Bioinspired chitosan based functionalization of biomedical implant surfaces for enhanced hemocompatibility, antioxidation and anticoagulation potential: an in silico and in vitro study.

Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including Foeniculum vulgare, Angelica sinensis, and Cinnamomum verum have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.

Evolutionary perspective of drug eluting stents: from thick polymer to polymer free approach.

BACKGROUND: Introduction of Bare Metal Stents (BMS) was itself a revolutionary step in the history of the medical industry; however, Drug Eluting Stents (DES) maintained its superiority over BMS in every aspect from restenosis rate to late lumen loss. The reason behind the magnanimous position of the DES in the stent market is the degree of improvement with which it evolves. New and better stents come into the market every year, surpassing their predecessors by many folds. LITERATURE REVIEW: This review paper discusses the journey of DES with supporting clinical trials in detail. In the first generation, there were stainless-steel stents with thicker coatings. Although they had superior results compared to BMS, there was still room for improvement. Afterward came the second-generation stents, which had superior metal platforms with thinner struts and thin coatings. The drugs were also changed from Paclitaxel and Sirolimus to Zotrolimus and Everolimus. These stents performed best; however, there was an issue of permanent coating, which remained intact over the stent surface after complete drug elution and started to cause issues in longer-term studies. Hence, an improved version of DES was introduced to these permanent coatings called the third generation of drug eluting stents, which initially utilized biodegradable polymer and ultimately moved towards polymer free drug coatings. This generation has introduced a unique amalgam of technologies to achieve its polymer free coatings; however, researchers have numerous prospects of growth in this field. This review paper highlights the major coups of stent technology evolution from BMS to DES, from thick polymeric coatings to thin coatings and from durable polymers to polymer free DES. CONCLUSION: In conclusion, though the medical industry promptly accepted BMS as the best treatment option for cardiovascular diseases; however, DES has provided even better results than BMS. In DES, the first and second generation has ruled the technology for many years and are still on the shelves. Still, the issues aroused due to durable polymer shifted the attention towards biodegradable drug eluting stents, the third generation growing rapidly. But the scientific community has not restricted themselves and is investigating bioresorbable stents that completely eliminate the polymer intervention in drug eluting stent technology.

An Insight into Potential Pharmacotherapeutic Agents for Painful Diabetic Neuropathy.

Diabetes is the 4th most common disease affecting the world's population. It is accompanied by many complications that deteriorate the quality of life. Painful diabetic neuropathy (PDN) is one of the debilitating consequences of diabetes that effects one-third of diabetic patients. Unfortunately, there is no internationally recommended drug that directly hinders the pathological mechanisms that result in painful diabetic neuropathy. Clinical studies have shown that anticonvulsant and antidepressant therapies have proven fruitful in management of pain associated with PDN. Currently, the FDA approved medications for painful diabetic neuropathies include duloxetine, pregabalin, tapentadol extended release, and capsaicin (for foot PDN only). The FDA has also approved the use of spinal cord stimulation system for the treatment of diabetic neuropathy pain. The drugs recommended by other regulatory bodies include gabapentin, amitriptyline, dextromethorphan, tramadol, venlafaxine, sodium valproate, and 5 % lidocaine patch. These drugs are only partially effective and have adverse effects associated with their use. Treating painful symptoms in diabetic patient can be frustrating not only for the patients but also for health care workers, so additional clinical trials for novel and conventional treatments are required to devise more effective treatment for PDN with minimal side effects. This review gives an insight on the pathways involved in the pathogenesis of PDN and the potential pharmacotherapeutic agents. This will be followed by an overview on the FDA-approved drugs for PDN and commercially available topical analgesic and their effects on painful diabetic neuropathies.

Synthesis and Appraisal of Natural Drug-Polymer-Based Matrices Relevant to the Application of Drug-Eluting Coronary Stent Coatings.

Cardiovascular diseases are becoming a leading cause of death in the world, and attention is being paid to develop natural drug-based treatment to cure heart diseases. Curcumin, ginger, and magnolol are pharmaceutically active in many ways, having properties including anticoagulation, antiproliferation, anti-inflammatory, and antioxidant, and may be used to synthesis coatings for drug-eluting stents to treat cardiovascular diseases. In the present investigation, a degradable polymer with varying molecular weights was used as a drug carrier to control the degradation of polymer; three different natural drugs such as curcumin, magnolol, and ginger were used owing to their reported pharmacological properties. The results of in vitro measurements of all three natural drugs released from drug-loaded polymeric films showed an initial burst release followed by a sustained release for up to 38 days of measurement. On the other hand, different levels of hemocompatibility were observed by varying concentrations of natural drugs in human erythrocytes. As per the ASTM F756 standard, ginger having low concentration showed optimum hemocompatibility with regard to the drug-eluting stent application as compared with magnolol and curcumin concentrations, which showed suboptimal hemocompatibility and fall in the range of mild-to-severe blood toxicity category. The structure of the coating films was characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) with results suggesting that there was no chemical bonding between the polymer and drug. Thus, according to this study, it can be concluded that after more detailed in vitro testing such as hemocompatibility tests and platelet adhesion testing, ginger can be a better candidate as a drug-coating material for drug-eluting stent applications.

