Regenerez®: A Next-Generation Material for Functional Bioresorbable Coatings

by Carissa Smoot and Jeremy Harris, Ph.D, Secant Medical, Inc.

Coatings consisting of natural and synthetic origin play an important role in the world of medical

devices both from a functional and a biological perspective. Collagen and similar materials are

often used to coat surgical meshes to minimize the formation of intra-abdominal adhesions

following hernia repair procedures. Coatings are also applied to cardiovascular grafts to provide

a blood-tight structure until the graft is populated with host tissue. A coating made from a

material that provides a beneficial mechanical and biological response would be an invaluable

asset to medical device engineers. Regenerez®, a bioelastomer made with poly(glycerol

sebacate) (PGS) has shown tremendous promise in the field of tissue engineering and

regenerative medicine, and it is an ideal coatings candidate due to its elastomeric and

cell-friendly properties.1,2

Coating Textiles

To determine the coating properties of PGS, a variety of polymer-based textile structures were

used as substrates for coating trials. In order for PGS to adhere to the polymer, the surface

energy of the substrate must be greater than the surface energy (tension) of the coating liquid.

Common materials used in biomedical textiles include polyethylene terephthalate (PET),

polyglycolic acid (PGA), polyetheretherketone (PEEK) and polypropylene (PP). These materials

have a wide range of surface energies (mN/m)—PET (44.6), PGA (49.6), and PEEK (42.1)—and

are theoretically sufficient enough to allow wetting by PGS, which has surface energy of

42mN/m.3,4 However, materials such as PP (30.1) and PE (35.7) will have a decreased affinity

for PGS. These polymers will likely require surface modification and a potentially more advanced

coating process.3

The coating of the textile substrates was monitored using scanning electron microscopy (SEM),

and the effect on mechanical properties was determined by measuring changes in tensile

strength.

The method used to coat the higher surface energy materials (i.e., PET, PEEK and PGA) is a

standard solvent-based dip-coating process. The micrographs in Figure 1 depict samples of

PEEK, PGA and PET that were successfully coated using this process. A casting method can also

be used on these polymers to create a film of PGS that encompasses the entire textile structure.

The dip-coating and casting methods afford the ability to create films from the micron to the

millimeter scale. Whereas the casting method can only be controlled by the amount of PGS

casted, the dip-coat method can regulate coating thickness in multiple ways. One way to control

coating thickness is through the use of varying concentrations of PGS in the dip coating

solution. To illustrate the effect of dip-coating concentration, three samples of PET knit mesh

were coated with a solution of 10%, 20% and 30% PGS.

A

Figure 1. Representative SEM images comparing uncoated (A) PEEK, (B) PGA and (C) PET textiles to coated

(D) PEEK, (E) PGA and (F) PET textiles. The coating solution consisted of 20% PGS in ethyl acetate.

B C

D E F

A B C

Figure 2. Representative SEM images of PET knit mesh dip-coated with a (A) 10%, (B) 20% and (C) 30%

solution of PGS in ethyl acetate.

In Figure 2, the 10% PGS solution shows minimal PGS coating, while the 20% coating shows

the PGS beginning to bind the multifilament structure together. At 30%, the PGS coating is

thick enough to essentially create a monofilament structure out of the multifilament yarn.

In some cases, increasing the percent solids in the coating solution is not the optimal method

for increasing PGS film thickness. Another method for building coating thickness is by depositing

multiple layers of PGS (see Figure 3). This can be achieved by dip coating for a short period of

time, allowing the solvent to evaporate, and re-dipping for the same amount of time. This

process can be repeated with each layer to create a thicker PGS coating. The use of a higher

percent solids coating solution with the layering process will result in a faster build-up of PGS

than a lower percent solids solution. This is a useful method to evenly increase coating

thickness without increasing the percentage of PGS in the coating solution.

Another method for controlling coating thickness is increasing the dip time in the coating

solution. The effect of increasing dip time to increase coating thickness is most pronounced at

higher PGS concentrations. Figure 4 shows the effect of using four different dip times including

5 seconds, 2 minutes, 5 minutes and 10 minutes. The SEM images demonstrate that longer dip

A B C

D E

Figure 3. Representative SEM images of a PET woven fabric coated with (A) 1 layer, (B) 2 layers, (C) 3

layers, (D) 4 layers and (E) 5 layers of 20% PGS in ethyl acetate.

times result in increased coating thickness, which is indicated by the increased coverage of the

PET yarn filaments.

To form the elastomeric version of PGS, the resulting film must first be cured to impart the

desired level of elasticity. As the coating thickness is varied by the methods described above,

the resulting cure time also varies. For example, a longer dip time with a higher concentration

of PGS will take longer to cure than one layer deposited from a dilute solution of PGS. Therefore

the elasticity of the PGS-coated textile can be tailored by changing cure time. Longer cure times

result in a stiffer coating, whereas the minimum cure time produces a more viscoelastic coating.

Samples of PET coated in a 30% PGS in ethyl acetate solution were cured in a vacuum oven at

120°C for 3, 4, 6, 9, 10 and 13 days. Figure 5 depicts the trend of decreasing crystallization

temperature with increasing cure times, signifying an increase in PGS crosslink density.

