Hitesh Handa

University of Georgia | UGA · Chemical, Materials and Biomedical Engineering

Nitric oxide (NO) is known to be a potent inhibitor of platelet activation and adhesion. Healthy endothelial cells that line the inner walls of all blood vessels exhibit a NO flux of 0.5-4 × 10(-10) mol cm(-2) min(-1) that helps prevent thrombosis. Materials with a NO flux that is equivalent to this level are expected to exhibit similar anti-thromb...

Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion and activation that can be released from a NO donor species, such as diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) within a polymer coating. In this study, various Food and Drug Administration approved poly(lactic-co-glycolic acid) (PLGA) species w...

The paper describes immobilization methods of bacteriophage P22 and tailspike gp9 proteins isolated from P22 on atomic force microscope (AFM) probes. The paper also reports single molecule force spectroscopy (SMFS) using AFM of the immobilized P22 (or gp9) interactions with substrate-supported O-antigenic lipopolysaccharides (LPS) bilayers. LPS cov...

Biofilm formation on biomaterial interfaces and the development of antibiotic-resistant bacteria have decreased the effectiveness of traditional antibiotic treatment of infections. In this project, ampicillin, a commonly used antibiotic, was conjugated with S-nitroso-N-acetylpenicillamine (SNAP), an S-nitrosothiol compound (RSNO) used for controlle...

Light-controlled therapies offer a promising strategy to prevent and suppress infections caused by numerous bacterial pathogens. Excitation of exogenously supplied photosensitizers (PS) at specific wavelengths elicits levels of reactive oxygen intermediates toxic to bacteria. Porphyrin-based supramolecular nanostructure frameworks (SNF) are effecti...

Hybrid organic-inorganic materials are attracting enormous interest in materials science due to the combination of multiple advantageous properties of both organic and inorganic components. Taking advantage of a simple, scalable, solvent-free hard-sacrificial method, we report the successful fabrication of three-dimensional hybrid porous foams by i...

Graphene oxide (GO) nanosheets are a promising class of carbon‐based materials suitable for application in the construction of medical devices. These materials have inherent antimicrobial properties based on sheet size, but these effects must be carefully traded off to maintain biocompatibility. Chemical modification of functional groups to the lat...

Numerous biomaterials have been developed for application in blood‐contacting medical devices to prevent thrombosis; however, few materials have been applied to full‐scale devices and evaluated for hemocompatibility under clinical blood flow conditions. We applied a dual‐action slippery liquid‐infused (LI) nitric oxide (NO)‐releasing material modif...

Hypothesis: Alginate is widely used in biomedical applications due to its structural and mechanical similarities to human tissue and high biocompatibility. Further, simple ionic crosslinking of alginate allows for the formation of alginate beads capable of drug delivery. S-nitrosoglutathione is a water-soluble molecule that releases nitric oxide in...

Clinical applications of scaffolds and implants have been associated with bacterial infection resulting in impaired tissue regeneration. Nanofibers provide a versatile structure for both antimicrobial molecule delivery and tissue engineering. In this study, the nitric oxide (NO) donor molecule S-nitrosoglutathione (GSNO) and the natural biodegradab...

When blood first encounters the artificial surface of a medical device, a complex series of biochemical reactions is triggered, potentially resulting in clinical complications such as embolism or occlusion, inflammation, or device failure. Preventing thrombus formation on the surface of blood-contacting devices is crucial for maintaining device fun...

Demineralization and breakdown of tooth enamel are characterized by a condition called dental caries or tooth decay, which is caused by two main factors: (1) highly acidic food intake without proper oral hygiene and (2) overactive oral bacteria generating acidic metabolic byproducts. Fluoride treatments have been shown to help rebuild the hydroxyap...

Bacterial contamination of biomaterials is a common problem and a serious threat to human health worldwide. Therefore, the development of multifunctional biomaterials that possess antibacterial properties and can resist infection is a continual goal for biomedical applications. Silk fibroin (SF), approved by the United States Food and Drug Administ...

In this work, a novel coating material based on silk fibroin (SF) and cellulose nanocrystals (CNCs) was developed on biodegradable AZ31 Mg alloy and assessed for corrosion resistance and biocompatibility. Before the application of the coating, AZ31 substrate was modified with a layer of polydopamine to enhance the adhesion of the protective coating...