Synthetic polymeric biomaterials for wound healing: a review.

Wounds are of a variety of types and each category has its own distinctive healing requirements. This realization has spurred the development of a myriad of wound dressings, each with specific characteristics. It is unrealistic to expect a singular dressing to embrace all characteristics that would fulfill generic needs for wound healing. However, each dressing may approach the ideal requirements by deviating from the 'one size fits all approach', if it conforms strictly to the specifications of the wound and the patient. Indeed, a functional wound dressing should achieve healing of the wound with minimal time and cost expenditures. This article offers an insight into several different types of polymeric materials clinically used in wound dressings and the events taking place at cellular level, which aid the process of healing, while the biomaterial dressing interacts with the body tissue. Hence, the significance of using synthetic polymer films, foam dressings, hydrocolloids, alginate dressings, and hydrogels has been reviewed, and the properties of these materials that conform to wound-healing requirements have been explored. A special section on bioactive dressings and bioengineered skin substitutes that play an active part in healing process has been re-examined in this work.

Electromechanically Actuated Multifunctional Wireless Auxetic Device for Wound Management.

The design and fabrication of a wound healing device for chronic wounds, with multiple functions for controlled drug delivery and exudate removal, has been described in this paper. The structural features have been machined and modified through laser cutting in a biocompatible polymer cast. Miniaturized versions of electronically actuated (lead-screw and pulley) mechanisms are used for the specific purpose of controlled drug delivery. These mechanisms have been studied and tested, being controlled through a microcontroller setup. An auxetic polymeric barrier membrane has been used for restricting the drug quantities administered. Drug delivery mechanisms are powered wirelessly, through an external, active RF component; this communicates with a passive component that is buried inside the wound healing device. The exudate removal efficiency of the device has been assessed through several simple tests using simulated wound exudate. It has been found that reasonably precise quantities of drug dosages to be administered to the wound site can be controlled through both drug delivery mechanisms; however, the lead-screw mechanism provides a better control of auxetic barrier membrane actuation and hence controlled drug delivery. We propose that this device can have potential clinical significance in controlled drug delivery and exudate removal in the management of chronic wounds.

New Biofunctional Loading of Natural Antimicrobial Agent in Biodegradable Polymeric Films for Biomedical Applications.

The study focuses on the development of novel Aloe vera based polymeric composite films and antimicrobial suture coatings. Polyvinyl alcohol (PVA), a synthetic biocompatible and biodegradable polymer, was combined with Aloe vera, a natural herb used for soothing burning effects and cosmetic purposes. The properties of these two materials were combined together to get additional benefits such as wound healing and prevention of surgical site infections. PVA and Aloe vera were mixed in a fixed quantity to produce polymer based films. The films were screened for antibacterial and antifungal activity against bacterial (E. coli, P. aeruginosa) and fungal strains (Aspergillus flavus and Aspergillus tubingensis) screened. Aloe vera based PVA films showed antimicrobial activity against all the strains; the lowest Aloe vera concentration (5%) showed the highest activity against all the strains. In vitro degradation and release profile of these films was also evaluated. The coating for sutures was prepared, in vitro antibacterial tests of these coated sutures were carried out, and later on in vivo studies of these coated sutures were also performed. The results showed that sutures coated with Aloe vera/PVA coating solution have antibacterial effects and thus have the potential to be used in the prevention of surgical site infections and Aloe vera/PVA based films have the potential to be used for wound healing purposes.

Auxetic polymeric bone plate as internal fixator for long bone fractures: Design, fabrication and structural analysis.