A B C

D E

Figure 4. Representative SEM images of (A) uncoated PET woven fabric and (B) PET woven fabric coated

with a 30% PGS in ethyl acetate solution for 5 seconds, (C) 2 minutes, (D) 5 minutes and (E) 10 minutes.

Strength and Strain Testing

Tensile strength and torsional strain are two parameters used to investigate the mechanical

effect imparted by the PGS coating on the textile structures. Tensile tests were performed on

samples of uncoated and coated PET woven fabric and PET knitted mesh. Both of the coated

samples were dip-coated using a 30% PGS in ethyl acetate solution for 1 minute. In addition,

torsional testing was completed on uncoated and coated PET woven ribbon samples prepared

under the same conditions as the tensile tested samples. The tensile testing was used to

monitor the effect of the PGS coating on the maximum peak load of the textile.

-16.9

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3 5 7 9 11 13C

ryst

alliz

atio

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emp

erat

ure

(°C

)

Cure Time (Days)

40.16

72.58

118.04

142.41

0

20

40

60

80

100

120

140

160

Uncoated PET Woven Coated PET Woven Uncoated PET Knitted Coated PET Knitted

Pea

k Lo

ad (

N)

Figure 5. Graph of DSC crystallization temperature as a function of cure time.

Table 1. Peak load data from the tensile testing system for uncoated and coated

PET textiles.

The peak load that an uncoated textile structure experiences before breaking will vary

depending on its method of construction (see Table 1). However, both structures show an

increased peak load when coated with PGS. The PET woven fabric shows roughly an 80%

increase in peak load when coated with PGS, and the PET knit mesh shows an approximate

20% increase. The varied effect of the PGS coatings indicates that the peak load increase from

the PGS coating is dependent on the textile construct, because both samples were coated under

the same conditions but resulted in a different peak load increase. In addition to the increase in

peak load of the two PET samples, the failure mechanism also changed when the textile was

coated with PGS. The stress-strain curve of the uncoated samples exhibits a saw tooth pattern

as the individual filaments break prior to failure. However, the coated samples exhibited no

fluctuation prior to failure.

Break Line

Break Line

Figure 6. Representative SEM images of failure point of uncoated PET woven fabric after tensile testing.

Figure 7. Representative SEM images of failure point of coated PET woven fabric after tensile testing.

SEM images of the uncoated PET woven fabric following tensile testing show that the area of

the break is frayed and jagged (see Figure 6). The images of the break point of the coated PET

woven fabric show a clean, even break (see Figure 7) as a result of the PGS binding the

multifilament structure into a larger, stronger monofilament structure. Instead of the individual

filaments bearing the load separately, the PGS enables the filaments to work together,

dispersing the tensile load over a larger area.

The increase in peak load with the PGS coating suggests the PET textile has increased stiffness,

however, torsional testing indicates the PGS coating imparts elasticity to the textile. Using a

rheometer fitted with a torsional testing apparatus, amplitude sweeps can be performed on

samples with largely solid character. Amplitude sweeps measure storage modulus (solid

character) and loss modulus (liquid character) as a function of strain. In this case, the term

strain refers to the ratio of the deflection path of the tool to the distance between the two tools,

or the sample height. The test is conducted by securing a strip of uncoated or coated textile

between two clamps and oscillating to achieve the appropriate percentage of strain. Figure 8

depicts an amplitude sweep taken on an uncoated and 30% PGS coated sample of PET woven

ribbon.

1.0E+06

1.0E+07

1.0E+08

1.0E+09

1.0E+10

1.0E+11

0.001 0.01 0.1 1

Mo

du

lus

(Pa)

Strain (%)

Figure 8. Amplitude sweep of uncoated (blue) and PGS coated (red) PET woven ribbon. Triangles and

squares represent G” (loss modulus) and G’ (storage modulus), respectively.

The higher storage and loss modulus values for the uncoated woven ribbon indicate the sample

is more stiff and rigid compared to the coated sample. For the coated sample, the lower storage

and loss modulus values signify that the PGS coating creates more of a flexible, viscoelastic

material. The amplitude sweep of a thermoset PGS sample (Figure 9) shows the linearity of the

modulus values over the same strains, much like the response observed in Figure 8 of the

coated PET woven ribbon. This result supports the concept that the PGS coating is responsible

for the rheological response of the coated textile.

In addition, the amplitude sweep data in Figure 8 illustrates the ability of PGS to better maintain

the structure of the textile, similar to the effects seen in the tensile testing of the coated

sample. This occurrence is shown in the increase of storage and loss modulus around 0.5%

strain in the uncoated sample, but not in the coated sample. This event occurs due to the

crinkling or the disruption of the uncoated textile structure (see Figure 10).

1.0E+04

1.0E+05

1.0E+06

0.01 0.1 1

Mo

du

lus

(Pa)

Strain (%)

Figure 9. Amplitude sweep of thermoset PGS. Triangles and squares represent G” (loss modulus) and G’

(storage modulus), respectively.