The chemical composition of particulate matter (PM) in biomass-burning smoke evolves upon aging in the atmosphere. The effect of this evolution on the toxicity of biomass-burning PM is understudied. Here, we burned oak foliage, pine needles, and hickory twigs in an environmental chamber. We used UV radiation to initiate photochemical aging of the e...

Addressing thrombosis and biofouling of indwelling medical devices within healthcare institutions is an ongoing problem. In this work, two types of ultra-low fouling surfaces (i.e., superhydrophobic and lubricant-infused slippery surfaces) were fabricated to enhance the biocompatibility of commercial medical grade silicone rubber (SR) tubes that ar...

Indwelling medical devices currently used to diagnose, monitor, and treat patients invariably suffer from two common clinical complications: broad-spectrum infections and device-induced thrombosis. Currently, infections are managed through antibiotic or antifungal treatment, but the emergence of antibiotic resistance, the formation of recalcitrant...

The clinical application of magnesium (Mg)-based alloys as temporary orthopedic implants is highly limited by their rapid corrosion rate in the physiological environment. Herein, an anti-corrosive polymeric coating based on polycaprolactone (PCL) and lawsone was prepared on AZ31 Mg alloy to improve its corrosion resistance. Lawsone was incorporated...

Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating vascular physiology. The generation of NO from the upregulation of endogenous nitric oxide synthases serves as an efficacious method for inhibiting viral replication in host defense and...

Surface-induced thrombosis is a frequent, critical issue for blood-contacting medical devices that poses a serious threat to patient safety and device functionality. Antithrombotic material design strategies including the immobilization of anticoagulants, alterations in surface chemistries and morphology, and the release of antithrombotic compounds...

Coagulopathic complications during extracorporeal life support (ECLS) result from two parallel processes: 1) foreign surface contact and shear stress during blood circulation and 2) administration of anticoagulant drugs to prevent circuit thrombosis. To address these problems, biocompatible surfaces are developed to prevent foreign surface-induced...

Halloysite nanotubes (HNTs) are natural aluminosilicate clay that have been extensively explored for delivery of bioactive agents in biomedical applications because of their desirable features including unique hollow tubular structure, good biocompatibility, high mechanical strength, and extensive functionality. For the first time, in this work, fu...

Bacterial infections have been increasingly recognized as the major reason for the failure of tissue engineering scaffolds. Therefore, there is a need for novel and multifunctional biomaterials that not only enhance tissue regeneration but also can combat infections. An antibacterial and bioactive scaffold was fabricated in this study by incorporat...

The development of innovative antimicrobial materials is crucial in thwarting infectious diseases caused by microbes, as drug-resistant pathogens are increasing in both number and capacity to detoxify the antimicrobial drugs used today. An ideal antimicrobial material should inhibit a wide variety of bacteria in a short period of time, be less or n...

In this study, the preparation and characterization of nitric oxide (NO) releasing silk fibroin nanoparticles (SF NPs) are described for the first time. S-Nitroso-N-acetylpenicillamine (SNAP)-loaded SF NPs (SNAP-SF NPs) were prepared via an antisolvent/self-assembling method by adding a SNAP/ethanol solution to an aqueous SF solution and freeze-tha...

Blended and coaxial fibers comprising polycaprolactone and gelatin, containing the endogenous nitric oxide (NO) donor S-nitrosoglutathione (GSNO), were electrospun. Both types of fibers had their NO release profiles tested under physiological conditions to examine their potential applications as biomedical scaffolds. The coaxial fibers exhibited a...

Biofilm and thrombus formation on surfaces results in significant morbidity and mortality worldwide, which highlights the importance of the development of efficacious fouling-prevention approaches. In this work, novel highly robust and superhydrophobic coatings with outstanding multiliquid repellency, bactericidal performance, and extremely low bac...

Biomedical surface-associated infections and thrombus formation are two major clinical issues that challenge patient safety and patient the fate of a medical device in the body . Single platform multifunctional surfaces are critical to address both these indwelling medical device-related problems. In this work, bio-inspired approaches are employed...

