Devadass Jessy Mercy

Wound healing is the critical process regulated through a harmonious coordination of cellular, molecular, pathological, and systemic communications. Normally, healing occurs in four overlapping phases, which are modified and controlled by various growth factor interactions and signaling pathways. Disruption of the tightly coordinated wound‐healing cascade, together with aberrant protein signaling, mitochondrial dysfunction, antimicrobial resistance, sustained fibroblast activation, and maladaptive epigenetic reprogramming, drives pathological tissue repair culminating in chronic non‐healing wounds, including diabetic, ischemic, and venous ulcers, as well as fibrotic outcomes such as hypertrophic and keloid scarring. The persistent fibroblast activation, reduced apoptosis, prolonged TGF‐β activity, and severe fibrosis induced by mechanical methods trigger excessive healing, while existing therapies fail to manage these functions. Therefore, in order to develop advancements toward precise and personalized medicine, it is important to understand the various mechanisms involved in wound healing. The current review provides a comprehensive understanding of various fundamental mechanisms involved in wound healing, such as cellular, molecular, signaling pathways, genetic, epigenetic, pathological, immunological, and systemic mechanisms. Knowledge of these mechanisms and how they work under physiological as well as pathological conditions connects to clinical inefficiency, which helps to provide accurate medicine. A deeper mechanistic knowledge paves the way for developing innovative biomaterials; nanotechnology‐based therapeutic strategies, specific drug delivery, molecular biomarkers, and scar‐free healing of wounds, which enrich the future with advanced therapeutics and personalized medicine for wounds.

Background and purpose: Protein misfolding and subsequent amyloid formation are associated with various diseases like localized amyloidosis, type II diabetes, and other neurodegenerative diseases. Insulin can undergo fibrillation under specific physiological conditions, leading to the formation of localized amyloid deposits. Repeated subcutaneous administration of insulin fibrils induces amyloid mass at injection sites. Experimental approach: This study investigated the pathological consequences of insulin fibril deposition in a rat model and evaluated the anti-amyloid efficacy of iota-carrageenan (CG) and its liposomal nano­formulation (nCG). Repeated subcutaneous administration of insulin for 28 days induced the formation of a well-defined amyloid mass. Key results: Treatment with nCG markedly reduced amyloid accumulation and effectively suppressed amyloid progression. Histopathological examination demonstrated a concentration-dependent reduction in amyloid deposits following CG treatment, while nCG-treated groups exhibited no detectable amyloid accumulation. The formation and inhibition of amyloid were further validated by hematoxylin and eosin (H&E), Congo red and thioflavin T (ThT) staining. In addition, nCG showed excellent biocompatibility, with no observable pathological alterations in major organs. Conclusion: Collectively, these findings indicate that both CG and nCG possess significant anti-amyloid activity, with nanoformulated CG showing enhanced efficacy in preventing insulin-induced localized amyloidosis.

Background/objectives: Delayed wound healing, along with excessive scar formation, is the major clinical drawback due to the presence of stubborn bacteria, oxidative stress, prolonged inflammation, and irregular tissue regeneration. Utilizing nanomaterial-based wound dressings offers significant advancements and minimal cytotoxicity, but also presents issues such as poor biocompatibility, low solubility, and reduced permeability. These factors limit the effectiveness of nanomaterial-based wound dressings in promoting complete tissue regeneration. To overcome these limitations, plant-derived bioactives are integrated with nanomaterials within a hydrogel cage to enhance antibacterial activity, mitigate oxidative stress and inflammation, and promote tissue regeneration. Methods: A multifunctional alginate–gelatin hydrogel incorporating silver nanoparticles and plant extracts (AG-AgNP-PE) was developed to promote scar-free wound healing, alongside a plant extract-free silver nanoparticles-loaded hydrogel for comparative evaluation of the functional contribution of plant bioactives. The biological performance of the formulated hydrogels was systematically evaluated through antioxidant, antimicrobial, and antibiofilm assays, while in vitro cytocompatibility and proregenerative activity were assessed using MTT and Alamar Blue assays, live/dead cell imaging, and a scratch-wound assay, complemented by in vivo evaluation in zebrafish embryos. Results: Pro-angiogenic activity was further investigated using the CAM model, and therapeutic efficacy was validated in an in vivo rat burn wound model through microscopic wound assessment, histopathological examination, and biochemical assays. Conclusions: Among the hydrogels, AG-AgNP-PE exhibited superior performance across all key properties, highlighting the synergistic effect of the nanomaterial combined with plant extracts within hydrogel cages and positioning it as a promising multifunctional wound dressing for rapid tissue regeneration and scar-free wound healing, suitable for advanced wound management.

