Intriguingly, 13-mer frog-peptide, temporin L (TempL) contains 50% aromatic residues within its first eight residues. Considering the role of aromatic residues in self-assembly of peptides and the potential of such peptides in biomedical applications, we envisaged to identify new short self-assembling peptides from the amino-terminus of TempL and characterize their structural and biological properties. Thus, starting from the eighth to the first residue of TempL, we synthesized five 4 to 8 residue peptides (T-4mer to T-8mer). Different ultrastructural studies suggested nano-spherical/nano-fibrillar structures of these peptides. Remarkably, T-6mer, T-7mer and T-8mer exhibited polyproline type-II circular dichroism spectra of collagen-like triple-helical structure and sigmoidal melting curves like that we observed with rat-tail type-I collagen. Amazingly, the T-8mer peptide at 1.5% (w/v) forms hydrogel within an hour indicating its ability to form supramolecular assembly, saturated with water. We further studied collagen-mimetic nature of these TempL-derived peptides. HepG2 cells showed significant adhesions onto the coatings of T-6mer, T-7mer, T-8mer peptides and rat-tail type-I collagen which got compromised when these cells were pre-treated with antibody of collagen receptor, integrin α2β1. Interestingly, following the adhesions onto the surface of these TempL-derived peptides, cytoskeletal organization was induced in HepG2 cells like that observed in the presence of a collagen protein. Overall, the current results demonstrated the dissection of a frog-peptide, TempL with revelation of collagen-mimetic peptides from its aromatic-residue rich amino-terminus.

Critical-sized bone defects (CSDs) fail to undergo spontaneous regeneration. Conventional treatment methods, including bone grafts, as well as therapies based on growth factors and cytokines often face serious limitations, including limited availability, immune rejection, high cost, and safety concerns. Although tissue engineering using scaffolds has emerged as a promising alternative, many scaffold-based approaches still rely on the incorporation of exogenous growth factors or cytokines to achieve adequate osteoinductive performance, adding complexity, cost, and potential safety concerns to the treatment. Moreover, invasive implantation techniques and use of toxic crosslinkers during scaffold fabrication present additional challenges. Herein, we report the development of a minimally invasive, injectable, and fully biocompatible hydrogel (CCD@HapSi). The hydrogel, formed via a simple Schiff-base reaction between carboxymethyl chitosan and oxidized dextran, incorporates nanohydroxyapatite and silica nanoparticles to impart osteoinductive, osteoconductive, and antibacterial functionality without the need for external crosslinkers or growth factors. CCD@HapSi exhibited ultrafast gelation, optimal mechanical strength, and controlled degradation, while supporting stem cell adhesion, proliferation, and upregulation of osteogenic genes. In vivo, the hydrogel promoted substantial bone regeneration in a critical sized calvarial defect, significantly outperforming control groups. These findings highlight CCD@HapSi as a safe, cost-effective, and clinically translatable platform for bone regeneration.

Critical-size bone defects remain a major clinical challenge due to the limited regenerative capacity of bone tissue, necessitating biomaterials that provide both structural support and biological stimulation. Synthetic hydroxyapatite (HAp) is widely used for bone repair because of its close similarity to native bone minerals; however, strategies to enhance its biological performance are actively being explored. Among these, ionic substitution-particularly with zinc (Zn2+) and strontium (Sr2+) ions-has emerged as a promising approach to promote osteogenesis while inhibiting bone resorption. Recent studies on Zn/Sr-substituted HAp have reported the formation of undesirable secondary phases, which compromise biological performance. Considering these limitations, the present study aims to synthesize phase-pure Zn- and Sr-substituted hydroxyapatite nanoparticles using a soft-template method, with careful optimization of Zn2+ and Sr2+ concentrations for bone tissue engineering applications. Accordingly, Zn-substituted, Sr-substituted, and Zn/Sr co-substituted hydroxyapatite nanoparticles (Zn-HAp, Sr-HAp, and ZnSr-HAp) were synthesised and systematically characterised. Physicochemical analysis revealed that, in comparison with single-ion substitution, Zn/Sr co-substitution significantly altered crystal nucleation and growth behaviour while preserving phase purity. Biological evaluation using bone-derived cells demonstrated that ZnSr-HAp nanoparticles were highly biocompatible and significantly enhanced cell attachment, proliferation, and matrix mineralisation compared to pristine and single ion-substituted HAp. Furthermore, ZnSr-HAp treatment markedly upregulated the expression of collagen type I (COL I) and osteocalcin (OCN), indicating the promotion of both early extracellular matrix formation and late-stage osteogenic maturation. Collectively, these findings demonstrate a synergistic effect of Zn and Sr co-substitution in enhancing the osteoinductive and osteoconductive properties of HAp. Overall, Zn/Sr co-substituted hydroxyapatite nanoparticles represent a promising bioactive platform for advanced bone regeneration applications.

