Understanding thermodynamics and kinetics of PEDOT:PSS using ATR-FTIR and density functional theory

Authors: Devyesh Rana, John Biswakarma, Steven R. Lustig

Abstract: This work demonstrates poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) and divinyl sulfone (DVS) cross-linking to form insoluble and porous PEDOT:PSS-DVS hydrogels. We propose a reaction mechanism and demonstrate the kinetics of a PEDOT:PSS modification that prevents PEDOT:PSS dispersibility. PSS and DVS undergo a second-order reaction between the DVS secondary carbocations and PSS oxygen anion to form a PSS-DVS network. The kinetics, from real-time attenuated total reflectance-Fourier transform infrared spectroscopy and density functional theory, reveal a temperature-dependent rate expression with a 1.458 1/s pre-exponential factor and a 2.429 kcal/mol activation energy. Cryogelation, phase separation, and phase inversion methods induce porosity in the PEDOT:PSS-DVS hydrogels with pore sizes ranging from 12 to 121 μm. Most importantly, the porous PEDOT:PSS-DVS hydrogels do not redisperse in solution. The results provide evidence for the reaction mechanism and kinetics of porous nondispersible PEDOT:PSS-DVS hydrogels.

Full Article Link: https://pubs.acs.org/doi/10.1021/acsomega.4c05552

Ph. D. Thesis: Carbon Chemical Speciation and Polymerization in Liquid Metals

Author: Devyesh Rana

Thesis Link: https://www.proquest.com/docview/3049675683

Patent: Continuous reactor and additive manufacturing of metals with nanostructured inclusions

Inventors: Steven Lustig, Randall Erb, Devyesh Rana

Abstract: Provided are methods and flow reactors for the production of covetic materials under continuous flow conditions.

Full Patent Link: https://patents.google.com/patent/US20240024950A1/en

Engineering injectable, biocompatible, and highly elastic bioadhesive cryogels

Authors: Devyesh Rana, Thibault Colombani, Bahram Saleh, Halimatu S. Mohammed, Nasim Annabi, Sidi A. Bencherif

Abstract: The extracellular matrix (ECM), an integral component of all organs, is inherently tissue adhesive and plays a pivotal role in tissue regeneration and remodeling. However, man-made three-dimensional (3D) biomaterials that are designed to mimic ECMs do not intrinsically adhere to moisture-rich environments and often lack an open macroporous architecture required for facilitating cellularization and integration with the host tissue post-implantation. Furthermore, most of these constructs usually entail invasive surgeries and potentially a risk of infection. To address these challenges, we recently engineered biomimetic and macroporous cryogel scaffolds that are syringe injectable while exhibiting unique physical properties, including strong bioadhesive properties to tissues and organs. These biomimetic catechol-containing cryogels were prepared from naturally-derived polymers such as gelatin and hyaluronic acid and were functionalized with mussel-inspired dopamine (DOPA) to impart bioadhesive properties. We found that using glutathione as an antioxidant and incorporating DOPA into cryogels via a PEG spacer arm led to the highest tissue adhesion and improved physical properties overall, whereas DOPA-free cryogels were weakly tissue adhesive. As shown by qualitative and quantitative adhesion tests, DOPA-containing cryogels were able to adhere strongly to several animal tissues and organs such as the heart, small intestine, lung, kidney, and skin. Furthermore, these unoxidized (i.e., browning-free) and bioadhesive cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented the ex vivo activation of primary bone marrow-derived dendritic cells. Finally, in vivo data suggested good tissue integration and a minimal host inflammatory response when subcutaneously injected in rats. Collectively, these minimally invasive, browning-free, and strongly bioadhesive mussel-inspired cryogels show great promise for various biomedical applications, potentially in wound healing, tissue engineering, and regenerative medicine.

Full Article Link: https://doi.org/10.1016/j.mtbio.2023.100572

A review of covetics – current understanding and future perspectives

Authors: Devyesh Rana, Kätchen Lachmayr, Steven Raymond Lustig

Abstract: Covetics are a novel class of metal–carbon composites traditionally fabricated in an induction furnace with high power electrical current in the liquid metal–carbon mixture. The electrical current facilitates chemical conversion of carbon feedstock into graphene–metal crystalline structures. We explore the synthesis mechanism and hypothesize that carbon–metal species, rather than purely-carbon ions, are the reactant species driving the covetic reaction. Experimental mechanical and electrical property characterization in aluminum, silver, and copper covetics demonstrates improved tensile, hardness, and conductivity of covetic metals over pure metal controls. The literature proves that significantly improved material properties are possible with homogeneously distributed graphitic carbon in metal. High resolution transmission electron microscopy shows stripe, multidirectional, and alternating carbon–metal plane lattice structure nanocarbon patterns for aluminum, copper, and silver covetics, respectively, as well as high- and low-carbon concentration regions. Covetic Raman spectra and theoretical calculations indicate characteristic graphene signatures and the possibility of aluminum–graphene and silver–graphene bonding. This review consolidates the current literature and provides new avenues for research.