The field of nanotechnology has witnessed a paradigm shift towards eco-friendly and sustainable synthesis methods for nanoparticles due to increasing concerns over environmental toxicity and resource sustainability. Among various metal oxide nanoparticles, zirconium dioxide (ZrO₂) nanoparticles have garnered significant attention owing to their exceptional thermal stability, biocompatibility, mechanical strength, and catalytic properties. Doping ZrO₂ with transition metals such as copper (Cu) further enhances its physicochemical attributes, including antibacterial activity, redox behaviour, and electronic properties, rendering it suitable for a diverse range of biomedical and industrial applications. In the present study, we report the green synthesis of copper-doped ZrO₂ nanoparticles (Cu-ZrO₂-CO NPs) using an aqueous extract of Calendula officinalis (marigold) flowers as a natural reducing and stabilizing agent. The complete characterization was performed using UV–vis spectrophotometry, dynamic light scattering (DLS), zeta potential, FTIR, SEM, EDAX, and XRD, revealing its size to be around 20–40 nm and zeta potential as −20 mV, indicating nano size and stability. The biocompatibility of the as-synthesized nanoparticle was analyzed in vitro using fibroblast cell viability and haemolysis assay, and in vivo using brine shrimp assay. The nanoparticles were safe up to a dose of 50 μg/mL, showing more than 95% cell viability and less than 2% haemolysis, which is within an acceptable range. Finally, the anticancer activity was explored for A549 cells by MTT assay and live-dead assay, with an IC50 value of 38.63 μg/mL. The chorioallantoic membrane (CAM) model was used to assess the anti-angiogenesis potential of the Cu-ZrO₂-CO NPs. The results showed that the nanoparticles could kill the cancer cells via apoptosis, and one of the reasons for the anticancer effect was angiogenesis inhibition. Further research is needed using other cancer cell lines and animal tumour models.

The emergence of anti-microbial resistance (AMR) has become a pressing need for the design of novel and potential anti-microbial and anti-biofilm agents. Nano-scaled materials have been designed in the research domain to curb the populous spread of microbial biofilms. In the context of nano-scaled materials, metal nanoparticles are of unique importance and have been studied in detail for the treatment of biofilm propagation and menace. The crucial aspects of metal nanoparticles and their complexation with graphene have been extensively understood at the molecular level in this review article. The molecular interplay between the various external stimuli, like pH, temperature, sound, mechanical stimuli, and different external factors, on biofilm regulation has been studied and accentuated in the paper. The effect of such external factors succumbing to the biofilm-producing microbes, to the potential inhibitory activities of such novel nano-composites has been unraveled in the present review. Understanding the methodology behind nanoscaled treatments and their molecular mechanisms could pave the way for novel biofilm targeting strategies.

