG, envelope of the squared sEMG and wavelet processed sEMG) were determined and analyzed. The analysis of the features suggested that the features of the envelope of the squared sEMG signals were sufficient to be used for high-efficiency classification and control signal generation. A hall-effect sensor based switching mechanism was introduced for controlling the duration of the activation of the device. The control signals were wirelessly transmitted to the assistive device (robotic vehicle). The training and the subsequent use of the developed control system were easy.

A scaffold serves as structural support for cell attachment which further leads to the development of tissues. The design of a scaffold is an important prototype to allow the attachment of the cells, to retain the integrity of the cells, as well as to have the required mechanical strength to have a beneficial impact on the organ. Recent trends in research suggest that biopolymer-based scaffolds have indicated great biocompatibility and are excellent mimics of the extracellular matrix systems. This chapter elucidates the various properties and types of scaffolds, methods of fabrication of such scaffolds, the most suitable biopolymers that have been used to design the scaffolds, and their recent applications in tissue engineering and drug delivery.

Tamarind gum (TG) polysaccharide has shown great potential in food and pharmaceutical applications due to their viscosity-modulating properties. In this study, TG hydrogels of varied concentrations were developed by physical gelation method. The prepared hydrogels were characterized by microscopy, XRD, FTIR, mechanical, electrical and drug release studies. Microscopic studies showed formation of globular structures throughout the matrix. XRD and FTIR studies suggested an increase in the associative interactions when the TG content was increased, which in turn resulted in the alteration in the mechanical properties. An increase in the intrinsic ionic conductivity was predicted from the electrical studies. This increase in intrinsic ionic conductivity modulated the release of the drug from the hydrogels. The drug was released in its active form. In gist, it can be concluded that the physical hydrogels prepared using TG may be explored as matrices for drug delivery applications.

A recent trend in microfabrication technology involves the development of advanced forms of drug delivery devices. These microfabricated devices can be designed to specific dimensions providing site specific and controlled delivery of therapeutics in addition to ease of penetration across barriers. This chapter provides an overview of the microfabrication technology and its applications in drug delivery. It emphasizes the use of microfabrication technology in developing microneedles and provides detailed microneedle characterization techniques for their application in transdermal drug delivery.

Curcumin, a potent phytochemical, has been a significant lead compound and has been extensively investigated for its multiple bioactivities. Owing to its natural origin, non-toxic, safe, and pleiotropic behavior, it has been extensively explored. However, several limitations such as its poor stability, bioavailability, and fast metabolism prove to be a constraint to achieve its full therapeutic potential. Many approaches have been adopted to improve its profile, amongst which, structural modifications have indicated promising results. Its symmetric structure and simple chemistry have prompted organic and medicinal chemists to manipulate its arrangement and study its implications on the corresponding activity. One such recurring and favorable modification is at the diketo moiety with the aim to achieve isoxazole and pyrazole analogues of curcumin. A modification at this site is not only simple to achieve, but also has indicated a superior activity consistently. This review is a comprehensive and wide-ranged report of the different methods adopted to achieve several cyclized curcumin analogues along with the improvement in the efficacy of the corresponding activities observed.

Constant escalations in the number of diabetics’ worldwide, associated complications and financial implications, failure of conventional therapy regimen to restore normoglycemia has brought to limelight the non-pharmacologic means like lifestyle and dietary interventions as one of the effective aids to combat type 2 diabetes. Economy, education, preference plays a role in dietary selection. Prolonged intake of carbohydrate enriched diet was found to be a causative of diabetes amongst poor rural Indian population of Bengal. Contrastingly, current research of three years RCT amongst rural Bengalis have shown that a daily increase in protein intake by 25-30% when compared with standard rural diet comprising of about 70% to 80% of carbohydrate, 10% fats and 10% protein, improved insulin sensitivity and lowered fasting blood glucose level amongst experimental population significantly (p=0.04) rather than the control group. Fasting serum insulin value decreased from 47±2.2 pmol/l to 44±2.4 pmol/l (p=0.04) in the study group but amongst controls an increment from 42±2.4 pmol/l to 43±2.4 pmol/l was observed. Fasting Blood Sugar level amongst controls was initially 103±4 mg/dl and became 105±6 mg/dl but in the experimental group initial value of 109±12 mg/dl diminished to 103±8 mg/dl (p=0.04) at the end of 3 years follow up. However blood lipid parameters (TC, LDL, HDL, and VLDL) were not significantly influenced by higher daily protein intake both in control and experimental group. Thus a conclusive fact found from the trial is that protein enriched, low carbohydrate diet can offer a positive impact on glycemic control kidney functions remaining normal. (250 words)

Chitosan (CS) is a naturalcationic polysaccharide obtained by deacetylation of chitin, a biopolymer found mainly in the exoskeleton of crab, shrimp shells, etc. The chitosan degree of deacetylation (DD) is an important factor which determines some of the physiochemical and biological properties of chitosan. The present study focuses on evaluating the effect of chitosan DD on nanoparticle size by using three different DD of chitosan, i.e., 85%, 90% and 93%. Chitosan nanoparticles were prepared by ionic gelation method using sodium tripolyphosphate (TPP) as crosslinker. The particle size and polydispersity index (PDI) was studied using Dynamic Light Scattering (DLS) and was further characterized by Fourier Transform Infrared spectroscopy (FTIR) to confirm the interactions between the ammonium groups of CS and tripolyphosphoric groups of TPP in the prepared nanoparticles. The results demonstrated that nanoparticles prepared using 85% DD chitosan had an average particle size of 100.2 ± 0.5 nm.