The novel use of nanofibers as a physical barrier between blood and medical devices has allowed for modifiable, innovative surface coatings on devices ordinarily plagued by thrombosis, delayed healing, and chronic infection. In this study, the nitric oxide (NO) donor S‐nitrosoglutathione (GSNO) is blended with the biodegradable polymers polyhydroxy...

Hypothesis Broad-spectrum antimicrobials are needed to mitigate the complicated nature of antibiotic-resistant infections. It is imperative to formulate new antimicrobials by combining agents with different mechanisms and broader microbial targets. A combined antimicrobial solution could be a highly critical step towards developing a strategy to pr...

Light-absorbing organic particulate matter (PM), or brown carbon (BrC), may constitute an important fraction of combustion PM. Here, we investigate the effect of combustion conditions on the molecular sizes of BrC, their light-absorption properties, and their cytotoxicity. We used toluene in a combustion reactor with highly controlled conditions to...

Microfluidic artificial lungs (µALs) have the potential to improve the treatment and quality of life for patients with acute or chronic lung injury. In order to realize the full potential of this technology (including as a destination therapy), the biocompatibility of these devices needs to be improved to produce long-lasting devices that are safe...

The chances of ventilator‐associated pneumonia (VAP) increases 6‐ to 20‐fold when an endotracheal tube is placed in a patient. VAP is one of the most common hospital‐acquired infections and comprises 86% of the nosocomial pneumonia cases. This work introduces the idea of nitric oxide‐releasing endotracheal tubes (NORel‐ETTs) fabricated by the incor...

Hydrogen sulfide (H2S) is an endogenous gasotransmitter in the human body involved with various physiological functions including cyto-protection, maintaining homeostasis, regulation of organ development, etc. Currently, the use of H2S donors in medical device applications is mostly unexplored. One major challenge is the steady release of the gasot...

A new generation of extracorporeal artificial organ support technologies collectively known as extracorporeal life support (ECLS) devices are being developed for diverse applications to include acute support for trauma-induced organ failure, transitional support for bridge to organ transplant and terminal support for chronic diseases. Across applic...

The development of non-fouling and antimicrobial materials have shown great promise for reducing thrombosis and infection associated with medical devices with aims of improving device safety and decreasing the frequency of antibiotic administration. Here, the design of an antimicrobial, anti-inflammatory and antithrombotic vascular catheter is asse...

Radiotherapy remains a major treatment modality for cancer types such as non-small cell lung carcinoma or NSCLC. To enhance treatment efficacy at a given radiation dose, radiosensitizers are often used during radiotherapy. Herein we report a nanoparticle agent that can selectively sensitize cancer cells to radiotherapy. Specifically, we nitrosylate...

Modern crisis in implantable or indwelling blood-contacting medical devices are mainly due to the dual problems of infection and thrombogenicity. There is a paucity of biomaterials that can address both the problems simultaneously through a singular platform. Taking cues from the body’s own defense mechanism against infection and blood clotting (th...

Coagulation management is the leading challenge during extracorporeal life support (ECLS) due to shear stress and foreign-surface-induced coagulation disturbance during circulation. A nonadhesive, liquid-infused coating called tethered liquid perfluorocarbon (TLP) was developed to prevent adhesion of blood on medical materials. We investigated the...

Biological processes such as infection, angiogenesis, and fibroblast proliferation and migration need to be regulated for effective healing of a wound. Failing to do so, can delay the overall wound healing and add to the suffering and healthcare cost. Endogenous nitric oxide (NO) is a well-known gasotransmitter in the natural healing process in hum...

In medical device design, there is a vital need for a coating that promotes treatment of the patient and simultaneously prevents fouling by biomacromolecules which in turn can progress to infections, thrombosis, and other device-related complications. In this work, hydrophobin SC3 (SC3), a self-assembling amphiphilic protein, was coated on a nitric...

Devices used for extracorporeal circulation are met with two major medical concerns: thrombosis and infection. A device that allows for anticoagulant-free circulation while reducing risk of infection has yet to be developed. We report the use of a copper nanoparticle (Cu NP) catalyst for the release of nitric oxide (NO) from the endogenous donor S-...

