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  1. Home
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Browsing by Author "Thankam, FG"

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    Alginate based hybrid copolymer hydrogels-Influence of pore morphology on cell-material interaction
    (CARBOHYDRATE POLYMERS, 2014) Thankam, FG; Muthu, J
    Alginate based hybrid copolymer hydrogels with unidirectional pore morphology were prepared to achieve synergistic biological performance for cardiac tissue engineering applications. Alginate based hybrid copolymer (ALGP) were prepared using alginate and poly(propylene fumarate) (HT-PPF) units. Different hybrid bimodal hydrogels were prepared by covalent crosslinking using poly(ethylene glycol diacrylate) and vinyl monomer viz acrylic acid, methyl methacrylate, butyl methacrylate and N-N'-methylene-bis-acrylamide and ionic crosslinking with calcium. The morphologically modified hydrogels (MM-hydrogels) with unidirectional elongated pores and high aspect ratio were prepared. MM-hydrogels favour better mechanical properties; it also enhances cell viability and infiltration due to unidirectional pores. However, the crosslinkers influence the fibroblast infiltration of these hydrogels. Synthesis of collagen and fibroblast infiltration was greater for alginate copolymer crosslinked with poly(ethylene glycol diacrylate-acrylic acid (ALGP-PA) even after one month (288%). This hybrid MM-hydrogel promoted cardiomyoblast growth on to their interstices signifying its potent applications in cardiac tissue engineering. (C) 2014 Elsevier Ltd. All rights reserved.
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    Alginate-polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering
    (JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2015) Thankam, FG; Muthu, J
    The physiochemical and biological responses of tissue engineering hydrogels are crucial in determining their desired performance. A hybrid comacromer was synthesized by copolymerizing alginate and poly(mannitol fumarate-co-sebacate) (pFMSA). Three bimodal hydrogels pFMSA-AA, pFMSA-MA and pFMSA-NMBA were synthesized by crosslinking with Ca2+ and vinyl monomers acrylic acid (AA), methacrylic acid (MA) and N,N'-methylene bisacrylamide (NMBA), respectively. Though all the hydrogels were cytocompatible and exhibited a normal cell cycle profile, pFMSA-AA exhibited superior physiochemical properties viz non-freezable water content (58.34%) and water absorption per unit mass (0.97 g water/g gel) and pore length (19.92 +/- 3.91 mu m) in comparing with other two hydrogels. The increased non-freezable water content and water absorption of pFMSA-AA hydrogels greatly influenced its biological performance, which was evident from long-term viability assay and cell cycle proliferation. The physiochemical and biological favorability of pFMSA-AA hydrogels signifies its suitability for cardiac tissue engineering. (C) 2015 Elsevier Inc. All rights reserved.
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    Biosynthetic alginate-polyester hydrogels with inherent free radical scavenging activity promote cellular response
    (JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS, 2013) Thankam, FG; Muthu, J
    The prevention of deleterious effects of reactive oxygen species on the cell growth by biosynthetic hydrogels based on alginate-polyester copolymer was studied using H2O2 as the model ROS molecule. Chemically cross-linked biosynthetic hydrogels of alginate-co-poly(propylene fumarate)-n-butyl methacrylate, alginate-co-poly(propylene fumarate)-methyl methacrylate, alginate-co-poly(propylene fumarate)-2-hydroxyethyl methacrylate, and alginate-co-poly(propylene fumarate)-N,N-methylene bisacrylamide with different biostabilities were prepared. We found that they were able to resist reactive oxygen species penetration into the cell to a greater extent which was evident from the live/dead assay, and increased intracellular glutathione levels compared to the H2O2-treated control. The hydrogels maintained the genomic integrity which was confirmed by comet assay. The inherent protective effects of these hydrogels without any antioxidant moiety may be mediated by dual mechanism: (a) prevention of migration of H2O2 into the cells by calcium-induced conformational changes and rigidity in phospholipids present in the surface membrane of cells by the calcium generated from degradation of hydrogel and (b) by the dilution of H2O2 by the free water in the hydrogel. These hydrogels have potential as injectable hydrogels to manage myocardial infarction and ischemia.
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    Biosynthetic hydrogels-Studies on chemical and physical characteristics on long-term cellular response for tissue engineering
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2014) Thankam, FG; Muthu, J
    Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate - poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering. (C) 2013 Wiley Periodicals, Inc.
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    Free radical scavenging injectable hydrogels for regenerative therapy
    (MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, 2017) Komeri, R; Thankam, FG; Muthu, J
    Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free IT electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. (C) 2016 Elsevier B.V. All rights reserved.
  • Item
    Growth and survival of cells in biosynthetic poly vinyl alcohol-alginate IPN hydrogels for cardiac applications
    (COLLOIDS AND SURFACES B-BIOINTERFACES, 2013) Thankam, FG; Muthu, J; Sankar, V; Gopal, RK
    Biosynthetic hydrogels of poly vinyl alcohol-calcium alginate were prepared as semi (semi-IPN hydrogel, PAH) and full interpenetrating polymeric network (IPN hydrogel, PAHG) for tissue engineering of cardiac tissue. The biological response of these hydrogels was studied. The IPN hydrogel exhibits amphiphilic nature and moderate equilibrium water content. The IPN hydrogel inherits the water as structured one along with more free water. The IPN hydrogel has adequate mechanical strength and fatigue life and stability in physiological media over the semi-IPN hydrogel. The structured water along with more free water in IPN hydrogel promotes blood compatibility, cell adhesion and proliferation and maintains three dimensional growths of L929 fibroblast and H9C2 cardiomyoblasts. IPN hydrogel maintain long term cell viability and infiltration with exchange of nutrients in the interstices of the hydrogel. The IPN hydrogel, PAHG is a promising material for engineering cardiac tissue. (C) 2013 Elsevier B.V. All rights reserved.
