Publications

Abstract: Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using in vitro and ex vivo models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue.

Abstract: 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.

Abstract: 

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.

Abstract: 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.

Abstract: Polycystic ovarian syndrome (PCOS) is an endocrinal disorder characterized by multiple tiny cysts, amenorrhea, dysmenorrhea, hirsutism, and infertility. The current diagnostic tools comprise of expensive, time-consuming ultrasonography to serological test, which have low patient compliance. To address these limitations, we have developed a highly sensitive, cost effective and ultrafast immunosensor for the diagnosis of PCOS. Herein, we have fabricated a 2-D electro conductive composites of reduced Graphene oxide (rGO), Molybdenum disulfide (MoS2), and Polyaniline (PANI) as electrode material. Furthermore, for detecting an early and non-cyclic biomarker of PCOS, i.e. anti-Mullerian hormone (AMH). We utilize the specific antigen–antibody mechanism, in which monoclonal Anti-AMH antibodies were covalently immobilized using EDC-NHS chemistry on electrode. The developed biosensor was Physicochemical and electrochemically characterized to demonstrate its efficiency. Further we have investigated the biosensor’s performance with Cyclic Voltammetry, Differential Pulse Voltammetry, and Electrochemical Impedance Spectroscopy. We have validated that under the optimized condition the immunosensor exhibits higher sensitivity with a LOD of ∼ 2.0 ng/mL with a linear range up to 100 ng/mL. Furthermore, this immunosensor works efficiently with a lower sample volume (>5 μL), which provides a sensitive, reproducible, low-cost, rapid analysis to detect AMH level in PCOS diagnosis.

Abstract: The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.

Abstract: Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, the remarkable difficulty in delivering such hydrophobic bioactive molecules prevents further development. To address this critical challenge, we have developed an innovative platform composed of components with a proven track record of safety. We fabricated and thoroughly characterised porous silicon (pSi) microparticles to carry and deliver the natural phenyl propanoid trans-cinnamaldehyde (TC). We investigated its effects on preventing the development of cross-kingdom biofilms (Streptococcus mutans and Candida albicans), typical of dental caries found in children. The prepared pSi microparticles were roughly cubic in structure with 70–75% porosity, to which the TC (pSi-TC) was loaded with about 45% efficiency. The pSi-TC particles exhibited a controlled release of the cargo over a 14-day period. Notably, pSi-TC significantly inhibited biofilms, specifically downregulating the glucan synthesis pathways, leading to reduced adhesion to the substrate. Acid production, a vital virulent trait for caries development, was also hindered by pSi-TC. This pioneering study highlights the potential to develop the novel pSi-TC as a dental caries-preventive material.

Abstract: Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, the remarkable difficulty in delivering such hydrophobic bioactive molecules prevents further development. To address this critical challenge, we have developed an innovative platform composed of components with a proven track record of safety. We fabricated and thoroughly characterised porous silicon (pSi) microparticles to carry and deliver the natural phenyl propanoid trans-cinnamaldehyde (TC). We investigated its effects on preventing the development of cross-kingdom biofilms (Streptococcus mutans and Candida albicans), typical of dental caries found in children. The prepared pSi microparticles were roughly cubic in structure with 70–75% porosity, to which the TC (pSi-TC) was loaded with about 45% efficiency. The pSi-TC particles exhibited a controlled release of the cargo over a 14-day period. Notably, pSi-TC significantly inhibited biofilms, specifically downregulating the glucan synthesis pathways, leading to reduced adhesion to the substrate. Acid production, a vital virulent trait for caries development, was also hindered by pSi-TC. This pioneering study highlights the potential to develop the novel pSi-TC as a dental caries-preventive material.