Full Article Link: https://doi.org/10.1039/D2NA00500J

Patent: Engineering a porous conductive pedot:pss-dvs scaffold for microbial fuel cell air cathodes

Inventors: Steven Lustig, Devyesh Rana, Katchen Lachmayr

Patent Abstract: Disclosed are methods of making porous polymeric materials. Also provided herein are porous polymeric materials prepared by the disclosed methods.

Full Patent Filing: https://patents.google.com/patent/US20210324169A1/en

Needle-injectable microcomposite cryogel scaffolds with antimicrobial properties

Authors: Kasturi Joshi Navare, Thibault Colombani, Mahboobeh Rezaeeyazdi, Nicole Bassous, Devyesh Rana, Thomas Webster, Adnan Memic & Sidi A. Bencherif 

Abstract: Porous three-dimensional hydrogel scaffolds have an exquisite ability to promote tissue repair. However, because of their high water content and invasive nature during surgical implantation, hydrogels are at an increased risk of bacterial infection. Recently, we have developed elastic biomimetic cryogels, an advanced type of polymeric hydrogel, that are syringe-deliverable through hypodermic needles. These needle-injectable cryogels have unique properties, including large and interconnected pores, mechanical robustness, and shape-memory. Like hydrogels, cryogels are also susceptible to colonization by microbial pathogens. To that end, our minimally invasive cryogels have been engineered to address this challenge. Specifically, we hybridized the cryogels with calcium peroxide microparticles to controllably produce bactericidal hydrogen peroxide. Our novel microcomposite cryogels exhibit antimicrobial properties and inhibit antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa), the most common cause of biomaterial implant failure in modern medicine. Moreover, the cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented activation of primary bone marrow-derived dendritic cells ex vivo. Finally, in vivo data suggested tissue integration, biodegradation, and minimal host inflammatory responses when the antimicrobial cryogels, even when purposely contaminated with bacteria, were subcutaneously injected in mice. Collectively, these needle-injectable microcomposite cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine.

Full Article Link: https://doi.org/10.1038/s41598-020-75196-1

Patent: Injectable, bioadhesive cryogel scaffolds for biomedical uses

Inventors: Devyesh Rana, Sidi A. Bencherif, Nasim Annabi

Abstract: Disclosed herein are functionalized dopamine derivatives comprising an optionally substituted acrylic acid moiety and optionally a polyethylene glycol linking moiety. The functionalized dopamine derivatives are useful in cryogel formulations to improve the adhesivity of the cryogel, while preventing undesirable oxidation typically associated with dopamine-containing hydrogels and cryogels. Properties such as cryogel adhesivity, pore size, and interconnectivity are tunable features. Also provided herein are methods of treating a wound or promoting tissue regeneration with a cryogel of the invention or a formulation comprising such a cryogel.

Full Patent Link: https://patents.google.com/patent/US11850325B2/en

Effectiveness of common fabrics to block aqueous aerosols of virus-like nanoparticles

Authors: Steven R. Lustig, John Biswakarma, Devyesh Rana, Susan H. Tilford, Weike Hu, Ming Su, Michael S. Rosenblatt

Abstract: Layered systems of commonly available fabric materials can be used by the public and healthcare providers in face masks to reduce the risk of inhaling viruses with protection that is about equivalent to or better than the filtration and adsorption offered by 5-layer N95 respirators. Over 70 different common fabric combinations and masks were evaluated under steady-state, forced convection air flux with pulsed aerosols that simulate forceful respiration. The aerosols contain fluorescent virus-like nanoparticles to track transmission through materials that greatly assist the accuracy of detection, thus avoiding artifacts including pore flooding and the loss of aerosol due to evaporation and droplet breakup. Effective materials comprise both absorbent, hydrophilic layers and barrier, hydrophobic layers. Although the hydrophobic layers can adhere virus-like nanoparticles, they may also repel droplets from adjacent absorbent layers and prevent wicking transport across the fabric system. Effective designs are noted with absorbent layers comprising terry cloth towel, quilting cotton, and flannel. Effective designs are noted with barrier layers comprising nonwoven polypropylene, polyester, and polyaramid.

