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Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels.

ABSTRACT: The elastic modulus of the extracellular matrix is a dynamic property that changes during various biological processes, such as disease progression or wound healing. Most cell culture platforms, however, have traditionally exhibited static properties, making it necessary to replate cells to study the effects of different elastic moduli on cell phenotype. Recently, much progress has been made in the development of substrates with mechanisms for either increasing or decreasing stiffness in situ, but there are fewer examples of substrates that can both stiffen and soften, which may be important for simulating the effects of repeated ECM injury and resolution. In the work presented here, poly(ethylene glycol)-based hydrogels reversibly stiffen and soften with multiple light stimuli via photoisomerization of an azobenzene-containing cross-linker. Upon irradiation with cytocompatible doses of 365 nm light (10 mW/cm(2), 5 min), isomerization to the azobenzene cis configuration leads to a softening of the hydrogel up to 100-200 Pa (shear storage modulus, G'). This change in gel properties is maintained over a time scale of several hours due to the long half-life of the cis isomer. The initial modulus of the gel can be recovered upon irradiation with similar doses of visible light. With applications in mechanobiology in mind, cytocompatibility with a mechanoresponsive primary cell type is demonstrated. Porcine aortic valvular interstitial cells were encapsulated in the developed hydrogels and shown to exhibit high levels of survival, as well as a spread morphology. The developed hydrogels enable a route to the noninvasive control of substrate modulus independent of changes in the chemical composition or network connectivity, allowing for investigations of the effect of dynamic matrix stiffness on adhered cell behavior.

SUBMITTER: Rosales AM

PROVIDER: S-EPMC4547937 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels.

Rosales Adrianne M AM Mabry Kelly M KM Nehls Eric Michael EM Anseth Kristi S KS

Biomacromolecules 20150210 3

The elastic modulus of the extracellular matrix is a dynamic property that changes during various biological processes, such as disease progression or wound healing. Most cell culture platforms, however, have traditionally exhibited static properties, making it necessary to replate cells to study the effects of different elastic moduli on cell phenotype. Recently, much progress has been made in the development of substrates with mechanisms for either increasing or decreasing stiffness in situ, b ...[more]

PMID: 25629423

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Project description:Growth factors have been shown to be potent mediators of osteogenesis. However, their use in tissue-engineered scaffolds not only can be costly but also can induce undesired responses in surrounding tissues. Thus, the ability to specifically induce osteogenic differentiation in the absence of exogenous growth factors through manipulation of scaffold material properties would be desirable for bone regeneration. Previous research indicates that addition of inorganic or hydrophobic components to organic, hydrophilic scaffolds can enhance multipotent stem cell (MSC) osteogenesis. However, the combined impact of scaffold inorganic content and hydrophobicity on MSC behavior has not been systematically explored, particularly in three-dimensional (3D) culture systems. The aim of the present study was therefore to examine the effects of simultaneous increases in scaffold hydrophobicity and inorganic content on MSC osteogenic fate decisions in a 3D culture environment toward the development of intrinsically osteoinductive scaffolds. Mouse 10T½ MSCs were encapsulated in a series of novel scaffolds composed of varying levels of hydrophobic, inorganic poly(dimethylsiloxane) (PDMS) and hydrophilic, organic poly(ethylene glycol) (PEG). After 21 days of culture, increased levels of osteoblast markers, runx2 and osteocalcin, were observed in scaffolds with increased PDMS content. Bone extracellular matrix (ECM) molecules, collagen I and calcium phosphate, were also elevated in formulations with higher PDMS:PEG ratios. Importantly, this osteogenic response appeared to be specific in that markers for chondrocytic, smooth muscle cell, and adipocytic lineages were not similarly affected by variations in scaffold PDMS content. As anticipated, the increase in scaffold hydrophobicity accompanying increasing PDMS levels was associated with elevated scaffold serum protein adsorption. Thus, scaffold inorganic content combined with alterations in adsorbed serum proteins may underlie the observed cell behavior.

Dataset Information

Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels.

Publications

Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels.

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