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Poly(ethylene glycol) hydrogels with adaptable mechanical and degradation properties for use in biomedical applications.

ABSTRACT: Requirements of hydrogels for drug delivery, wound dressings, and surgical implantation can be extensive, including suitable mechanical properties and tailorable degradation time frames. Herein, an adaptable PEG-based hydrogel, whose mechanical properties and degradation rate can be systematically adjusted to meet these criteria by altering simple variables such as the PEG molecular weight, is described. The performance of these hydrogels in three physical manipulations (pushing, pulling, and folding), representative of manipulations that they may undergo during typical biomedical use, is also assessed. While not all of these formulations can withstand these manipulations, a subset did, and it is intended to further optimize these formulations for specific clinical applications. Additionally, the outcomes of the physical manipulation tests indicate that simply having a high modulus does not correlate with biomedical applicability.

SUBMITTER: Parlato M

PROVIDER: S-EPMC4066198 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Poly(ethylene glycol) hydrogels with adaptable mechanical and degradation properties for use in biomedical applications.

Parlato Matthew M Reichert Sarah S Barney Neal N Murphy William L WL

Macromolecular bioscience 20140125 5

Requirements of hydrogels for drug delivery, wound dressings, and surgical implantation can be extensive, including suitable mechanical properties and tailorable degradation time frames. Herein, an adaptable PEG-based hydrogel, whose mechanical properties and degradation rate can be systematically adjusted to meet these criteria by altering simple variables such as the PEG molecular weight, is described. The performance of these hydrogels in three physical manipulations (pushing, pulling, and fo ...[more]

PMID: 24949497

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Project description:Surface-associated transport of flowing bacteria, including cell rolling, is a mechanism for otherwise immobile bacteria to migrate on surfaces and could be associated with biofilm formation or the spread of infection. This work demonstrates how the moduli and/or local polymer concentration play critical roles in sustaining contact, dynamic adhesion, and transport of bacterial cells along a hydrogel or hydrated brush surface. In particular, stiffer more concentrated hydrogels and brushes maintained the greatest dynamic contact, still allowing cells to travel along the surface in flow. This study addressed how the mechanical properties, molecular architectures, and thicknesses of minimally adhesive poly(ethylene glycol) (PEG)-based coatings influence the flow-driven surface motion of Staphylococcus aureus MS2 cells. Three protein-repellant PEG-dimethylacrylate hydrogel films (∼100 μm thick) and two protein-repellant PEG brushes (8-16 nm thick) were sufficiently fouling-resistant to prevent the accumulation of flowing bacteria. However, the rolling or hopping-like motions of gently flowing S. aureus cells along the surfaces were specific to the particular hydrogel or brush, distinguishing these coatings in terms of their mechanical properties (with moduli from 2 to 1300 kPa) or local PEG concentrations (in the range 10-50% PEG). On the stiffer hydrogel coatings having higher PEG concentrations, S. aureus exhibited long runs of surface rolling, 20-50 μm in length, an increased tendency of cells to repeatedly return to some surfaces after rolling and escaping, and relatively long integrated contact times. By contrast, on the softer more dilute hydrogels, bacteria tended to encounter the surface for brief periods before escaping without return. The dynamic adhesion and motion signatures of the cells on the two brushes were bracketed by those on the soft and stiff hydrogels, demonstrating that PEG coating thickness was not important in these studies where the vertically oriented surfaces minimized the impact of gravitational forces. Control studies with similarly sized poly(ethylene oxide)-coated rigid spherical microparticles, that also did not arrest on the PEG coatings, established that the bacterial skipping and rolling signatures were specific to the S. aureus cells and not simply diffusive. Dynamic adhesion of the S. aureus cells on the PEG hydrogel surfaces correlated well with quiescent 24 h adhesion studies in the literature, despite the orientation of the flow studies that eliminated the influence of gravity on bacteria-coating normal forces.

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.

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Poly(ethylene glycol) hydrogels with adaptable mechanical and degradation properties for use in biomedical applications.

Publications

Poly(ethylene glycol) hydrogels with adaptable mechanical and degradation properties for use in biomedical applications.

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