Papers by Jayakumar Rangasamy
Journal of Functional Biomaterials, Aug 2, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Molecular Liquids, Jul 1, 2023
ACS applied bio materials, Dec 13, 2018
International Journal of Nanomedicine, Sep 1, 2017
Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene o... more Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry. Increased uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of free DOCT in Swiss albino mice, indicating the possibility of improved therapeutic effect in the disease model. Qualitative in vivo imaging showed early and enhanced tumor targeted accumulation of CET MAb-DOCT-γ-PGA Nps in EGFR +ve MKN-28-based gastric cancer xenograft, which exhibited efficient arrest of tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted CET MAb-DOCT-γ-PGA Nps could be developed as a substitute to conventional nonspecific chemotherapy, and hence could become a feasible strategy for cancer therapy for EGFR-overexpressing gastric tumors.
International Journal of Biological Macromolecules, Oct 1, 2021
Hydrogels are excellent wound healing materials. However, due to the wear and tear at the wound s... more Hydrogels are excellent wound healing materials. However, due to the wear and tear at the wound site, the hydrogels can lose their structural and functional integrity. To overcome this and to effectively seal the wound and control infection, an in-situ silver nanoparticles (AgNps) incorporated N, O-carboxymethyl chitosan (N, O-CMC) based self-healing hydrogel using ethylenediaminetetraacetic acid-ferric ion (EDTA: Fe3+) complex was developed. The prepared N, O-CMC/AgNps hydrogel was characterized using FTIR, SEM, and TEM. The developed N, O-CMC/AgNps hydrogel was found to be adhesive, injectable, conductive, bio-compatible, and showed antibacterial activity against ATCC and clinical strains of E. coli, K. pneumonia, P. aeruginosa, S. aureus and MRSA. N, O-CMC/AgNps hydrogel also showed anti-biofilm activity against S. aureus, E. coli, and P. aeruginosa (ATCC strains). This developed antibacterial and self-healing N, O-CMC/AgNps hydrogel can be used in the treatment of infected wounds.
Carbohydrate Polymers, Apr 1, 2021
Chitosan (Cs) as a hemostatic agent has been in use to control hemorrage. Composite hydrogel form... more Chitosan (Cs) as a hemostatic agent has been in use to control hemorrage. Composite hydrogel formed by entrapment of vasoconstrictor-potassium aluminium sulfate (0.25 %PA) and coagulation activator-calcium chloride (0.25 %Ca) into Cs (2 %) hydrogel would enhance the hemostatic property of Cs. In this work, the prepared composite hydrogel was injectable, shear thinning, cyto and hemocompatible. The 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel caused rapid blood clotting by accelerating RBC/platelet aggregation and activation of the coagulation cascade. Further, in vivo studies on rat liver and femoral artery hemorrage model showed the efficiency of 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel to achieve hemostasis in a shorter time (20 ± 10 s, 105 ± 31 s) than commercial hemostatic agents-Fibrin sealant (77 ± 26 s, 204 ± 58 s) and Floseal (76 ± 15 s, 218 ± 46 s). In in vivo toxicological study, composite hydrogel showed material retention even after 8 weeks post-surgery, therefore excess hydrogel should be irrigated from site of application. This prepared composite hydrogel based hemostatic agent has potential application in low pressure bleeding sites.
ACS applied bio materials, Dec 21, 2018
Polymicrobial wound infections often requires high dosage of antibiotics and fungicides. However,... more Polymicrobial wound infections often requires high dosage of antibiotics and fungicides. However, prolonged antimicrobial therapies are associated with potential systemic side effects and increased risk for the development of drug resistant microbes. With this focus, we aimed at developing chitosan bandages loaded with anti-microbial (ciprofloxacin and fluconazole) drug loaded nanoparticles for a sustained slow release of drugs. The particle sizes of the prepared ciprofloxacin and flucanazole loaded fibrin nanoparticles were observed to be 132 ± 16 and 175 ± 17 nm respectively. The chitosan bandages with drug containing nanoparticles were flexible with adequate tensile strength and porosity of 80-85%, which would favour excess exudates absorption in an infectious wound. The in vitro toxicity of the bandages studied against human dermal fibroblast (HDF) cell line proved its cytocompatibility. Ciprofloxacin and fluconazole from bandages released upto 14 days in a sustained manner. The antimicrobial drugs loaded bandages showed significant antimicrobial activity towards polymicrobial cultures of C. albicans, E. coli & S. aureus in vitro and ex vivo. In vivo studies were conducted on polymicrobial infected rat wound model. A significant reduction in microbial load was obtained upon application of antimicrobial drug loaded chitosan bandages in vivo.