Collagenases (MMP-1, MMP-8, and MMP-13) play significant roles in the pathophysiology of osteoarthritis. Among these proteins, MMP-13 and MMP-8 are known for their catabolic roles in the degradation of the articular cartilage matrix. Using computational studies, we had previously observed that a metabolite of curcumin, Curcumin monoglucuronide (CMG), binds to MMPs involved in cartilage matrix destruction. The purpose of this study was to confirm the ability of CMG to protect cartilage by blocking the activity of these enzymes. The ability of CMG to bind and block the activities of MMP-13 and MMP-8 was established using several physicochemical methods. First, the protective effect of CMG on MMP-mediated cartilage destruction was demonstrated using cartilage explants in vitro. Second, the in vivo efficacy of CMG was tested by comparison with BI-4394, a specific MMP-13 inhibitor, using a rat anterior cruciate ligament transection (ACLT) model. These studies demonstrated that CMG was more effective than BI-4394 at preventing cartilage degeneration. In separate in vitro studies, CMG did not affect chondrocyte proliferation or the expression of NF-κB-mediated proinflammatory genes. Together, these findings demonstrate the therapeutic potential of CMG and emphasize the importance of inhibiting both MMP-13 and MMP-8 to achieve improved clinical outcomes.

In recent years, smart textile sensors have gained exponential growth in various sectors such as wearable technology and healthcare. However, addressing the demand for wearable textiles that offer both exceptional functionality (e.g., air‐permeability, flexibility) and comfort remains a significant challenge. In this context, a rotary jet‐spun textile piezoelectret is demonstrated, which is not reported so far. The piezoelectric output of the all‐organic textile sensor is improved by 150% in voltage and 200% for current upon electrical poling. The finite element method revealed that the enhanced piezo‐potential is attributed to the trapped polarized charges within the piezoelectret matrix. It exhibited outstanding piezoelectric properties with sensitivity of 400 mV kPa −1 (pressure range, 0.6–7 kPa), waterproofness (water contact angle ≈134°) and high breathability (10 kg m −2 per day), ensuring wearer comfort. Apart from monitoring different physiological signals such as pulse and respiratory rate, it also acted as a sensor array that displays the deep learning‐aided pressure mapping with the accuracy of 98%. In addition, this textile accelerated faster proliferation and migration of L929 cell due to its piezoelectricity induced electrical stimulation, suggesting its potential application in wound dressings. Thus, this approach has huge potential to offer a scalable and versatile solution for biomedical technology.

A growing antimicrobial crisis has increased demand for antimicrobial materials. It has become increasingly popular to convert polymeric macromolecules into polymeric carbon particles (PCP) in order to achieve highly biocompatible materials with unique properties as a result of the ability to synthesize nanomaterials of the right size and add value to existing stable polymers. This work presents the tuning of PCP for antibacterial application by combining a biocidal polymer with one-pot solvothermal synthesis. PCP displayed broad-spectrum antibacterial activity via various mechanisms, including inhibition of bacterial cell walls, ROS generation, and antibiotic resistance. Furthermore, these biocidal PCP were observed to show excitation-independent near-white light emission which on the other hand is generally possible due to mixed sizes, doping, and surface effects. As opposed to the parent biocidal polymer, PCP added ROS-mediated bactericidal activity, increased cytocompatibility, and nanofibers with anti-adhesive effects and potential of imaging bacterial cells.

