The Effect of Hydrophobicity on the Viscoelastic Creep Characteristics

Chapter 16

The Effect of Hydrophobicity on the Viscoelastic Creep Characteristics of Poly(ethylene glycol)-Acrylate Hydrogels 1-3

Downloaded by YORK UNIV on September 21, 2016 | http://pubs.acs.org Publication Date: October 15, 2002 | doi: 10.1021/bk-2002-0833.ch016

N.

3

Ravi ,

4

2

A. Mitra , L. Zhang , P. Kannan , and B. A. Szabó

4

Department of Surgery, VA Medical Center, St. Louis, MO 63106

1

Departments of Ophthalmology and 2

4

and Mechanical Engineering,

Visual

Washington

Sciences,

University,

3

Chemical

St.

Louis,

Engineering, MO

63110

The creep behavior of hydrophobic poly(ethylene glycol)acrylate hydrogels was well characterized by two Kelvin units in series, compared to the other various combinations of the linear viscoelastic elements investigated. The hydrogels were synthesized by reacting acrylate derivatives of poly(ethylene glycol) [PEG] with PEG-diacrylate as the crosslinking agent. By using different amounts ofω-phenoxy-PEG-acrylatein the monomer feed ratio, the hydrophobicity was varied. The extent of monomer conversion was greater than 95%, as determined by Raman spectroscopy. With increasing hydrophobicity, the elastic modulus of the hydrogels increased from 10.92 kPa to 35.10 kPa, and the density increased from 1.0004 g/cm to 1.0091 g/cm , while the dimensional stability decreased from 1.55 to 1.48. Two Kelvin units in series well characterized the creep curve for various loads and time durations. The time constants were in the range of 1-2 s and approximately 300 s for the two Kelvin units. These hydrophobic hydrogels may be used as model tissues to determine the viscoelasticity of the human lens. 3

3

233

© 2003 American Chemical Society Bohidar et al.; Polymer Gels ACS Symposium Series; American Chemical Society: Washington, DC, 2002.

234


Introduction Hydrogels are extensively used as biomaterials in biology and medicine (75), scaffolds in tissue engineering (6), and adjuvants in drug delivery (7-9). In ophthalmology, hydrogels are not only used for soft contact lenses, but also as vitreous, corneal, and lenticular substitutes (10-14). We plan to use hydrogels as model tissues for understanding the biomechanics of accommodation and presbyopia (75). The function of the normal eye is to form clear retinal images of objects, irrespective of the distance. To form focussed images requires the molding of the lens substance by several tissues. This process of altering the lenticular refractive power to see clearly at near is referred to as accommodation (16). However, by the fourth decade of life, accommodation begins to fail and the condition known as presbyopia sets in. Age-related changes in the ciliary body (77,78), lens capsule (19,20), neuro-sensory system (27), and the lens substance (22-25) have all been implicated in the pathogenesis of presbyopia. Recent evidence however indicates that the lens may be the primary cause of presbyopia (23). The lens fiber matrix, enclosed within the capsular bag, is a collection of well-organized lens fibers whose cytoplasm is rich in proteins. Thus, the whole lens is analogous to a fiber-reinforced viscoelastic composite within an elastic aspheric biconvex capsular bag. The elastic modulus of the lens has been determined to range from 0.75 kPa to 10.9 kPa depending on the age of the lens and the technique used (19,25-29). Our ultimate goal is to develop a robust axisymmetric finite element model for accommodation and presbyopia. However, one must first determine the biomechanical characteristics of the tissues involved in accommodation, particularly of the lens. The lens itself has a complex geometry, which makes determination of the stress difficult. Hence, to determine the stress deformation characteristics of a system with simpler geometry, cylindrical disc shaped synthetic hydrogels with comparable elastic properties were investigated. PEG-based hydrogels assume importance due to their unique solubility characteristics and biocompatibility (30,31). Furthermore, they are readily available commercially and can be easily modified. In our earlier work (75), we determined that co-hydroxy-PEG-methacrylate hydrogels exhibit an elastic modulus of 8-20 kPa. In this study, we hypothesized that the replacement of the co-hydroxy pendant group would result in a lower elastic modulus due to the absence of hydrogen bonding. Thus, we investigated hydrogels derived from u> methoxy-PEG-acrylate with PEG-diacrylate as the crosslinking agent. In order to evaluate the effect of hydrophobicity, we incorporated o>phenoxy-PEG-acrylate

Bohidar et al.; Polymer Gels ACS Symposium Series; American Chemical Society: Washington, DC, 2002.

235 in this system. The effect of monomer feed ratio on the creep-recovery and dimensional stability of hydrogels equilibrated in water was evaluated.