International Journal of Biological Macromolecules, May 1, 2019
Effective bleeding control is a major concern in trauma and major surgeries. Chitosan (Ch) as hem... more Effective bleeding control is a major concern in trauma and major surgeries. Chitosan (Ch) as hemostatic agent has been widely used and when applied at the site of injury it acts by aggregating blood cells and forming a plug. Our prime interest is to enhance the blood clotting potential of Ch hydrogel. Incorporation of nano bioglass (nBG) with silica (activate coagulation factor XII), calcium (activate intrinsic pathway) and phosphate (initiates extrinsic pathway) ions into Ch hydrogel (protonated amine group) would act simultaneously on mechanisms involved in hemostasis and bring about effective bleeding control. Sol-gel method was followed to synthesize nBG particles and its particle size was found to be 14 ± 3 nm. 2%Ch-5%nBG composite hydrogel was then prepared and characterized using SEM and FTIR. Rheological studies showed the shear-thinning property of the developed hydrogel. 2%Ch-5%nBG hydrogel was observed to be cytocompatible with HUVEC cells. In the in vitro and in vivo (liver and femoral artery injury in rat model) blood clotting analysis, 2%Ch-5%nBG hydrogel formed rapid blood clot compared to control 2%Ch hydrogel. Therefore, the synthesized 2%Ch-5%nBG hydrogel may have great potential to achieve effective bleeding control during critical situations.
Advanced Healthcare Materials, Nov 24, 2017
Bone tissue is one of the most extensive and ubiquitous organs in the human body, and failure of ... more Bone tissue is one of the most extensive and ubiquitous organs in the human body, and failure of its function is one of the main causes of reduced quality of life. [1] The solution presented by organ transplantation involves profound socioeconomic challenges, mainly concerning the lack of tissue donors, multi ple invasive surgeries with extra invasions, and high costs. Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed.
Current Pharmaceutical Design, 2017
Colloid and Interface Science Communications, Nov 1, 2020
Antibiotic loaded calcium sulfate (CS) beads are widely reported to be used as bone void fillers.... more Antibiotic loaded calcium sulfate (CS) beads are widely reported to be used as bone void fillers. Application of these beads has been found effective in the inhibition of bacterial infections and enhanced bone regeneration, though lacking the ability to enhance angiogenesis. Thus, realizing the importance of angiogenesis for complete bone regeneration, magnesium oxide nanoparticles (MgO Nps) of ≤50 nm and tigecycline (Tg) incorporated CS based nanocomposite (Tg-NC) (Tigecycline-Nanocomposite) beads were prepared. N, O-carboxymethyl chitosan solution was chosen as a binder in the preparation of CS-based beads for the enhanced stability. The prepared Tg-NC beads were characterized using SEM, EDS and FTIR. The Tg-NC beads were cytocompatible showing proangiogenic property. The sustained drug release for 10 days from Tg-NC beads was found to be very effective in the inhibition of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Also, Tg-NC beads effectively inhibited biofilms exhibited by Staphylococcus aureus. Thus prepared Tg-NC beads can be used as bone void fillers for inhibiting infections and promoting angiogenesis.
Colloids and Surfaces B: Biointerfaces, May 1, 2019
Highlights PDA nanoparticle was prepared by oxidative self polymerization of dopamine monomers ... more Highlights PDA nanoparticle was prepared by oxidative self polymerization of dopamine monomers Thiol-functionalized HA was prepared by EDC-NHS crosslinking chemistry Composite hydrogel was developed via bioorthogonal Michael-type addition reaction Developed hydrogel was biocompatible and showed sustained drug release profile HUVECs showed enhanced cell migration and capillary tube formation in vitro.