The image of the woven fabric sample in Figure 10 (C and D) shows an uncoated and coated

sample that was subjected to an even larger amount of strain than the PET woven ribbon

described in Figure 10 (A and B). Consequently, the difference between these two uncoated

samples is more drastic, but the coated samples maintain their structure in both examples.

Furthermore, the decrease in modulus values seen at higher strains is indicative of the sample

reaching its yield strain, or the point in which the structure begins to break down. In the

amplitude sweep of the uncoated and coated PET woven ribbon, the storage modulus values of

the coated samples remain more linear to higher strain values than the uncoated sample,

further supporting that PGS helps to better maintain the textile’s integrity.

In Vitro Degradation Results

In order to investigate the degradation behavior of PGS as a coating, a degradation study of

PGS-coated PET woven fabric was conducted. A series of samples with increasing PGS film

thicknesses were prepared to more specifically see how coating thickness affects degradation

rate. Varied coating thicknesses were achieved with a 10% PGS coating solution, a 20%

solution and a 30% solution using three different dip times, and a thick film sample achieved by

the neat method. The graph in Figure 11 depicts the average PGS coating masses for each film

thickness.

A B

C D

Figure 10. Images of (A) coated PET woven ribbon, (B) uncoated PET woven ribbon, (C) uncoated PET

woven fabric and (D) coated PET woven fabric after torison testing.

Eight samples of each coating thickness were prepared to remove one sample at eight different

time points. The samples were placed in sterilized petri dishes and soaked in 0.5 M PBS

(pH=7.4) in an incubator set at 37.0°C. At the designated time point, the samples were rinsed

and dried until a constant mass was obtained. Each sample was then observed by SEM to

determine changes in surface morphology due to degradation. Mass loss values for each of the

samples over a two-week period are shown in Table 2. The percent mass loss at each time

point is fairly consistent for the 20% and 30% samples, regardless of dip time. The thick film

sample lost less PGS during Week 1, which can be explained by surface area. The dip-coated

samples have a thin film of PGS that conformally coats the individual filaments, resulting in a

larger surface area. The thick film is a solid block of PGS, resulting in a smaller amount of

exposed surface area.

Sample % Mass Loss

Week 1 % Mass Loss

Week 2

20% 13.64 15.00

30% 5 sec 14.37 14.06

30% 5 min 12.50 16.37

30% 10 min 12.27 12.99

Thick Film 6.86 No Sample Removed

9.1 15.6 21.5 22.7

252.3

0

50

100

150

200

250

Co

atin

g M

ass

(mg)

Figure 11. Average PGS coating mass values for each film thickness.

Table 2. Degradation Mass Loss Results at Week 1 and Week 2

20% 30% 5 sec 30% 5 min 30% 10 min Thick Film

Although not by a large amount, the percent mass loss in Week 2 is slightly higher for most of

the degradation samples. One of the advantages of PGS over other resorbable biomaterials is

that PGS undergoes surface erosion as opposed to bulk erosion during degradation. Figure 12

shows that the surface erosion mechanism holds even when PGS is used as a coating.

The SEM micrographs show the emergence of the underlying filaments of the weave structure

and more of the top-layer filaments, indicating that the PGS coating is degrading. Future studies

to further investigate the degradation profile of PGS on PET will include FTIR microscope

analysis.

Conclusion

As the demand for performance and biocompatibility in medical devices continues to increase,

so will the need for devices that are more biologically and physically compliant. Coatings

technology provides a bolt-on technology for materials commonly used in medical devices, as

they have already have shown utility in improving the biological and physical properties of

finished devices. As a coating, PGS has tremendous potential based on its ability to uniformly

coat multiple polymeric materials in a controlled and reproducible manner. The PGS coating

enhanced the mechanical properties of the coated textile by increasing the maximum tensile

load and elasticity of the construct. Early degradation study results show that the PGS coating is

degrading through a surface erosion mechanism that is consistent with other studies. Future

work includes continued degradation studies and determining release kinetics of drug-loaded

PGS coatings.

Figure 12. Representative SEM images of PET woven fabric. These images show only a small portion of the

sample, but this observation was observed throughout the entire sample.

(A) uncoated, (B) 30% 10-minute coated after 1 week degradation and (C) 30% 10-minute coated after 2 weeks

degradation

A B C

References

1. Wang, Y., Ameer, G.A., Sheppard, B.J., and Langer, R. (2002). A tough biodegradable elastomer. Nature

Biotechnology 20(6), 602-606.

2. Rai, R., Tallawi, M., Grigore, A., Boccaccini, A.R. (2012) Synthesis, properties and biomedical applications of

poly(glycerol sebacate) (PGS): a review. Progress in Polymer Science 37(8), 1051-1078.

3. Solid surface energy data (SFE) for common polymers. Retrieved from: http://www.surface-tension.de/solid-

surface-energy.htm.

4. Rai, R. et. al. (2013). Materials Science and Engineering C33, 3677.

Jeremy Harris, Ph.D., is technical director at Secant Medical, Inc., and Carissa Smoot is a

scientist at the company.

© 2014 Secant Medical®, Inc. The information contained herein is subject to change without notice. Secant Medical

shall not be liable for technical or editorial errors or omissions contained herein.

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