ABSTRACT
The physiological activity of hyaluronic acid (HA) polymers and oligomers makes it a promising material for a variety of applications. The development of HA-hydrogel scaffolds with improved mechanical stability against degradation and biochemical functionality may enhance their application to tissue engineering. In this report, a crosslinking strategy targeting the alcohol groups via a poly(ethylene glycol) diepoxide crosslinker was investigated for the generation of degradable HA hydrogels. To provide support for cell adhesion in vitro, collagen was incorporated into the HA solution prior to the crosslinking process. The hydrogels have a continuous exterior and a porous interior, with pore diameters ranging from 6 to 9 microm. HA and HA-collagen hydrogels degrade in the presence of hyaluronidase and collagenase enzymes, indicating that the chemical modification does not prevent biodegradation. Complete degradation of the hydrogels occurred within 14 days in hyaluronidase (100 U/ml) and 3 days in collagenase (66 U/ml). Pattern transfer was employed to introduce a surface topography onto the hydrogel, which was able to orient cell growth. Furthermore, the hydrogels could be functionalized with the biomolecule neutravidin by incorporation of biotin along the HA backbone. This biotinylation approach may allow attachment of bioactive molecules that are conjugated to avidin.
Subject(s)
Avidin/chemistry , Cell Adhesion/physiology , Coated Materials, Biocompatible/chemistry , Collagen/chemistry , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Tissue Engineering/methods , Absorbable Implants , Adsorption , Animals , Cell Polarity , Cell Proliferation , Cross-Linking Reagents/chemistry , Elasticity , Extracellular Matrix Proteins/chemistry , Materials Testing , Mice , NIH 3T3 Cells , Protein Binding , Surface PropertiesABSTRACT
The effect of increasing confinement on soft elastic gel layers has been investigated and a means of analyzing the behavior of such systems has been developed. A probe tack test was used to study the behavior of thin elastic layers during interfacial debonding from a cylindrical glass indenter. For this gel-indenter system, confinement is defined as the ratio of a(0), the radius of the indenter, to h, the thickness of the elastic layer. In order to investigate geometric effects, the adhesion energy of the gel was kept constant while the thickness and modulus of the gels were varied. A fracture mechanics approach, based on the compliance of the layer, has been employed in analyzing the experimental data. It is shown that a fracture mechanics analysis is appropriate for these systems, allowing quantitative results to be obtained, despite very irregular contacts. It has also been shown that the interfacial instabilities observed during debonding maximize the compliance of the elastic layer. Additionally, four dimensionless parameters that dictate the behavior of confined systems have been defined, offering a general guide to understanding and characterizing the mechanical behavior of thin elastic layers.