Controlling the orientation of the polymeric networks is of significant interest in developing hydrogel-based tissue-engineering platforms. Herein, a model system, smartly passivated carbon nanoparticles (smapCNPs) enforced PNIPAM hydrogel, revealed the role of smapCNPs in the formation of a temporally efficient phase-separated-meshwork (PhaseDMesh). Intriguingly, such a PhaseDMesh was morphologically alternative to the meshwork induced by extracellularly relevant salts like NaCl and KCl. Further investigations on PhaseDMesh demonstrated its ability to support the attachment, growth, and differentiation of myoblasts under simulated salt-imbalanced conditions. Therefore, suitably incorporated smapCNPs could be a functional alternative to extracellular salt ions in generating hydrogel platforms for muscle tissue-engineering.

An injectable hydrogel hemostat composed of bacterial cellulose (BC), polydopamine and carboxymethyl cellulose (CMC) is presented as a biocompatible alternative to generally cytotoxic commercial hemostats.

This work reveals the strategy of in situ carbonization and biological application of carbonized porous silica particles (Si-P-CNPs) which improved the biodegradability and lesser fibrosis induction, demonstrating the importance of this process.

The emergence of multidrug resistance in cancer cells necessitates the development of new therapeutic modalities. One way cancer cells orchestrate energy metabolism and redox homeostasis is through overloaded iron pools directed by iron regulatory proteins, including transferrin. Here, we demonstrate that targeting redox homeostasis using nitrogen -based heterocyclic iron chelators and their iron complexes efficiently prevents the proliferation of liver cancer cells (EC 50 : 340 nM for IITK4003) and liver cancer 3D spheroids. These iron complexes generate highly reactive Fe(IV)=O species and accumulate lipid peroxides to promote oxidative stress in cells that impair mitochondrial function. Subsequent leakage of mitochondrial cytochrome c activates the caspase cascade to trigger the intrinsic apoptosis pathway in cancer cells. This strategy could be applied to leverage the inherent iron overload in cancer cells to selectively promote intrinsic cellular apoptosis for the development of unique iron -complex -based anticancer therapeutics.

In the pursuit to combat stubborn bacterial infections, particularly those stemming from gram-positive bacteria, this study is an attempt to craft a precision-driven platform characterized by unparalleled selectivity, specificity, and synergistic antimicrobial mechanisms. Leveraging remarkable potential of metalloantibiotics in antimicrobial applications, herein, this work rationally designs, synthesizes, and characterizes a new library of Pyridine-2,6-dicarboxamide ligands and their corresponding transition metal Cu(II)/Zn(II) complexes. The lead compound L11 demonstrates robust antibacterial properties against Staphylococcus aureus (Minimum Inhibitory Concentration (MIC) = 2-16 µg mL-1), methicillin and vancomycin-resistant S. aureus (MIC = 2-4 µg mL-1) and exhibit superior antibacterial activity when compared to FDA-approved vancomycin, the drug of last resort. Additionally, the compound exhibits notable antimicrobial efficacy against resistant enterococcus strains (MIC = 2-8 µg mL-1). To unravel mechanistic profile, advanced imaging techniques including SEM and AFM are harnessed, collectively suggesting a mechanistic pathway involving cell wall disruption. Live/dead fluorescence studies further confirm efficacy of L11 and its complexes against S. aureus membranes. This translational exploration extends to a rat model, indicating promising in vivo therapeutic potential. Thus, this comprehensive research initiative has capabilities to transcends the confines of this laboratory, heralding a pivotal step toward combatting antibiotic-resistant pathogens and advancing the frontiers of metalloantibiotics-based therapy with a profound clinical implication.

Polymer carbon composites have been reported for improved mechanical, thermal and electrical properties to provide reduced side effect by 3D printing personalized biomedical drug delivery devices. But control on homogeneity in loading and release of dopants like carbon allotropes and drugs, respectively, in the bulk and on the surface has always been a challenge. Herein, we are reporting a methodological cascade to achieve a model, customizable, 3D printed, homogeneously layered and electrically stimulatory, PLA-Graphene nanoplatelet (hl-PLGR) based drug delivery device, called 3D-est-MediPatch. The medicinal patch has been prepared by 3D-printing a Nic-hl-PLGR composite obtained by incorporating a redox active model drug, niclosamide (Nic) in hl-PLGR. The composite of Nic-hl-PLGR was characterized in three sequentially complex forms─composite film, hot melt extruded (HME) filament, and 3D printed (3DP) patches to understand the effect of filament extrusion and 3D-printing processes on Nic-hl-PLGR composite and overall drug incorporation efficiency and control. The incorporation of graphene was found to improve the homogeneity of the drug, and the hot melt extrusion improved the dispersion of drug and graphene fillers in the composite. The electroresponsive drug release from the Nic-hl-PLGR composite was found to be controllably accelerated compared to the drug release by diffusion, in simulated buffer condition. The released drug concentration was found to reach within the IC50 range for malignant melanoma cell (A375) and showed in vitro selectively, with reduced effects in noncancerous, fibroblast cells (NIH3T3). Further, the feasibility of application for this system was assessed in generating personalized 3D-est-MediPatch for skin, liver and spleen tissues in ex-vivo scenario. It showed excellent feasibility and efficacy of the 3D-est-MediPatch in controlled and personalized release of drugs during electrostimulation. Thus, a model platform, 3D-est-MediPatch, could be achieved by suitably incorporating a hydrophobic, redox-active drug (niclosamide) in poly lactic acid-graphene nanoplatelet composite for electrostimulatory therapeutics with reduced side effects.