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Release of BI-4394, a MMP-13 inhibitor, from an enzyme-responsive hydrogel protects cartilage from progressive degeneration in an ACLT rat model.

The development of engineered nanomaterials has been considered a promising strategy to control oral infections. In this study, silver-embedded carbon nitrides (Ag@g-CN) were synthesized and tested against Candida albicans, investigating their antifungal action and biocompatibility in animal cells. Ag@g-CN was synthesized by a simple one-pot thermal polymerization technique and characterized by various analytical techniques. X-ray diffraction (XRD) analysis revealed slight alterations in the crystal structure of g-CN upon the incorporation of Ag. Fourier transform infrared (FT-IR) spectroscopy confirmed the presence of Ag-N bonds, indicating successful silver incorporation and potential interactions with g-CN's amino groups. UV-vis spectroscopy demonstrated a red shift in the absorption edge of Ag@g-CN compared with g-CN, attributed to the surface plasmon resonance effect of silver nanoparticles. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) confirmed the 2D layered sheet like morphology of both materials. The Ag 3d peaks found in X-ray photoelectron spectroscopy (XPS) confirmed the presence of metallic Ag-0 nanoparticles in Ag@g-CN. The Ag@g-CN materials exhibited high antifungal activity against reference and oral clinical strains of C. albicans, with minimal inhibitory concentration (MIC) ranges between 16-256 mu g/mL. The mechanism of Ag@g-CN on C. albicans was attributed to the disruption of the membrane integrity and disturbance of the biofilm. In addition, the Ag@g-CN material showed good biocompatibility in the fibroblastic cell line and in Galleria mellonella, with no apparent cytotoxicity observed at a concentration up to 1000 mu g/mL. These findings demonstrate the potential of the Ag@g-CN material as an effective and safe antifungal agent for the treatment of oral fungal infections.

Objectives: The increasing incidence of chronic wounds such as diabetic foot ulcers and pressure ulcers, often compounded by bacterial infections and biofilm formation, presents significant challenges in wound management. Despite advancements in wound care products and a better understanding of molecular wound repair mechanisms, the treatment of chronic ulcerating conditions remains incomplete. VG111, a novel natural product formulation, emerges as a promising therapeutic candidate addressing the need for an effective wound healing agent with antimicrobial and tissue regenerative properties. Materials and Methods: A thorough evaluation of VG111 included antimicrobial assays to determine its minimum inhibitory concentration against an array of pathogens, assessment of its biofilm disruption capabilities, investigation into its profibrogenic activity through scratch assays, and analysis of its immunomodulatory effects on macrophage-derived cytokines. Quality consistency was ensured by high-performance liquid chromatography fingerprinting, while clinical applicability was assessed through observations in canine and human wound healing cases. Statistical Analysis: The cytotoxic effects of VG111 were assessed using a Two-way ANOVA, indicating no significant cytotoxicity at the tested concentration (Column factor p<0.0001). Results: VG111 demonstrated potent antimicrobial action with effective concentrations ranging from 2.5% to 5.0% v/v, targeting resistant strains of Methicillin-resistant Staphylococcus aureus , colistin-resistant Escherichia coli, Acinetobacter baumannii , and other priority pathogens. It showed biofilm clearance, enhanced fibroblast migration, and a favorable immunomodulatory profile by reducing inflammatory cytokines in vitro. In vivo applications corroborated these findings, with significant wound healing observed in both veterinary and clinical settings, negating the need for additional antibiotics. Conclusions: The study emphasized on VG111 as a robust wound healing agent with significant antimicrobial and biofilm-disrupting properties. Its broad-spectrum efficacy against critical pathogens and ability to promote tissue regeneration mark it as a promising avenue in the management of complex chronic wounds, meriting further clinical exploration.