Open bone fractures are not only difficult to heal but also are at a high risk of infections. Annual cases of fractures which result from osteoporosis amount to approximately 9 million. Endogenously released nitric oxide (NO) has been shown to play a role in osteogenic differentiation in addition to eradicating infection against a wide variety of p...

Urinary catheterization is one of the most common medical procedures that makes a patient susceptible to infection due to biofilm formation on the urinary catheter. Catheter-associated urinary tract infections (CAUTIs) are responsible for over 1 million cases in the United States alone and cost the healthcare industry more than $350 million every y...

The development of infection resistant materials is of substantial importance as seen with an increase in antibiotic resistance. In this project, the nitric oxide (NO)‐releasing polymer has an added topcoat of zinc oxide nanoparticle (ZnO‐NP) to improve NO‐release and match the endogenous NO flux (0.5 – 4 x 10‐10 mol cm‐2 min‐1). The ZnO‐NP is inco...

Two major challenges faced by medical devices are thrombus formation and infection. In this work, surface tethered nitric oxide (NO) releasing molecules have been presented as a solution to combat infection and thrombosis with a robust release capacity of ca. 1 month while simultaneously improving the non-fouling nature of the material by preventin...

Ever since the role of endogenous nitric oxide (NO) in controlling a wide variety of biological functions was discovered approximately three decades back, multiple NO releasing polymeric materials have been developed. However, most of these materials are typically short lived due to the inefficient incorporation of the NO donor molecules within the...

The explosive growth and implementation of new invasive biomedical devices (>8000 medical devices enter the U.S. market per annum) requires serious consideration of antimicrobial attributes and biocompatibility issues associated with them. The quest for novel therapies for preventing bacterial infections is of uttermost importance in biomedical res...

Diatomaceous earth (DE), a nanoporous silica material comprised of fossilized unicellular marine algae, possesses unique mechanical, molecular transport, optical, and photonic properties exploited across an array of biomedical applications. The utility of DE in these applications stands to be enhanced through the incorporation of nitric oxide (NO)...

The interaction of blood proteins with an implant surface is not only a fundamental phenomenon but is also key to several important medical complications. Plasma proteins binding on the surface of intravascular catheters can promote bacterial adhesion leading to the risk of local and systemic complications such as catheter-related blood infections...

Recent reports on liquid-infused materials have shown promise in creating ultra-low fouling surfaces, but are limited in their ability to prevent bacterial proliferation and prevent platelet activation in blood-contacting applications. In this work, a liquid-infused nitric oxide-releasing (LINORel) material is created by incorporating the nitric ox...

In this study, a two-pronged approach for an antimicrobial coating was employed by crosslinking a superhydrophilic polyzwitterionic topcoat with a nitric oxide (NO) releasing polymer. The polyzwitterion (BPMPC), a terpolymer of 2-methacryloyloxyethyl phosphorylcholine (MPC), n-butyl methacrylate and 4-vinyl benzophenone, exhibits antifouling proper...

Statement of significance: A significant increase in the biomedical device related infections (BDRIs), inability of the currently existing antimicrobial strategies to combat them and a proportional rise in the associated morbidity demands development of novel antimicrobial surfaces. Some of the major challenges associated with the currently used t...

The quest for novel therapies to prevent bacterial infections and blood clots (thrombosis) is of utmost importance in biomedical research due to exponential growth in cases of thrombosis, blood infections, and the emergence of multi-drug resistant strains of bacteria. Endogenous nitric oxide (NO) is a cellular signaling molecule that plays a pivota...

Surface fouling is one of the leading causes of infection associated with implants, stents, catheters, and other medical devices. The surface chemistry of medical device coatings is important in controlling and/or preventing fouling. In this study, we have shown that a combination of nitric oxide releasing hydrophobic polymer with a hydrophilic pol...

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microflu...

In this research article, a computational imaging analysis method is presented for the evaluation of aggregation and anisotropy in both native (unglycated) and glycated fibrin matrix structures. The imaging analysis was used to test the hypothesis that glycated fibrin structures are more aggregated and anisotropic than unglycated (native) fibrin st...