INTRODUCTION: Injuries cover about 11% of World's Disease Burden depicting fractures to be the leading severe consequence of trauma. Fractures occur due to force impact or osteoporosis. Fracture healing is a complicated process. Fracture fixation techniques focus on imparting reduction to fractured fragments and induce healing. When considering possible fixation methods, the aspect of micro-movement is an important one, as this induces callus formation which tends to be a crucial step for fracture healing. Internal fixation of long bone fractures using metallic plates has been carried out since decades and recently advancements have been in synthesizing biodegradable plates as well. The purpose of this research was to fabricate an Auxetic Polymeric Bone Plate that can be used as an internal fixator for long bone fracture; this bone plate renders micro-movement due to its counter intuitive behavior, has the potential to reduce the effect of stress shielding and allow the same range of motion as that of natural bone. METHODS: Polyurethane was chosen as a material for the fabrication of the Auxetic device because of its biocompatibility and non-toxic effects. The plate was then tested for mechanical properties such as Tensile and Compression testing to determine the strength. RESULTS AND DISCUSSION: The tensile testing of the Auxetic polyurethane specimens showed that the mean of the Poisson's ratio of the samples lies between -0.68 and -0.87 at different uni-axial tensile load values. The Auxetic structure of our device has the potential to allow for efficient fixation because its negative Poisson's ratio offers micro-movement, thereby causing fixation with relative stability rather than absolute stability. The Auxetic bone plate can be superior to contemporary plate fixation systems, as it demands meaningfully small contact points. The suitable mechanical properties might lessen stress shielding effects that are normally caused by rigid bone plates. The Auxetic nature of the bone will help align and sustain the bone fragments with small fracture gaps in order to impart appropriate assembly to accomplish bone healing.

Auxetic coronary stent endoprosthesis: fabrication and structural analysis.

BACKGROUND: Cardiovascular heart disease is one of the leading health issues in the present era and requires considerable health care resources to prevent it. The present study was focused on the development of a new coronary stent based on novel auxetic geometry which enables the stent to exhibit a negative Poisson's ratio. Commercially available coronary stents have isotropic properties, whereas the vascular system of the body shows anisotropic characteristics. This results in a mismatch between anisotropic-isotropic properties of the stent and arterial wall, and this in turn is not favorable for mechanical adhesion of the commercially available coronary stents with the arterial wall. It is believed that an auxetic coronary stent with inherent anisotropic mechanical properties and negative Poisson's ratio will have good mechanical adhesion with the arterial wall. METHODS: The auxetic design was obtained via laser cutting, and surface treatment was performed with acid pickling and electropolishing, followed by an annealing process. In vitro mechanical analysis was performed to analyze the mechanical performance of the auxetic coronary stent. Scanning electronic microscopy (SEM) was used to determine the effects of fabrication processes on the topography of the auxetic stent. RESULTS AND CONCLUSIONS: The elastic recoil (3.3%) of the in vitro mechanical analysis showed that the auxetic stent design effectively maintained the luminal patency of the coronary artery. Also, the auxetic coronary stent showed no foreshortening, therefore it avoids the problem of stent migration, by expanding in both the radial and longitudinal directions. By virtue of its synclastic behavior, the auxetic stent bulges outward when it is radially expanded through an inflated balloon.

Auxetic oesophageal stents: structure and mechanical properties.

Oesophageal cancer is the ninth leading cause of malignant cancer death and its prognosis remains poor, ranking as the sixth most frequent cause of death in the world. This research work aims to adopt an Auxetic (rotating-squares) geometry device, that had previously been examined theoretically and analysed by Grima and Evans (J Mater Sci Lett 19(17):1563-1565, 2000), to produce a novel Auxetic oesophageal stent and stent-grafts relevant to the palliative treatment of oesophageal cancer and also for the prevention of dysphagia. This paper discusses the manufacture of a small diameter Auxetic oesophageal stent and stent-graft. The oral deployment of such an Auxetic stent would be simplest if a commercial balloon dilatational catheter was used as this obviates the need for an expensive dedicated delivery system. A novel manufacturing route was employed in this research to develop both Auxetic films and Auxetic oesophageal stents, which ranged from conventional subtractive techniques to a new additive manufacturing method. Polyurethane was selected as a material for the fabrication of Auxetic films and Auxetic oesophageal stents because of its good biocompatibility and non-toxicological properties. The Auxetic films were later used for the fabrication of seamed Auxetic oesophageal stents. The flexible polyurethane tubular grafts were also attached to the inner luminal side of the seamless Auxetic oesophageal stents, in order to prevent tumour in-growth. Scanning electron microscopy was used to conduct surface morphology study by using different Auxetic specimens developed from different conventional and new additive manufacturing techniques. Tensile testing of the Auxetic films was performed to characterise their mechanical properties. The stent expansion tests of the Auxetic stents were done to analyse the longitudinal extension and radial expansion of the Auxetic stent at a range of radial pressures applied by the balloon catheter, and to also identify the pressure values where the Auxetic stent fails. Finite element models of both Auxetic film and Auxetic stent were developed, and the results were compared with experimental results with a good agreement. The tensile testing of the Auxetic polyurethane films revealed that the Poisson's ratio of the sample ranged between -0.87 and -0.963 at different uniaxial tensile load values. From the stent expansion test, it was found that the Auxetic oesophageal stent radially expanded from 0.5 to 5.73 mm and longitudinally extended from 0.15 to 1.83 mm at a range of applied pressure increments (0.5-2.7 bar) from the balloon catheter.