ACS applied bio materials, Jan 4, 2019
Uncontrolled bleeding can lead to many complications that might cause multi organ failures and ev... more Uncontrolled bleeding can lead to many complications that might cause multi organ failures and even death. Of all the hemostatic agents used, chitosan has been reported to show better hemostatic potential. It acts through one mechanism involved in hemostasis that is plug formation by adhering to the injured site. Hence our focus is to enhance the hemostatic potential of chitosan (Ch) hydrogel by incorporating nano whitlockite (nWH: Ca 18 Mg 2 (HPO 4) 2 (PO 4) 12) that would release Ca 2+ , Mg 2+ and PO 4 3ions which would simultaneously initiate the coagulation cascade. Ch-nWH composite hydrogel can act simultaneously on different mechanisms involved in hemostasis and bring about rapid bleeding control. The nWH particles were synthesized using precipitation technique and were characterized. Particle size of nWH was found to be 75 ± 5 nm. Composite hydrogel was characterized using FTIR and XRD to confirm the presence of different constituents of the hydrogel. Rheological studies showed the shear-thinning property and increased elastic modulus of the composite hydrogel compared to Ch hydrogel. 2%Ch-4%nWH hydrogel was observed to be cytocompatible with Human Umbilical Vein Endothelial Cells (HUVEC). In the in vitro blood clotting analysis using citrated human whole blood, 2%Ch-4%nWH hydrogel showed rapid blood clot formation compared to control 2%Ch hydrogel. Further in vivo experiments performed on liver and femoral artery injuries created on Sprague Dawley (S.D) rat model reveals that 2%Ch-4%nWH hydrogel promoted rapid bleeding control and less volume of blood loss compared to Ch hydrogel. These in vitro and in vivo results showed that incorporation of nWH has enhanced the hemostatic potential of Ch hydrogel. Therefore, the synthesized 2%Ch-4%nWH hydrogel may be a promising system that could bring about rapid hemostasis during life threatening bleeding.
Biomaterials Research, Jun 1, 2023
Sensing the mechanical properties of the substrates or the matrix by the cells and the tissues, t... more Sensing the mechanical properties of the substrates or the matrix by the cells and the tissues, the subsequent downstream responses at the cellular, nuclear and epigenetic levels and the outcomes are beginning to get unraveled more recently. There have been various instances where researchers have established the underlying connection between the cellular mechanosignalling pathways and cellular physiology, cellular differentiation, and also tissue pathology. It has been now accepted that mechanosignalling, alone or in combination with classical pathways, could play a significant role in fate determination, development, and organization of cells and tissues. Furthermore, as mechanobiology is gaining traction, so do the various techniques to ponder and gain insights into the still unraveled pathways. This review would briefly discuss some of the interesting works wherein it has been shown that specific alteration of the mechanical properties of the substrates would lead to fate determination of stem cells into various differentiated cells such as osteoblasts, adipocytes, tenocytes, cardiomyocytes, and neurons, and how these properties are being utilized for the development of organoids. This review would also cover various techniques that have been developed and employed to explore the effects of mechanosignalling, including imaging of mechanosensing proteins, atomic force microscopy (AFM), quartz crystal microbalance with dissipation measurements (QCMD), traction force microscopy (TFM), microdevice arrays, Spatio-temporal image analysis, optical tweezer force measurements, mechanoscanning ion conductance microscopy (mSICM), acoustofluidic interferometric device (AID) and so forth. This review would provide insights to the researchers who work on exploiting various mechanical properties of substrates to control the cellular and tissue functions for tissue engineering and regenerative applications, and also will shed light on the advancements of various techniques that could be utilized to unravel the unknown in the field of cellular mechanobiology.
Advances in Polymer Science, 2021
Recent years have seen tremendous interest among researchers in the field of biosensors for the a... more Recent years have seen tremendous interest among researchers in the field of biosensors for the application of medical and agricultural products, processed food, and environmental monitoring. To prepare a stable and reliable biosensor, immobilization of biological responses elements (BRE) plays a critical role. Chitosan, a natural polysaccharide with non-toxic and gellable properties, and the presence of functional groups would act as a suitable substrate material. The presence of functional groups would provide cross-linking moieties increasing the mechanical stability, immobilization of BRE and nanomaterials. Additionally, a chitosan composite/nanocomposite-based biosensor would provide enhanced conductivity and sensitivity of detecting various biological analytes such as glucose, H2O2, antigens, DNA, and biomolecules. This review provides a comprehensive understanding of various strategies of utilizing chitosan as a substrate for various biosensing applications.