Sesamol, a lignan, obtained from sesame seeds (Sesamum indicum Linn., Pedaliaciae) has a promising antioxidant, and anti-inflammatory profile. When applied topically, free sesamol rapidly crosses skin layers and gets absorbed in systemic circulation. Its encapsulation into solid lipid nanoparticles not only improved its localised delivery to skin but also resulted in better skin retention, as found in ex-vivo skin retention studies. Free and encapsulated sesamol was compared for antimicrobial and antibiofilm activity against some common skin pathogens and it was found that encapsulation improved the antimicrobial profile by 200%. In vivo evaluation in diabetic open excision wound model suggested that encapsulation of sesamol in SLNs substantially enhanced its wound healing potential when investigated for biophysical, biochemical and histological parameters. It was envisaged that this was achieved via inhibiting bacterial growth and clearing the bacterial biofilm at the wound site, and by regulating oxidative stress in skin tissue.

Hematein, the oxidized form of hematoxylin, is extensively used in laboratories for cell identification. Despite its known adverse effects on the environment, there is currently no standardized method for hematein treatment. With the objective of developing a simplified approach for hematein degradation at the point of use, we evaluated the photocatalytic performance of the as-prepared polymeric graphitic carbon nitride (C3N4). The formation of exfoliated C3N4 (E-C3N4) was confirmed through the observation of reduced sheet thickness, increased surface area, and a modified band gap. E-C3N4 exhibited a higher degradation rate compared to bulk C3N4 under solar irradiation owing to the lower charge transfer resistance and improved charge separation. Transient absorption spectroscopy revealed that the hot electrons of E-C3N4 readily transfer to the photoactive sites and efficiently facilitate hematein degradation. Additionally, we also noted the degradation of hematein occurring through an exciton-mediated energy transfer pathway. The catalytic performance appeared to improve with an increase in the catalyst concentration. Notably, E-C3N4 demonstrated consistent degradation performance over five cycles. Our results confirm that hematein can be repeatedly degraded in the laboratory using the biocompatible E-C3N4, and the byproducts generated during hematein degradation were found to be biocompatible. This study represents a step toward developing an environmentally friendly and efficient method for hematein treatment in laboratory settings.

Chronic exuding wounds continue to present a significant healthcare challenge, with prolonged healing times and an increased risk of complications. The wounds with their complex contours and hard-to-reach areas, can particularly benefit from the advantages offered by free-flowing hydrogel particles. Innovative approaches are needed to enhance the healing process and improve outcomes in wound care. Building upon previous research on piezo-driven electrical stimulation, herein, we introduce self-powered, silver nanoparticles containing electroactive hydrogel particles as an innovative wound dressing specifically designed to fill deep irregular wound cavities. Apart from providing anti-bacterial and a moist wound environment, the hydrogel particles provide electrical stimulation to the wound-bed. The self-powered dressing eliminates the need for an external power source by harnessing the electrical activity from a piezo-responsive polyvinylidene fluoride (PVDF) membrane, thereby improving patient compliance. The electroactive hydrogel particles exhibited improved cellular responses including cell migration, proliferation and angiogenesis. Accelerated wound closure, increase in collagen synthesis and improvement in angiogenesis was observed in rats treated with the dressing. By elucidating the mechanisms and benefits of this innovative approach, we seek to highlight its potential as an effective and practical solution for the treatment of challenging wounds.

Sunlight driven strontium doped tin oxide (SnO2) photocatalyst was synthesized with different strontium (Sr) concentrations by the simplest sol-gel methodology. The XRD diffractogram findings revealed the decrement in the average crystallite size from 13 nm to 8 nm and shifting of diffraction peaks towards lower diffraction angle signifies the incorporation of Sr2+ ions in the host lattice sites. Optical studies unveiled the reduction in the energy bandgap values with respect to doping concentration i.e. 2.94 eV for pristine SnO2 to 2.43 eV for 1.5% Sr:SnO2. The photocatalytic measurements showed that the action of Sr doped SnO2 nanoparticles (1.5%) on methylene blue (MB) and crystal violet (CV) dyes exhibited momentous photocatalytic performance of about 83.3% in 100 minutes and 67.8% in 150 minutes under natural sunlight. Additionally, an efficient antibacterial activity of Sr doped SnO2 nanoparticles (at 1.5% doping) was estimated against a gram negative bacteria E. Coli.

