ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy. RESULTS: The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s. CONCLUSION: In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.

Piezoelectric-based bioactive zinc oxide-cellulose acetate electrospun mats for efficient wound healing: an in vitro insight.

Being a complex physiological process involving the removal of damaged tissue debris and creating a new microenvironment for host tissue regeneration, wound healing is still a major challenge for healthcare professionals. Disruption of this process can lead to tissue inflammation, pathogenic infections, and scar formation. Current wound healing treatments primarily focus on passive tissue healing, lacking active engagement in the healing process. In recent years, a new class of functional biomaterials based on piezoelectric properties has emerged, which can actively participate in the wound healing process by harnessing mechanical forces generated from body movement. Herein, we have fabricated a bioactive Cellulose Acetate (CA) electrospun nanofibrous mat incorporating zinc oxide (ZnO) and investigated its efficiency for accelerated wound healing. We have characterized the physicochemical properties of the fabricated nanofibrous mats using various assays, including SEM, FTIR, TGA, mechanical testing, degradation analysis, porosity measurement, hemolysis assay, and piezoelectric d33 coefficient measurement. Through our investigation, we discovered the tunned piezoelectric coefficient of fabricated specimens due to incorporating ZnO into the CA fibers. In vitro studies also confirmed enhanced cell adhesion, proliferation, and migration, indicating faster wound healing potential. Overall, our findings support the efficacy of piezoelectric-based ZnO-incorporated bioactive CA nanofibrous mats for efficient wound healing.

Cellulose-based bioabsorbable and antibiotic coated surgical staple with bioinspired design for efficient wound closure.

The quest to design a flawless wound closure system began long ago and is still underway. Introducing surgical staples is one of the most significant breakthroughs in this effort. In this work, we developed a biodegradable surgical staple to meet the optimal wound closure system criteria and other clinical requirements, such as radiography compatibility and secondary infection prevention. To meet these requirements, a naturally derived cellulose acetate (CA) fiber-reinforced poly-(l-lactic acid) (PLLA) composite was synthesized, and its physicochemical properties were determined using several characterizations such as Fourier-transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and Universal testing machine (UTM), etc. Taking cues from the Mantis's foreleg, a novel staple design was implemented and verified using Finite Element Analysis (FEA). The CA + PLLA staples were fabricated using melt-casted/3D-printing processes. The staples exhibited excellent biodegradation in both wound and physiological microenvironments with sufficient puncturing strength and later closed the wound's edges mechanically. In addition, the CA + PLLA staples also exhibit metal-like ductility properties to withstand horizontal skin tensions during the healing process. Further, the staples are coated with an antibiotic to combat infections effectively to provide better healing.

Current challenges in identification of clinical characteristics and detection of COVID-19: A comprehensive review.

World Health Organization (WHO) declares the COVID-19 outbreak as a pandemic. The newly emerging infection has caused around one million deaths worldwide and still counting. There is no specific treatment for the disease, and it can only contain by breaking the spread. So that early and rapid diagnosis of the infection is the only way to control the outbreak. The COVID-19 virus affects the human respiratory system and subsequently infects other vital organs. In consideration of the diagnosis, the present review focuses on the critical diagnostic approaches for COVID-19, including RT-PCR, Chest-CT scan, some biosensor-based systems, etc. Moreover, this review is a specific bird's eye view on recent developments on the point of care devices and related technologies. Additionally, it presented a small glimpse of the pathophysiology and structural aspects of COVID-19. Therefore, the current review can motivate and help the reader to develop cutting-edge diagnostic technologies for the early and rapid detection of the COVID-19.

Graphene Oxide Reinforcement Enhances the Piezoelectric and Mechanical Properties of Poly(3-hydroxybutyrate-co-3-hydroxy valerate)-Based Nanofibrous Scaffolds for Improved Proliferation of Chondrocytes and ECM Production.

