Mechanical properties of alginate hydrogels manufactured using external gelation.

Alginate hydrogels are commonly used in biomedical applications such as scaffolds for tissue engineering, drug delivery, and as a medium for cell immobilisation. Multivalent cations are often employed to create physical crosslinks between carboxyl and hydroxyl moieties on neighbouring polysaccharide chains, creating hydrogels with a range of mechanical properties. This work describes the manufacture and characterisation of sodium alginate hydrogels using the divalent cations Mg(2+), Ca(2+) and Sr(2+) to promote gelation via non-covalent crosslinks. Gelation time and Young׳s modulus are characterised as a function of cation and alginate concentrations. The implications of this work towards the use of environmental elasticity to control stem cell differentiation are discussed.

[1]  K W Anderson,et al.  Cell-interactive Alginate Hydrogels for Bone Tissue Engineering , 2001, Journal of dental research.

[2]  I. Colombo,et al.  Mesh size distribution determination of interpenetrating polymer network hydrogels , 2012 .

[3]  L. Chan,et al.  Production of alginate microspheres by internal gelation using an emulsification method. , 2002, International journal of pharmaceutics.

[4]  W. Hennink,et al.  Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing. , 2007, Tissue engineering.

[5]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[6]  Hertz.  On the Contact of Elastic Solids , 1882 .

[7]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical Reviews.

[8]  S. Bryant,et al.  Cell encapsulation in biodegradable hydrogels for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[9]  Y. Marcus.  The standard partial molar volumes of ions in solution. Part 4. Ionic volumes in water at 0-100 degrees C. , 2009, The journal of physical chemistry. B.

[10]  D. E. Discher,et al.  Matrix elasticity directs stem cell lineage — Soluble factors that limit osteogenesis , 2009 .

[11]  Ravi S Kane,et al.  The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells. , 2009, Biomaterials.

[12]  Ali Khademhosseini,et al.  Microengineered hydrogels for tissue engineering. , 2007, Biomaterials.

[13]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[14]  Robert Langer,et al.  A rapid-curing alginate gel system: utility in periosteum-derived cartilage tissue engineering. , 2004, Biomaterials.

[15]  Donald E Ingber,et al.  Microengineered physiological biomimicry: organs-on-chips. , 2012, Lab on a chip.

[16]  Jmrj Jacques Huyghe,et al.  Mode I crack propagation in hydrogels is step wise , 2013 .

[17]  X. Zhu,et al.  Physical models of diffusion for polymer solutions, gels and solids , 1999 .

[18]  H. Hertz.  Ueber die Berührung fester elastischer Körper. , 1882 .

[19]  D. Mooney,et al.  Independent Control of Rigidity and Toughness of Polymeric Hydrogels , 2003 .

[20]  M. Radmacher,et al.  Measuring the Elastic Properties of Thin Polymer Films with the Atomic Force Microscope , 1998 .

[21]  P. Ma,et al.  Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1. Structure, gelation rate and mechanical properties. , 2001, Biomaterials.

[22]  Ferenc Horkay,et al.  Determination of elastic moduli of thin layers of soft material using the atomic force microscope. , 2002, Biophysical journal.

[23]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[24]  Ivan Donati,et al.  Effect of Ca2+, Ba2+, and Sr2+ on alginate microbeads. , 2006, Biomacromolecules.

[25]  G. Skjåk-Bræk,et al.  Inhomogeneous polysaccharide ionic gels , 1989 .

[26]  Jing Fang,et al.  A multi-sphere indentation method to determine Young's modulus of soft polymeric materials based on the Johnson–Kendall–Roberts contact model , 2011 .

[27]  I. Donati,et al.  Specific interactions versus counterion condensation. 1. Nongelling ions/polyuronate systems. , 2006, Biomacromolecules.

[28]  I. Donati,et al.  Experimental evidence of counterion affinity in alginates: the case of nongelling ion Mg2+. , 2009, The journal of physical chemistry. B.

[29]  Achim Goepferich,et al.  Rational design of hydrogels for tissue engineering: impact of physical factors on cell behavior. , 2007, Biomaterials.

[30]  L. Chan,et al.  Cross-linking mechanisms of calcium and zinc in production of alginate microspheres. , 2002, International journal of pharmaceutics.

[31]  M. Shoichet,et al.  Stability of hydrogels used in cell encapsulation: An in vitro comparison of alginate and agarose , 1996, Biotechnology and bioengineering.

[32]  Jong Hwan Sung,et al.  A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. , 2009, Lab on a chip.

[33]  L. Grover,et al.  Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. , 2010, Acta biomaterialia.

[34]  Y. Sakai,et al.  Soluble Factor–DependentIn VitroGrowth and Maturation of Rat Fetal Liver Cells in a Three-Dimensional Culture System , 2008 .

[35]  David J Mooney,et al.  The tensile properties of alginate hydrogels. , 2004, Biomaterials.

[36]  Wim Dewulf,et al.  A test object with parallel grooves for calibration and accuracy assessment of industrial CT metrology , 2011 .

[37]  A. Mikos,et al.  Review: Hydrogels for cell immobilization , 2000, Biotechnology and bioengineering.

[38]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[39]  D. Marquardt.  An Algorithm for Least-Squares Estimation of Nonlinear Parameters , 1963 .

[40]  Wesley R. Legant,et al.  Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels , 2013, Nature materials.

[41]  David J Mooney,et al.  Alginate hydrogels as biomaterials. , 2006, Macromolecular bioscience.

[42]  Jürgen Groll,et al.  Magnesium ions and alginate do form hydrogels: a rheological study , 2012 .