Interest in the development of new generation injectable bone cements having appropriate mechanical properties, biodegradability, and bioactivity has been rekindled with the advent of nanoscience. Injectable bone cements made with calcium sulfate (CS) are of significant interest, owing to its compatibility and optimal self-setting property. Its rapid resorption rate, lack of bioactivity, and poor mechanical strength serve as a deterrent for its wide application. Herein, a significantly improved CS-based injectable bone cement (modified calcium sulfate termed as CSmod ), reinforced with various concentrations (0-15%) of a conductive nanocomposite containing gold nanodots and nanohydroxyapatite decorated reduced graphene oxide (rGO) sheets (AuHp@rGO), and functionalized with vancomycin, is presented. The piezo-responsive cement exhibits favorable injectability and setting times, along with improved mechanical properties. The antimicrobial, osteoinductive, and osteoconductive properties of the CSmod cement are confirmed using appropriate in vitro studies. There is an upregulation of the paracrine signaling mediated crosstalk between mesenchymal stem cells and human umbilical vein endothelial cells seeded on these cements. The ability of CSmod to induce endothelial cell recruitment and augment bone regeneration is evidenced in relevant rat models. The results imply that the multipronged activity exhibited by the novel-CSmod cement would be beneficial for bone repair.

VG111, a novel natural product formulation developed at PGIMER, Chandigarh is an attempt to meet the requirements of an ideal wound healing product. The present study demonstrates the efficacy of VG111 in antimicrobial assay, in tissue-regeneration,and in direct application-based wound healing. VG111 was able to kill major human pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, carbapenem-resistant Acinetobacter baumannii (CRAB), while biofilm clearance was observed for Pseudomonas aeruginosa PA14 and Stenotrophomonas sepilia. Scratch assay and cytokine estimation in VG111-treated RAW464.7 cell lines show that it enhances cell migration and limits host inflammatory response by lowering IL-6 and TNF-α levels. VG111 application in canine and human patients’ representative cases provides evidence of remarkable wound healing and improved recovery. In particular, its potential to treat aggravated wounds in diabetic patients without the need of administering additional antibiotics in patients on steroids and obviating the need of skin graft adds on to make this natural product formulation to be a game-changer in the segment.

Injectablehydrogels have demonstrated advantages in cartilagerepair by enabling the delivery of cells through a minimally invasiveapproach. However, several injectable hydrogels suffer from rapiddegradation and low mechanical strength. Moreover, higher mechanicalstiffness in hydrogels can have a detrimental effect on post-implantationcell viability. To address these challenges, we developed an in situforming bioinspired double network hydrogel (BDNH) that exhibits temperature-dependentstiffening after implantation. The BDNH mimics the microarchitectureof aggrecan, with hyaluronic acid-conjugated poly(N-isopropylacrylamide) providing rigidity and Schiff base crosslinkedpolymers serving as the ductile counterpart. BDNHs exhibited self-healingproperty and enhanced stiffness at physiological temperature. Excellentcell viability, long time cell proliferation, and cartilage specificmatrix production were observed in the chondrocytes cultured in theBDNH hydrogel. Evidence of cartilage regeneration in a rabbit cartilagedefect model using chondrocyte-laden BDNH has suggested it to be apotential candidate for cartilage tissue engineering.

Hydrogels are widely recognized and favoured as moist wound dressings due to their beneficial properties. However, their limited capacity to absorb fluids restricts their use in highly exuding wounds. Microgels are small sized hydrogels that have recently gained considerable attention in drug delivery applications due to their superior swelling behaviour and ease of application. In this study, we introduce dehydrated microgel particles (μGeld) that rapidly swell and interconnect, forming an integrated hydrogel when exposed to fluid. These free-flowing microgel particles, derived from the interaction of carboxymethylated forms of starch and cellulose, have been designed to significantly absorb fluid and release silver nanoparticles in order to effectively control infection. Studies using simulated wound models validated the microgels ability to efficiently regulate the wound exudate and create a moist environment. While the biocompatibility and hemocompatibility studies confirmed the safety of the μGel particles, its haemostatic property was established using relevant models. Furthermore, the promising results from a full-thickness wounds in rats have highlighted the enhanced healing potential of the microgel particles. These findings suggest that the dehydrated microgels can evolve as a new class of smart wound dressings.