Mechanical damages to skeletal muscles could be detrimental to the active work hours and lifestyle of athletes, mountaineers, and security personnel. In this regard, the slowness of conventional treatment strategies and drug-associated side effects greatly demand the design and development of novel biomaterials, which can rescue such mechanically damaged skeletal muscles. To accomplish this demand, we have developed a musculoresponsive polymer-carbon composite for assisting myotubular regeneration (MusCAMLR). The MusCAMLR is enforced to attain anisotropic muscle-like characteristics while incorporating a smartly passivated nanoscale carbon material in the PNIPAM gel under physiological conditions as a stimulus, which is not achieved by the pristine nanocarbon system. The MusCAMLR establishes a specific mechanical interaction with muscle cells, supports myotube regeneration, maintains excellent mechanical similarity with the myotube, and restores the structural integrity and biochemical parameters of mechanically damaged muscles in a delayed onset muscle soreness (DOMS) rat model within a short period of 72 h. Concisely, this study discloses the potential of smartly passivated nanocarbon in generating an advanced biomaterial system, MusCAMLR, from a regularly used polymeric hydrogel system. This engineered polymer-carbon composite reveals its possible potential to be used as a nondrug therapeutic alternative for rescuing mechanically damaged muscles and probably can be extended for therapy of various other diseases including muscular dystrophy.

The evolution of lipid nanoparticles (LNPs) has been remarkably interesting and in beneficent directions for food and health industries working towards human well being. Since the discovery of the first-generation lipid based self-assembled nanostructures, i.e., liposomes in the 1960s, it has witnessed significant advances in their development and distinctive potential in different application domains. Based on the composition and structure, these lipid-based structures have varied from liposome to lipid nanoparticles, e.g., solid lipid nanoparticles (SLNs) & nanostructured lipid carriers (NLCs) to overcome certain limitation pertaining to their use in different fields. The outstanding application of LNP5 as therapeutic delivery systems has made them key players to treat different human disorders including the fatal cancers. Their life-saving global contribution has recently been witnessed in the form of mRNA vaccines against deadly COVID-19. They have also significantly served purpose in other domains such as biomedical imaging, cosmetics, nutrition, and agriculture. Their prominent role is in the area of anticancer therapy as delivery vectors for nucleic acids and drugs. Some issues with respect to the cellular delivery of drugs and genes, such as circulation time and stability have been somewhat resolved, but the unmet goal of site-specific substantial delivery remains the main focus in LNP5 development research. Despite the promise shown by LNP5 in animal studies and the fact that technological advances in LNP5 research have made the approval possible of a few formulations, therapeutic outcomes in human are not satisfactory. The LNP5 technology has managed to survive due to possible tailoring of their properties by virtue of the possibility of altering the composition and modifying the surface. Therefore, enormous scientific endeavours are on the rise to transform lipid structures, composition along with tinkering with surface of LNP5. The alternative methods to guide LNP5 coupled with advances in small molecule nucleic acid therapeutics and drug development technology to make the entry possible to specific cells may be effective in cancer therapy. The development is very promising; however enduring efforts are required till the goal is reached.