  • Item
    Infiltration and sustenance of viability of cells by amphiphilic biosynthetic biodegradable hydrogels
    (JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2014) Thankam, FG; Muthu, J
    Amphiphilic biosynthetic hydrogels comprising natural polysaccharide alginate (I) and synthetic polyester polypropylene fumarate (II) units were prepared by crosslinking the copolymer of I and II with calcium ion and vinyl monomers viz, 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), butyl methacrylate (BMA) and N,N'-methylene bisacrylamide (NMBA). Three fast degradable hydrogels, ALPF-MMA, ALPF-HEMA and ALPF-BMA and one slow degradable hydrogel ALPF-NMBA were prepared. These hydrogels are amphiphilic and able to hold sufficient amount of proteins on their surfaces. All these hydrogels are found to be hemocompatible, cytocompatible and genocompatible. ALPF-NMBA promotes infiltration of L929 fibroblasts and 3D growth of H9c2 cardiomyoblasts and long-term viability.
  • Item
    Influence of matrix and bulk behaviour of an injectable hydrogel on the survival of encapsulated cardiac cells
    (RSC ADVANCES, 2015) Komeri, R; Thankam, FG; Muthu, J
    Cytocompatibility, suitable porosity, higher equilibrium water content and tissue like elasticity are the demanding criteria required to design a hydrogel for cell encapsulation and delivery. Here a mechanically stable cell supporting synthetic hydrogel was fabricated from poly(propylene fumarate-co-ethylene glycol)/PEGDA by redox initiating polymerisation for cell encapsulation. A hydrogel prepared with 93.5% poly(propylene fumarate-co-ethylene glycol) and 6.5% PEGDA acquired matrix and bulk characteristics of equilibrium water content (EWC) 84.45 + 0.80%, freezable water content 67.93%, Young modulus 212.2 +/- 0.02 kPa and pore diameter 88.64 +/- 18.96 mu m. This hydrogel with higher free water content, favourable pore dimensions and mechanical strength was used to encapsulate cardiomyoblasts. The encapsulated cardiomyoblasts were showing increasing viability from 3-30 days with viable green fluorescence. The matrix and bulk characteristics of the hydrogel are favourable and elicited uniform, green fluorescing, live cardiomyoblasts (H9c2) inside with 150% cell viability (MTT assay) and uniform ECM protein distribution after 30 days. The slow in vitro degradation of the hydrogel in physiological-like conditions is favourable for the delivery and retention of the encapsulated cells at the injection site.
  • Item
    Influence of physical and mechanical properties of amphiphilic biosynthetic hydrogels on long-term cell viability
    (JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, 2014) Thankam, FG; Muthu, J
    Maintaining the mechanical properties of biofunctional hydrogels of natural resources for tissue engineering and biomedical applications for an intended period of duration is a challenge. Though anionic polysaccharide alginate has been hailed for its excellent biomimetic characters for tissue engineering, it usually fails in load bearing and other dynamic mechanical environment. In this paper this issue was addressed by copolymerizing alginate with the biocompatible and mechanically robust synthetic biodegradable polyester and crosslinking with polyethylene glycol diacrylate (PEGDA) and vinyl comonomers, 2-hydroxy ethyl methacrylate (HEMA), methyl methacrylate (MMA) and N N' methylene bis acrylamide (NMBA) to form three hydrogels. All three hydrogels were amphiphilic, hemocompatible and non-cytotoxic. These hydrogels exhibited appreciable water holding capacity. Comparatively, hydrogel prepared with PEGDA-NMBA crosslinkers displayed larger pore size, increased crosslinking, higher tensile strength and controlled degradation. With appreciable swelling and EWC, this hydrogel elicited better biological responses with long-term cell viability for cardiac tissue engineering. (C) 2014 Elsevier Ltd. All rights reserved.
  • Item
    Influence of plasma protein-hydrogel interaction moderated by absorption of water on long-term cell viability in amphiphilic biosynthetic hydrogels
    (RSC ADVANCES, 2013) Thankam, FG; Muthu, J
    Studies on the effect of plasma protein binding on biosynthetic hydrogels on the long term cell viability and infiltration onto the hydrogel scaffolds were carried out. Three hydrogels, PALG-P (PALG-co-PEGDA), PALG-PA (PALG-co-PEGDA-co-AA) and PALG-PB (PALG-co-PEGDA-co-BMA) were prepared using a copolymer of poly(propylene fumarate)-co-alginate (PALG) and cross-linker PEGDA and vinyl monomers. The nature of vinyl monomer largely influences the nature of water (structured bound water/freezing free water) present in the hydrogel and also the adsorption of protein, cell growth and infiltration. The extensively bound structured water as observed with butyl methacrylate based poly(propylene fumarate)-co-alginate-PEGDA hydrogel (PALG-PB) do not favour absorption of proteins and sustain cell growth and infiltration for long duration. Though moderately bound structured water favours absorption of protein moderately as observed with poly(propylene fumarate)-co-alginate-PEGDA hydrogel (PALG-PB), it does not sustain the cell growth. However, the minimally bound structured water favours absorption of protein extensively as observed with acrylic acid based poly(propylene fumarate)-co-alginate-PEGDA hydrogel (PALG-PA) and sustains the cell growth and infiltration for long duration.
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