Full Article Link: https://pubs.acs.org/doi/10.1021/acsnano.0c03972

Strategies to prevent dopamine oxidation and related cytotoxicity using various antioxidants and nitrogenation

Authors: Devyesh Rana, Thibault Colombani, Halimatu S. Mohammed, Loek J. Eggermont, Samantha Johnson, Nasim Annabi, & Sidi A. Bencherif

Abstract: Dopamine (DA) plays several important roles in the brain and body and has recently been used as a bioadhesive precursor for medical applications. However, DA oxidizes immediately when exposed to oxygen and rapidly polymerizes into polydopamine (PDA), leading to oxidative stress, cytotoxicity, and loss of DA functionalities. As a result, preventing rapid oxidation of DA is of paramount importance but still remains a major challenge. Here, we report several strategies to impede DA oxidation in relevant aqueous solutions (i.e., water, PBS, and cell culture media). One strategy is based on using reducing agents or antioxidants such as glutathione in its reduced state (GSH) and sodium tetraborate (commonly known as borax). Another strategy is based on nitrogenation, a method used to preserve DA in its reduced form by creating an oxygen-free environment. Our data suggest that the antioxidant properties of GSH and borax substantially decreased DA oxidation for up to 2 months. Nitrogenation or oxygen removal further prevented DA oxidation, enhancing its shelf life for longer periods of time. When tested with mammalian cells, preventing DA oxidation with GSH dramatically improved viability of 3T3 fibroblasts and T cells. These results demonstrate that the use of antioxidants, alone or in combination with nitrogenation, can help prevent DA oxidation and improve its stability for cell-based studies or for the design and development of biomaterials.

Full Article Link: https://doi.org/10.1007/s42247-019-00037-5

Autoclavable and injectable cryogels for biomedical applications

Authors: Pierre Villard, Mahboobeh Rezaeeyazdi, Thibault Colombani, Kasturi Joshi-Navare, Devyesh Rana, Adnan Memic, and Sidi A. Bencherif

Abstract: Prior to any clinical application, terminal sterilization of biomaterials is a critical process imposed by the Food and Drug Administration. Of all the methods available for sterilization, high-pressure steam sterilization such as autoclaving is the most widely used. While autoclave sterilization minimizes pathogen contamination, it can dramatically impact both structural and biological properties of biomaterials. It has recently been reported that injectable cryogels with shape memory properties hold great promises as 3D macroporous biomimetic scaffolds for biomedical applications including tissue engineering. In this study, the impact of autoclave sterilization on properties of a series of cryogels is measured. Unlike conventional hydrogels, cryogels made of natural polymers demonstrate a strong resilience to autoclave sterilization. This process does not alter either their macrostructural or unique physical properties including syringe injectability. The scaffolds’ bioactive sites are preserved and autoclaved cryogels retain their excellent cytological compatibility post-autoclaving. Furthermore, autoclaved cryogels do not trigger a notable activation of primary murine bone marrow-derived dendritic cells suggesting a minimal risk for biomaterial-induced inflammation, which is further confirmed by an in vivo histologic analysis. In summary, these results further demonstrate the huge potential of cryogels in the biomedical field and their capacity to be translated into clinical applications.

Full Article Link: https://doi.org/10.1002/adhm.201900679

Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels

 

Authors: Ehsan Shirzaei Sani, Ahmad Kheirkhah, Devyesh Rana, Zhongmou Sun, William Foulsham, Amir Sheikhi, Ali Khademhosseini, Reza Dana, Nasim Annabi

Abstract: Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.

Full Article Link: https://doi.org/10.1126/sciadv.aav1281

Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing

Author: Nasim Annabi, Devyesh Rana, Ehsan Shirzaei Sani, Roberto Portillo-Lara, Jessie L. Gifford, Mohammad M. Fares, Suzanne M. Mithieux, Anthony S. Weiss

Abstract: Hydrogel-based bioadhesives have emerged as alternatives for sutureless wound closure, since they can mimic the composition and physicochemical properties of the extracellular matrix. However, they are often associated with poor mechanical properties, low adhesion to native tissues, and lack of antimicrobial properties. Herein, a new sprayable, elastic, and biocompatible composite hydrogel, with broad-spectrum antimicrobial activity, for the treatment of chronic wounds is reported. The composite hydrogels were engineered using two ECM-derived biopolymers, gelatin methacryloyl (GelMA) and methacryloyl-substituted recombinant human tropoelastin (MeTro). MeTro/GelMA composite hydrogel adhesives were formed via visible light-induced crosslinking. Additionally, the antimicrobial peptide Tet213 was conjugated to the hydrogels, instilling antimicrobial activity against Gram (+) and (−) bacteria. The physical properties (e.g. porosity, degradability, swellability, mechanical, and adhesive properties) of the engineered hydrogel could be fine-tuned by varying the ratio of MeTro/GelMA and the final polymer concentration. The hydrogels supported in vitro mammalian cellular growth in both two-dimensional and three dimensional cultures. The subcutaneous implantation of the hydrogels in rats confirmed their biocompatibility and biodegradation in vivo. The engineered MeTro/GelMA-Tet213 hydrogels can be used for sutureless wound closure strategies to prevent infection and promote healing of chronic wounds.

Full Article: https://doi.org/10.1016/j.biomaterials.2017.05.011