The discovery of piezoelectricity in natural cartilage has inspired the development of piezoelectric biomaterials for its repair and regeneration using tissue engineering approaches. In the present work, piezoelectric scaffolds composed of poly(3-hydroxybutyrate-co-3-hydroxy valerate) (PB) and graphene oxide (GO) have been successfully fabricated by the electrospinning technology. The fabricated scaffolds were examined for their morphological, physical, chemical, piezoelectric, and biological characterizations. The fiber diameter was found to be in the range of 600-800 nm appropriate for chondrogenic growth. Reinforcement of 1.5% GO enhanced the tensile strength of PB to 2.08 ± 0.33 MPa compared to PB alone (0.59 ± 0.12). Reinforcement of GO significantly enhances the piezoelectric coefficient (d33), and for 0.5, 1, and 1.5% GO in PB, it was found to be 0.12 ± 0.015, 0.57 ± 0.19, and 0.94 ± 0.03 pC/N, respectively, and corresponding voltages of 11.84 ± 1.4, 54.69 ± 18.29, and 100.2 ± 3.2 mV, respectively, were generated. The biological activity of the smart piezo scaffolds was also evaluated on freshly isolated goat chondrocytes. The GO-reinforced scaffold showed higher cell proliferation and cell adhesion as confirmed by alamarBlue assay and field emission scanning electron microscopy imaging. The GO-reinforced scaffold has demonstrated significantly higher extracellular matrix production compared to PB as confirmed by histochemistry and real-time polymerase chain reaction. Hence, the GO-based piezoelectric PB electrospun scaffold can be a better alternative for cell-free and growth factor-free approach for cartilage tissue engineering.

Advances in Contrast Agents for Contrast-Enhanced Magnetic Resonance Imaging.

INTRODUCTION: Magnetic resonance imaging (MRI) is a well-established medical invention in modern medical technology diagnosis. It is a nondestructive, versatile, and sensitive technique with a high spatial resolution for medical diagnosis. However, MRI has some limitations in differentiating certain tissues, particularly tiny blood vessels, pathological to healthy tissues, specific tumors, and inflammatory conditions such as arthritis, atherosclerosis, and multiple sclerosis. The contrast agent (CA) assisted imaging is the best possible solution to resolve the limitations of MRI. METHOD: The literature review was carried out using the keywords, "MRI, T1&T2 relaxation, MRI CAs, delivery and adverse effects, classification of CAs." The tools used for the literature search were PubMed, Scopus, and Google Scholar. RESULT AND DISCUSSION: The literature findings focus on MRI technique, limitations, and possible solutions. Primarily, the review focuses on the mechanism of CAs in image formation with detailed explanations of T1 and T2 relaxations, the mechanism of the MRI-CA image formations. This review presents the adverse effects of CA as well as available marketed formulations and recent patents to extent complete information about the MRI-CA. CONCLUSION: MRI generates detailed visual information of various tissues with high resolution and contrast. The proton present in the biological fluid plays a crucial role in MR image formation, and it is unable to distinguish pathological conditions in many cases. The CAs are the best solution to resolve the limitation by interacting with native protons. The present review discusses the mechanism of CAs in contrast enhancement and its broad classification with the latest literature. Furthermore, the article presents information about CA biodistribution and adverse effects. The review concludes with an appropriate solution for adverse effects and presents the future prospective for researchers to develop advanced formulations.

Fast dissolving electrospun polymeric films of anti-diabetic drug repaglinide: formulation and evaluation.

Objective: Repaglinide is a well-known FDA approved drug from category of meglitinide; used for the treatment of diabetes. However, its use is limited because of its poor water solubility which leads to erratic drug absorption. Present work focuses on formulation and evaluation of polyvinyl alcohol (PVA)-polyvinyl pyrrolidone (PVP) nanofibers to counter this problem of poor water solubility.Significance: Prepared nanofibers with hydrophilic polymers were expected to tackle the problem of poor water solubility.Methods: Nanofibers were prepared by electrospinning technique with the optimization of parameters affecting final product. Further prepared formulation was characterized using various techniques.Results: Successful development of drug loaded nanofibers was commenced utilizing electrospinning technique. Further casted film of same polymeric blend was prepared and compared with nanofibers. Optimized nanofibers showed an average diameter of 600-800 nm with smooth surface morphology. Prepared nanofibers and casted film was analyzed in terms of surface morphology, mechanical strength, solid state of drug present, effects of hydrogen bond formation and drug release profile. Results from the glucose tolerance test suggested both the formulations to be having better control over glucose levels as compared to free drug.Conclusion: Overall developed nanofibers presented themselves to be potential drug delivery candidates for drugs having poor water solubility.

Detoxification of poly(methyl methacrylate) bone cement by natural antioxidant intervention.