Masking drugs by entrapping them in the immune-evasive materials facilitates targeted delivery to specific parts of the body. Cancers, including lung cancer and ascitic tumors, remain significant threats to human life, with limited effective treatment options. In the present study, to specifically target lung cancer and Dalton’s lymphoma ascitic (DLA) cells, we synthesized green silver nanoparticles (NS-AgNps) using Nigella sativa (NS) seeds extract, with thymoquinone as the reducing and capping agent, confirmed by GC–MS analysis. The nanoparticles were characterized through various photophysical techniques at different stages of fabrication. Lactobacillus spp., isolated from prebiotic and probiotic tablets and identified through biochemical tests, were coated with synthesized NS-AgNps to form lactobacillus coated-Nigella sativa-silver nanoparticles (L-NS-AgNps). The successful coating was confirmed by scanning electron microscopy. The anticancer activity of L-NS-AgNps was evaluated against A549 (human lung carcinoma cells) and DLA cells using MTT and Trypan blue assays. L-NS-AgNPs exhibited dose-dependent cytotoxicity with a maximum of 54% cell death at 3 µg/ml and an LC50 of 3.005 µg/ml for A549 cells, and 58% cell death in DLA cells. Biocompatibility was assessed both in vitro and in vivo using fibroblast cell lines (V79) and zebrafish embryos, respectively. The nanoparticles showed high biocompatibility, maintaining over 95% viability in V79 fibroblasts and causing no developmental abnormalities in zebrafish embryos at a concentration up to 3 µg/ml. These findings suggest that our L-NS-AgNPs hold strong potential as a novel and safe therapeutic agent for cancer treatment.

Angiogenesis plays a pivotal role in the survival of cancer tumors, and any agent that can inhibit angiogenesis can be categorized as an efficient anticancer agent. In the present study, the synergistic anticancer effect of Cerium oxide nanoparticles (CeO₂) and Doxorubicin (Dox) encased in a polymeric nano matrix of chitosan and alginate (Alg@Cs@CeO₂‐Dox) is investigated. The product inhibits the cell migration of skin cancer cells (A375), and lung cancer cells (A549) and exhibits anti‐angiogenesis in the in‐ovo model with reduced blood vessel formation. Melanoma is induced in Swiss albino mice, and the anticancer effect is evident in two different concentrations of Alg@Cs@CeO₂‐Dox for 21 days. After treatment, the histopathological analysis of the cancer section tissue shows that the Alg@Cs@CeO₂‐Dox completely neutralizes the melanoma symptoms in the animal. After the analysis, it is presumed that the combination of CeO₂ and Dox encased in polymeric nano matrix demonstrates a higher therapeutic effect in cancer cells and animals than the individual drugs. Further, the study can be extrapolated in other cancer models in animals.

Developing an effective vaccine that is safer is the main focus in the field of cancer immunotherapy. Among other therapeutic approaches, cancer nanovaccination is formulated to deliver tumor adjuvant or antigen to the antigen-presenting cells (APCs) to prevent cancer relapse and metastasis. It has shown excellent efficacy in inhibiting cancer growth. Herein, we discussed various forms of nanovaccines, including lipid-based nanovaccines, metal-based nanovaccines, carbon nanotube-based nanovaccines, PLGA-based nanovaccines, exosome-based nanovaccines, dendritic cell-based nanovaccines, and self-adjuvant nanovaccines in cancer immunotherapy, including their therapeutic effect. We expect that the investigated content will provide a valuable reference for future research and the development of nanovaccines for cancer treatment.

Skin cancer is diagnosed usually at the last stage and the available conventional treatments are costly and have various side‐effects. It is therefore necessary to design a biocompatible alternative treatment approach. In our present study, the liposomal formulation of marine red algae Amphiroa anceps is investigated for its anticancer activity against skin cancer. The aqueous extract (HA) and the liposomal formulated aqueous extract (NHA) of A. anceps are characterized using Raman spectroscopy, high‐performance liquid chromatography (HPLC) and scanning electron microscopy (SEM). SEM reveals the size of NHA to be around 150–230 nm. In HPLC, two prominent peaks at the retention time of 5.233 min and 5.775 min are observed. NHA exhibits anticancer activity in skin cancer cells (A375) dose‐dependently, and the cell viability 100 µg/mL is 16% ± 2%. The in vitro biocompatibility assays using fibroblast cell viability and haemolysis assay, show that the NHA is safe and highly biocompatible. A step forward, the Chorioallantoic Membrane Assay assay reveals HA and NHA have anti‐angiogenesis activity. Our study elucidates that NHA induces anticancer activity by cell necrosis and reducing new blood vessel formation, and can be a safe and promising therapeutic agent for cancer management.