A popular approach to attaining controlled drug delivery from polymer based systems involves the use of cross-linkers. In order to improve the properties of polymers specific to their applications, they can be modified by either physical cross-linkers (high pressure, irradiation) or chemical cross-linkers (glutaraldehyde, genipin). This chapter provides an insight into the different types and mechanisms of cross-linking. It reviews the existing drug delivery systems to understand the effects of cross-linking in them. The recent applications of cross-linked polymeric drug delivery and tissue engineering systems are also discussed.

Protein-based gels contain proteins and peptides as the structural elements. By virtue of their bioactive nature and high water retention capacity, these hydrogels act as important carrier matrices for biomedical applications. This chapter gives an insight into the unique properties of the major proteins (e.g., collagen, elastin, gelatin, silk protein), which are used as the structuring material for the fabrication of the protein-based gels. It provides a comprehensive review of the methods of preparation and the applications of the protein-based gels in drug delivery and tissue engineering.

A popular approach to attaining controlled drug delivery from polymer based systems involves the use of cross-linkers. In order to improve the properties of polymers specific to their applications, they can be modified by either physical cross-linkers (high pressure, irradiation) or chemical cross-linkers (glutaraldehyde, genipin). This chapter provides an insight into the different types and mechanisms of cross-linking. It reviews the existing drug delivery systems to understand the effects of cross-linking in them. The recent applications of cross-linked polymeric drug delivery and tissue engineering systems are also discussed.

The current study delineates the effect of Odia and Tamil music on the Autonomic Nervous System (ANS) and cardiac conduction pathway of Odia volunteers. The analysis of the ECG signals using Analysis of Variance (ANOVA) showed that the features obtained from the HRV domain, time-domain and wavelet transform domain were statistically insignificant. But non-linear classifiers like Classification and Regression Tree (CART), Boosted Tree (BT) and Random Forest (RF) indicated the presence of important features. A classification efficiency of more than 85% was achieved when the important features, obtained from the non-linear classifiers, were used. The results suggested that there is an increase in the parasympathetic activity when music is heard in the mother tongue. If a person is made to listen to music in the language with which he is not conversant, an increase in the sympathetic activity is observed. It is also expected that there might be a difference in the cardiac conduction pathway.

Chitosan hydrogels are widely studied as drug delivery vehicles. The present work involves investigating the effects of cross-linking on morphology of chitosan gels and their impact on the curcumin release from cross-linked gel matrices. Chitosan usually suffers from poor mechanical strength so to improve the mechanical and thermal stability the gels are often chemically cross-linked. In this study, chitosan hydrogels are prepared and then the gels are cross-linked with glutaraldehyde (synthetic cross-linker) and genipin (a naturally occurring cross-linker). Cross-linked gels are subjected to a number of tests, such as compression test, swelling study, and scanning electron microscopy analysis. Release study was performed by forming drug loaded gels by incorporating curcumin into the chitosan matrices. Morphological analysis for the cross-linked gels revealed compact network structure. Chitosan gel cross-linked with genipin, indicated higher compressive strength (0.1539 + 0.03) MPa than gel cross-linked with glutaraldehyde (0.032 + 0.01) MPa. Gels cross-linked with glutaraldehyde showed higher swelling and also higher release of curcumin ∼90.67% whereas, genipin cross-linked gels having more compact network shows better release profile of curcumin ∼79.26% over 24 hours (P

Hydrogels have evolved over the last decade as materials of choice in varied biomedical applications. This is associated with the inherent biocompatible nature of the hydrogels. The modulation of the properties of the hydrogels is easily possible due to the availability of polymers of varied chemistry and physical properties. This review discusses the pharmaceutical aspects of the controlled release of bioactive agents from hydrogel-based formulations.

Though chitosan hydrogels have shown potential for numerous tissue regeneration applications, its insolubility above pH 6.0 have greatly limited applicability in encapsulation of live cells and pH sensitive bioactive agents. In this report an approach to overcome this limitation was tested with phosphorylated derivative of chitosan, N-methylene phosphonic chitosan (NMPC). NMPC is also known to possess efficacious gene delivery, biomineralization, and osteoinduction properties. NMPC hydrogels were synthesized by cross-linking NMPC with either glutaraldehyde (NMPC-GLU) or genipin (NMPC-GEN). An increase in pH from 3.0 to 6.8 reduced gelation time with both the agents, with the reduction more pronounced in NMPC-GLU. The results correlated with the reaction mechanisms of both agents with NMPC. Further NMPC-GEN gels demonstrated higher elastic modulus and compressive strength values. Cell culture studies showed higher cell proliferation on NMPC-GEN compared to NMPC-GLU. [Supplementary materials are available f...