The phenotype of the donor thymocytes present in the thymus of irradiated mice injected intravenously with CD3-depleted total bone marrow cells has been studied by three-color flow cytometry during the time period 6-16 days postinjection. Donor cells could first be reliably detected at Day 6 after reconstitution. Donor and host cells maintain their relative proportions over the first few days, after which time the proportion of donor cells derived from the bone marrow increases. At Days 6 and 7 after reconstitution, Pgp-1+, IL-2R- cells predominate, although a minority of Pgp-1+, IL-2R+ cells is also seen. Few cells are Pgp-1-, IL-2R+. Over the next 3 days, the relative proportion of Pgp-1+, IL-2R- cells declines rapidly and the relative proportion of Pgp-1+, IL-2R+ cells and then of Pgp-1-, IL-2R+ cells peaks and declines. The absolute number of all three populations, however, increases exponentially until Day 14. Most donor cells present at Days 6-7 after reconstitution are L3T4-, Lyt-2-. Over the next 2 days, the majority of donor-derived cells express low, but significant, levels of both L3T4 and Lyt-2. L3T4+, Lyt-2+ cells expressing levels of cell surface antigen characteristic of the cognate population found in the adult first appear at Day 10 after reconstitution. These L3T4+, Lyt-2+ donor cells increase in proportion to reach 70-80% of donor-derived cells after Day 14 of reconstitution. The host thymocyte population, on the other hand, contains few Pgp-1+ or IL-2R+ cells even at 7 days after irradiation and is predominantly L3T4+, Lyt-2+ by Day 8. This observation suggests that the host cells are derived from a more mature precursor than the bone marrow prothymocyte or the earliest intrathymic progenitors.

Biomaterials have been designed to interact with biological systems to aid wound healing, regeneration of tissue, provide mechanical support and drug delivery to eventually improve current therapeutic outcomes. The adoption of biomaterials is increasing constantly in health care practices by making it more biocompatible and non-toxic under physiological condition. These adoptions have been associated with improvements in therapeutic outcomes across the population, however, the dosage of therapeutics needed to successfully treat a disease is generally different for each individual and relies on a lot on experiences of consultant doctors. This might lead to human errors in deciding drug doses and un-fit implants or explants and eventually adverse or less positive effects. The personalized medicine and devices bring forth the idea that the medicine should be tailored for a patient based on various characteristics, such as gender, age, genetic makeup and lifestyle. Use of these personalized medicine approaches include deciding on type of drugs, their activation methods and application as nano-assemblies or biomedical devices, etc. Among these approaches, personalized biomedical devices have become popular with the advent of 3D printing technologies, which can make customized implants for each patient with minimum price, limited time and high accuracy. Personalized biomedicine also involves designing of drug to cater the need of an individual with minimum side effects. In this book article, an effort has been made to introduce the reader to the different aspects of customized biomedical agents like therapeutic biomolecules, nanomedicine, implants, and explants. This comprehensive book article of literature indicates that use of 3D printing technology in producing drug releasing, biodegradable personalized implants could be better therapeutic solutions to range of medical conditions.

Carbon materials are generally utilized in the form of carbon allotropes and their characteristics are exploited as such or for improving the thermal, electrical, optical, and mechanical properties of other biomaterials. This has now found a broader share in conventional biomaterial space with the generation of nanodiamond, carbon dot, carbon nanoparticles (CNPs), and so forth. With properties of better biocompatibility, intrinsic optical emission, aqueous suspendability, and easier surface conjugation possibilities made CNPs as one of the fore most choice for biological applications especially for use in intracellular spaces. There are various reports available presenting methods of preparing, characterizing, and using CNPs for various biological applications but a collection of information on what makes CNP a suitable biomaterial to achieve those biological activities is yet to be provided in a significant way. Herein, a series of correlations among synthesis, characterization, and mode of utilization of CNP have been incorporated along with the variations in its use as agent for sensing, imaging, and therapy of different diseases or conditions. It is ensembled that how simplified and optimized methods of synthesis is correlated with specific characteristics of CNPs which were found to be suitable in the specific biological applications. These comparisons and correlations among various CNPs, will surely provide a platform to generate new edition of this nanomaterial with improvised applications and newer methods of evaluating structural, physical, and functional properties. This may ensure the eventual use of CNPs for human being for specific need in near future. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Effective outcome from dynamic live-cell-imaging requires utilization of a probe with high emission intensity and low photobleaching. It would be preferable to achieve such properties at a low power of the applied laser to avoid any probable damage to biological cells or tissue. Most of the used small-molecule fluorophores have been reported to show significant photobleaching in a time-dependent manner and require high laser power to gain significant intensity for bioimaging. Carbon nanoparticles have recently been successfully used for cell imaging with low bleaching characteristics but require high laser power and lack optical nonlinearity at low power levels. Here, we report the preparation, characterization, and application of a Nanoscale Carbon (NC) which, on being surface decorated with crescent-shaped poly-lysine (PLNC), provides two-photon fluorescence (TPF) and low bleaching properties. PLNC was found to stain the cytoplasm of C2C12 muscle cells in the first four-hours of incubation with high TPF in the infrared range and can be useful for deep tissue imaging with further improvements.