Poly(methyl methacrylate) (PMMA) bone cement is the most widely used grouting material in the joint arthroplasties and vertebroplasties. The present investigation has been carried out to scavenge the radicals and monomer by addition of an antioxidant to minimize the toxicity of bone cement (BC). The in silico studies were employed to determine the potent natural antioxidant at physiological conditions. The antioxidant methionine demonstrated a strong binding affinity with free radicals and methyl methacrylate (MMA) monomer than cysteine. The designated amount of methionine was optimized by various assay methods and >2% methionine shows strong scavenging capacity in BC. Moreover, the antioxidant-loaded BC (ABC) demonstrated similar handling, physicochemical and mechanical properties to pristine bone cement. Significantly, the developed formulation shows superior biological characteristics such as cell proliferation (2 ± 1 BC and 6 ± 1 ABC), adhesion (0.32 ± 0.02 BC and 0.54 ± 0.01 ABC), and cell viability (81 ± 2% BC and 93 ± 1% ABC) toward human osteoblast-like cells (MG-63). Therefore, the novel antioxidant bone cement is a potential candidate for various orthopedic applications to eliminate the adverse effects, related to residual toxic radical and monomer in bone cement.

Natural fiber reinforced biodegradable staples: Novel approach for efficient wound closure.

Every year millions of lacerations and incisions taken place and require an effective methodology to manage the wound for a better life. The primary causes include mechanical trauma and surgical procedures. The rapid healing of the wound is critical to prevent further infection and reduction pain etc. Current options comprise of sutures, staplers, surgical strips and glues, again the intervention depends on the type of wound and the surgeon preference. The current wound closure techniques pose various potent limitations and confronting the problems to create a desired wound closure technique is necessary for faster and effective wound healing management. The surgical staplers are fast and easy to use wound closure devices, which approximates the edges of the wounds together by staples. The staples are mostly made up of metals like titanium and stainless steel. By modifying the existing stapling method using biodegradable staples that are expected to have good mechanical properties, not require removal procedure, minimized scarring and an overall acceleration in wound healing with minimal complications. Present, the paper focuses on the novel hypothesis on natural fiber reinforced biodegradable polymer staples as wound enclosures with high strength and degradability.

Smart Piezoelectric Nanohybrid of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and Barium Titanate for Stimulated Cartilage Regeneration.

Piezoelectric materials strive to articulate smart materials and transduce electric fields by applying mechanical pressure and vice versa. This study demarcates augmented cartilage regeneration from the praxis of the smart material intervention that denotes the method of the utilized piezoelectric mechanism. The smart piezoelectric nanohybrid is developed from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and barium titanate (BaTiO3). Further, the electrospinning technique is adopted for the scaffolding to mimic the structure of natural cartilage. The scaffold with 20% BaTiO3 shows enhanced mechanical properties and a piezoelectric coefficient (1.4 pC/N) similar to native tissue. Interestingly, the corona poled (electrically polarized) scaffolds demonstrated better cellular activity than unpoled. Human mesenchymal stem-cell-derived chondrocytes are utilized for in vitro studies. The polarized scaffolds highly promote the cell attachment, proliferation, and collagen II gene expression against control (pure PHBV) and unpolarised scaffolds; the effect was quite dominant even in high-piezoelectric-coefficient scaffolds. Therefore, the electric-field-originated scaffolds show the potential effect on cartilage regeneration without the addition of any stimulating molecules.

Piezoelectric smart biomaterials for bone and cartilage tissue engineering.

Tissues like bone and cartilage are remodeled dynamically for their functional requirements by signaling pathways. The signals are controlled by the cells and extracellular matrix and transmitted through an electrical and chemical synapse. Scaffold-based tissue engineering therapies largely disturb the natural signaling pathways, due to their rigidity towards signal conduction, despite their therapeutic advantages. Thus, there is a high need of smart biomaterials, which can conveniently generate and transfer the bioelectric signals analogous to native tissues for appropriate physiological functions. Piezoelectric materials can generate electrical signals in response to the applied stress. Furthermore, they can stimulate the signaling pathways and thereby enhance the tissue regeneration at the impaired site. The piezoelectric scaffolds can act as sensitive mechanoelectrical transduction systems. Hence, it is applicable to the regions, where mechanical loads are predominant. The present review is mainly concentrated on the mechanism related to the electrical stimulation in a biological system and the different piezoelectric materials suitable for bone and cartilage tissue engineering.

Piezoelectric material - A promising approach for bone and cartilage regeneration.

Bone and cartilage are major weight-bearing connective tissues in human and possesses utmost vulnerability for degeneration. The potential causes are mechanical trauma, cancer and disease condition like osteoarthritis and osteoporosis, etc. The regeneration/repair is a challenging, since their complex structures and activities. Current treatment options comprise of auto graft, allograft, artificial bone substituent, autologous chondrocyte implantation, mosaicplasty, marrow stimulation and tissue engineering. Were incompetent to overcome the problem like abandoned growth factor degradation, indistinct growth factor dose and lack of integrity and mechanical properties in regenerated tissues. Present, paper focuses on the novel hypothesis for regeneration of bone and cartilage by using piezoelectric smart property of scaffold material.