In recent years, chitosan, a biocompatible natural polymer, having a cellulosic backbone has gained importance in various biomedical applications like wound healing, tissue engineering, surface modifications of implantable devices, and drug delivery. This may be attributed to the versatile chemistry of the polymer. Various chitosan-mediated delivery systems have been developed to improve the bioavailability of drug(s) and be categorized either as nanoparticulate, microparticulate, or macro delivery systems. All these delivery systems have their own advantages and limitation as a delivery vehicle. This review gives an overview of the chitosan-based drug delivery systems.

A composite hydrogel, using chitosan and gelatin was formulated. Chitosan-gelatin hydrogel in ratio 0.5:1 was prepared in lactic acid (2%). The poor mechanical strength of the gel was overcome by crosslinking with 1% (w/v) genipin solution. The properties of composite hydrogel were tested based on the characterizations performed. Swelling test was performed by immersing cross-linked hydrogels in water for 20 hours and swelling indices were calculated. Infrared (IR) spectroscopy was done to ensure presence of crosslinking. In-vitro release of uncross-linked and crosslinked hydrogels were performed and subsequently, release kinetics of two drugs: curcumin (weak base) and diclofenac sodium (weak acid) were studied. Cumulative release was carried out in deionized water for 30 hours for both the drugs and was analyzed spectrophotometrically at 265nm for curcumin and 276nm for diclofenac sodium. Cross-linked hydrogel showed swelling of 99.28±0.04% for 20 hours. Release profile of curcumin loaded cross-linked hydrogel showed sustained release of about 80.04±0.54% over 30 hours; found best fit with Higuchi model following anomalous transport (n=0.90), while diclofenac sodium loaded cross-linked gel exhibited sustained release of about 71.72±0.04 % over 30 hours; found best fit with Higuchi model following Fickian diffusion (n=0.45). Overall, the results indicated that the cross-linked composite hydrogel could be tuned as a carrier for the transport of both acidic and basic biomolecules.

Surface EMG (sEMG) signals from the palmaris longus, flexor carpi radialis and flexor carpi ulnaris muscles were recorded using an in-house developed EMG signal acquisition system. The bandwidth of the acquisition system was 1500 Hz. The extracted sEMG signal was processed using Discrete Wavelet Transform (DWT). The features of the extracted and the wavelet processed signals were determined and were used for probable classification using Artificial Neural Network (ANN). A classification efficiency of more than 90% was achieved using ANN classifiers. The results suggested that the sEMG may be successfully used for designing efficient control system.

In this study, the effect of slow and fast music on the heart rate variability and conduction pathway of the heart was studied. The results indicated an increase in the parasympathetic dominance as the volunteers were made to listen to music. The magnitude of the parasympathetic activity was higher when the volunteers were made to listen to fast music. This indicates that slow and fast music affected the sympatho-vagal balance in different proportions. The analysis of the ECG signal and wavelet transformed ECG signal suggested an alteration in the conduction pathway of the heart.

By virtue of their capacity to retain signifi cant amounts of fl uid within their polymeric networks, hydrogels have been used for innumerable biomedical applications. This entry highlights hydrogel-based drug delivery and tissue engineering applications based on naturally occurring biopolymers. It provides a comprehensive review of the biopolymers commonly used in such applications, how hydrogels are typically prepared and characterized, the importance of crosslinking in modulating gel release properties and rheology, examples of recent applications, and possible future applications for novel hydrogels

An effort has been made to prepare gel matrices using different concentrations of Carrageenan whose particle sizes could be exploited in the nanoscale. The Single emulsion technique has been employed for gel formulation. After formulation, gels were characterized for their particle size and zeta potential. Fourier Transform Infrared Spectroscopy (FTIR) was used in the analysis of nanogels, scanning electron microscopy (SEM) to envision the surface microstructures was also performed. It was found that average particle size was in the range of 2000- 4000 nm after drug entrapment and the particles were found to be spherical in shape. The entrapment efficiency of the model drug (Indomethacin) in gel matrix was found to be nearly 40%. Finally, the in vitro release profiles of indomethacin from the nanogel matrices were evaluated spectrophotometrically at 266 nm. Drug release from nanogel consisting of 4% carrageenan was found to be 68% for up to 24 h. Finally, the results have indicated that the Carrageenan nanogel carriers could be used for drug delivery applications.

Drug delivery is a promising technique to enhance the therapeutic efficacy of the drug. However, properties of carrier materials require intense improvement for effective transport of drug molecules. In the current study, attempts have been made to develop freeze dried gelatin matrices cross linked with genipin at various temperatures (5°C, 15°C and 25°C) prior to freeze-drying (-80°C). The freeze dried matrices thus obtained at the said temperatures are characterized for crosslinking density, compression strength, swelling behaviors. The matrix crosslinked at 25°C showed highest Flory-Rehner crosslinking density (467 ± 46) (p