Showing papers by "Ovijit Chaudhuri published in 2015"

Substrate stress relaxation regulates cell spreading

Abstract: Studies of cellular mechanotransduction have converged upon the idea that cells sense extracellular matrix (ECM) elasticity by gauging resistance to the traction forces they exert on the ECM. However, these studies typically utilize purely elastic materials as substrates, whereas physiological ECMs are viscoelastic, and exhibit stress relaxation, so that cellular traction forces exerted by cells remodel the ECM. Here we investigate the influence of ECM stress relaxation on cell behaviour through computational modelling and cellular experiments. Surprisingly, both our computational model and experiments find that spreading for cells cultured on soft substrates that exhibit stress relaxation is greater than cells spreading on elastic substrates of the same modulus, but similar to that of cells spreading on stiffer elastic substrates. These findings challenge the current view of how cells sense and respond to the ECM.

Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

Abstract: The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

Biological materials and molecular biomimetics – filling up the empty soft materials space for tissue engineering applications

Abstract: An extensive range of biomaterials, frequently derived from extracellular matrix (ECM) proteins or other natural biopolymers, have been developed for biomedical applications. Their mechanical response, a key requirement for regenerative medicine, is often stiff but exhibits limited extensibility (e.g. silk), or inversely, is compliant with higher strain to failure (e.g. elastin). While synthetic biocompatible materials exhibiting a mechanical response between these boundaries are rare, several biological materials demonstrate unexpected combinations of these properties. In order to replicate these performance metrics in synthetic systems, a central requirement is to first reveal the molecular design of their constituent building blocks, which has traditionally been an extremely time-consuming task. Here, we highlight the recent application of Next Gen sequencing technologies for the characterization of several protein-based natural biopolymers, a technique which circumvents this research bottleneck. Successful molecular biomimicry of these model protein systems could thus have the potential to significantly expand the range of intrinsic material properties available for biomedical applications.

Interpenetrating network hydrogels with independently tunable stiffness

Abstract: Interpenetrating network hydrogels with independently tunable stiffness enhance tissue regeneration and wound healing.

Viscoelastic hydrogels with fast stress relaxation

Abstract: Provided are fast relaxing hydrogels that are useful for regulating cell behavior and enhancing tissue regeneration, e.g., bone regeneration.