Advanced Healthcare Materials, Dec 1, 2017
Current Medicinal Chemistry, Oct 25, 2017
Materials Science and Engineering: C, Aug 1, 2021
Tendon being a hypocellular, low vascularized tissue often requires assistance for restoration af... more Tendon being a hypocellular, low vascularized tissue often requires assistance for restoration after complete tear. Tendon tissue engineering aims in the development of suitable scaffold that could support the regeneration of tendon after damage. The success of such scaffolds is dependent on its integration with the native tissue which in turn is influenced by the cell-material interaction. In this work aligned poly(ε-caprolactone)/collagen (PCL/collagen) multiscale fibers were developed and plasma treatment using argon, nitrogen and its combination was accessed for inducing tenogenic differentiation in mesenchymal stem cells. The developed fibers mimicked tendon extracellular matrix (ECM) which upon plasma treatment maintained moderate hydrophilicity. Oxygen and nitrogen containing groups were observed to be incorporated after argon and nitrogen treatment respectively. Statistically significant (p < 0.001) enhancement was observed in average and root mean square (RMS) roughness after plasma treatment with the maximum in argon treated fibers. Vitronectin was competitively (statistically significant, p < 0.05) adsorbed after argon and combination treatment whereas nitrogen treatment led to the competitive adsorption of fibronectin (statistically significant, p < 0.05). Human mesenchymal stem cells (hMSCs) showed enhanced proliferation and attachment on plasma treated fibers. Increased porosity due to the presence of sacrificial collagen nanofibers improved cell infiltration which was further enhanced upon plasma treatment. RhoA activation was observed (statistically significant, p < 0.05) on aligned PCL/collagen multiscale fibers and PCL microfibers, which proved its impact on tenogenic differentiation. Further enhancement in rhoA expression was observed on argon (p < 0.01) and combination plasma (p < 0.05) treated fibers. Tenogenic differentiation of hMSCs was enhanced (statistically significant) on argon plasma treated aligned fibers which was confirmed by the expression of scleraxis, mohawk (early markers) and tenomodulin (late marker) at protein level and mohawk, collagen I, collagen III (early markers), thrombospondin 4 and tenascin C (late markers) at gene level. Thus argon plasma treatment on aligned fibers is an effective method to induce tenogenesis even in non-tenogenic media.
Tissue Engineering and Regenerative Medicine, Jan 17, 2020
BACKGROUND: Human adipose tissue is a great source of translatable biomaterials owing to its ease... more BACKGROUND: Human adipose tissue is a great source of translatable biomaterials owing to its ease of availability and simple processing. Reusing discardable adipose tissue for tissue regeneration helps in mimicking the exact native microenvironment of tissue. Over the past 10 years, extraction, processing, tuning and fabrication of adipose tissue have grabbed the attention owing to their native therapeutic and regenerative potential. The present work gives the overview of next generation biomaterials derived from human adipose tissue and their development with clinical relevance. METHODS: Around 300 articles have been reviewed to widen the knowledge on the isolation, characterization techniques and medical applications of human adipose tissue and its derivatives from bench to bedside. The prospective applications of adipose tissue derivatives like autologous fat graft, stromal vascular fraction, stem cells, preadipocyte, adipokines and extracellular matrix, their behavioural mechanism, rational property of providing native bioenvironment, circumventing their translational abilities, recent advances in featuring them clinically have been reviewed extensively to reveal the dormant side of human adipose tissue. RESULTS: Basic understanding about the molecular and structural aspect of human adipose tissue is necessary to employ it constructively. This review has nailed the productive usage of human adipose tissue, in a stepwise manner from exploring the methods of extracting derivatives, concerns during processing and its formulations to turning them into functional biomaterials. Their performance as functional biomaterials for skin regeneration, wound healing, soft tissue defects, stem cell and other regenerative therapies under in vitro and in vivo conditions emphasizes the translational efficiency of adipose tissue derivatives. CONCLUSION: In the recent years, research interest has inclination towards constructive tissue engineering and regenerative therapies. Unravelling the maximum utilization of human adipose tissue derivatives paves a way for improving existing tissue regeneration and cellular based therapies and other biomedical applications.
ACS Applied Materials & Interfaces, Sep 12, 2011
In this work, we developed biodegradable chitin nanogels (CNGs) by controlled regeneration method... more In this work, we developed biodegradable chitin nanogels (CNGs) by controlled regeneration method. For multifunctionalization, we have conjugated CNGs with MPA-capped-CdTe-QDs (QD-CNGs) for the in vitro cellular localization studies. In addition, the Bovine Serum Albumin (BSA) was loaded on to QD-CNGs (BSA-QD-CNGs). The CNGs, QD-CNGs, and BSA-QD-CNGs were well-characterized by SEM and AFM, which shows that the nanogels are in the range of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;100 nm. These were further characterized by FT-IR and Cyclic Voltametry. The cytocompatibility assay showed that the nanogels are nontoxic to L929, NIH-3T3, KB, MCF-7, PC3, and VERO cells. The cell uptake studies of the QD-CNGs were analyzed, which showed retention of these nanogels inside the cells (L929, PC3, and VERO). In addition, the protein loading efficiency of the nano gels has also been analyzed. Our preliminary studies reveal that these multifunctionalized nanogels could be useful for drug delivery with simultaneous imaging and biosensing.
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Papers by Jayakumar Rangasamy