Experimental


Materials The monomers used were G>-methoxy-poly(ethylene glycol)-acrylate [coCH -PEG-Ac] and co-phenoxy-poly(ethylene glycol)-acrylate [co-Ph-PEG-Ac]. The crosslinking agent was poly(ethylene glycol)-diacrylate [PEGDAc]. The reagents used were N, N, N \ N' tetramethylethylene diamine [TEMED] and ammonium persulfate [APS]. 0>CH -PEG-Ac was received from Polysciences and TEMED from Sigma Chemicals. The rest of the chemicals were purchased from Aldrich Chemical Corp. All of the chemicals were used as received. 3

3

Characterization of Monomers The number average molecular weights [M ] of the PEG segment in G>CH PEG-Ac, ©-Ph-PEG-Ac, and PEGDAc were 400, 340, and 400 Daltons respectively (as reported by the supplier). The molecular weight distribution of the monomers was obtained by mass-spectroscopy (MALDI - T O F MS) using a 377 nm nitrogen laser for desorption of ions adsorbed onto a-cyano-4hydroxycinnamic acid matrix. The amount of sample added was 0.1-1% and was varied to maximize the signal. Acetonitrile-water mixture served as the solvent for both the sample as well as the matrix. The masses of the oligomeric peaks obtained from the calibrated spectra, combined with their relative intensities (height or counts), allowed for the calculation of M and M . The monomers were characterized by FTIR and Raman spectroscopy (LabRam; Horiba Group). n

3

n

w

Hydrogel Preparation The gels were prepared using varying amounts of the two monomers, keeping the total weight constant at 2 g. Three grams of solvent (EtOH : H 0 at 25 : 75 w/w ratio) was added to this mixture. Therefore, all of the samples were 2


236 at 40% w/w solids. The final hydrogels [HG] were described by HG-X-Y-Z where X, Y, and Z are the initial monomer weight percent of 00-CH3-PEGacrylate, G>-Ph-PEG-acrylate, and PEG-diacrylate respectively. The process for synthesizing the hydrophobic hydrogels is represented below:

(X

)

( Y

C H f = C H

)

C H f = C H

C = 0

(Z )


P E G D A I f C H

C H I 1| 1

2

2

n

2

0 1 C H

^

y +

H2

H Y D R O P H O B I C

T E M E D A P S EtOH:H 0

H Y D R O G E L

2

( 25:75^ 3

Scheme 1. Synthesis of hydrophobic hydrogels.

As an example, the synthesis of the hydrogel HG-83-15-02 was carried out as follows: To 00-CH3-PEG-AC (1.66 g), the crosslinking agent [PEGDAc (0.04 g)] was added, followed by the addition of o-Ph-PEG-Ac (0.30 g). The contents were thoroughly mixed until a uniform mixture was obtained. Three grams of the solvent [EtOH:H 0::l:3] was added slowly with continuous stirring to form a 40% w/w clear solution. TEMED (10 and freshly prepared APS (10% w/w solution) were added to this solution and mixed thoroughly. No attempts were made to remove oxygen or inhibitors. The solution was poured into a glass mold (10 x 8 x 0.45 cm) formed by two glass sheets separated with spacers along three sides and securely held in position with clamps. Polymerization and gelation was carried out for 24 hours. The hydrogel was subsequently removedfromthe mold and carefully submerged in MilliQ water (200 ml). The water was changed twice a day for 5 days to remove the unreacted monomer. 2

Characterization of Hydrogels The density of the hydrogel was calculated using a high precision weighing balance equipped with a density measurement kit. After measuring the weight of


237 the sample in air and in dodecane, and using the density of dodecane, the density of the sample was obtained as described by Peppas (7). Measurements were carried out on five samples and the average and standard deviation were determined.

Raman Spectroscopy


Aliquots of the monomers (neat) were placed on microscope slides. A Raman spectrometer (LabRam) equipped with a He-Ne laser and coupled to an optical microscope was used to obtain the Raman signals. GRAMS/32 (Galactic Industries) software was used to analyze and display the spectra.

Mechanical Properties Mechanical properties were determined using a dynamic mechanical analyzer (Perkin Elmer DMA 7e). A cylindrical disc shaped sample, 1 cm in diameter and 0.6 cm thick was placed between parallel plates in an environment chamber containing 3 ml of MilliQ water, maintained at 37°C. The sample was allowed to equilibrate at zero load for 300 s and its height was measured. A constant load was then applied rapidly and the sample was allowed to creep for 300 s to 2700 s. By this time, the sample strain was assumed to have reached equilibrium. The experiment was performed with varying loads using a new sample for each test. The instrument compliance was less than 0.01% of the sample's compliance and hence no correction was required. The strain at the end of 60 s was considered for the stress-strain plot, the slope of which gives the elastic modulus (E). The shear modulus, G, for low strains (

The Effect of Hydrophobicity on the Viscoelastic Creep Characteristics

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