Simultaneous improvement of oxidative and hydrolytic resistance of

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Simultaneous improvement of oxidative and hydrolytic resistance of polycarbonate urethanes based on polydimethylsiloxane/ poly(hexamethylene carbonate) mixed macrodiols Zhen Li, Jian Yang, Heng Ye, Mingming Ding, Feng Luo, Jianshu Li, Jiehua Li, Hong Tan, and Qiang Fu Biomacromolecules, Just Accepted Manuscript • DOI: 10.1021/acs.biomac.8b00234 • Publication Date (Web): 18 Apr 2018 Downloaded from http://pubs.acs.org on April 19, 2018

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Biomacromolecules

Simultaneous

improvement

of

oxidative

and

hydrolytic resistance of polycarbonate urethanes based on polydimethylsiloxane/ poly(hexamethylene carbonate) mixed macrodiols Zhen Li, Jian Yang, Heng Ye, Mingming Ding, Feng Luo, Jianshu Li, Jiehua Li*, Hong Tan* and Qiang Fu College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China Keywords. Polycarbonate urethanes, Polydimethylsiloxane, Oxidation, Hydrolysis, Surface properties

Abstract. The degradation behaviors including oxidation and hydrolysis of silicone modified polycarbonate urethanes were thoroughly investigated. These polyurethanes were based on poly hexamethylene carbonate (PHMC) /polydimethylsiloxane (PDMS) mixed macrodiols with molar ratio of PDMS ranging from 5% to 30%. It was proved that PDMS tended to migrate toward surface and even a small amount of PDMS could form a silicone-like surface. Macrophagesmediated oxidation process indicated that the PDMS surface layer was desirable to protect the fragile soft PHMC from the attack of degradative species. Hydrolysis process was probed in

ACS Paragon Plus Environment

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detail after immersing in boiling buffered water using combined analytical tools. Hydrolytically stable PDMS could act as protective shields for the bulk to hinder the chain scission of polycarbonate carbonyls whereas the hydrolysis of urethane linkages was less affected. Although the promoted phase separation at higher PDMS fractions lead to possible physical defects and mechanical compromise after degradation, simultaneously enhanced oxidation and hydrolysis resistance could be achieved for the polyurethanes with proper PDMS incorporation.

Introduction Polyurethanes (PUs) are block copolymers comprising soft segments (SS) and hard segments (HS). Via tuning the chemical composition of HS and SS, versatile PUs could be obtained with a combination of excellent mechanical properties, good biocompatibility as well as processability, making them promising candidates in biomedical applications.1-3 Particularly, the documented strength, durability, flexibility, and biostability extend the use of PUs in long term implantable medical devices. However, PUs were observed to be degraded in vivo mainly through hydrolytic and oxidative degradation.4 Polyesterurethanes (PESUs) suffered from hydrolytic degradation of ester groups while polyetherurethanes (PEUs) are susceptible to oxidative degradation of polyether segment.5-10 Polycarbonate urethanes (PCUs) are designed as more biostable materials compared with PESUs and PEUs. Nevertheless, evidences of hydrolytic or oxidative degradation of PCU were still traced in recent studies.11-13 To further improve the biostability of PCUs, PDMS has been incorporated to replace part of susceptible polyether or polycarbonate soft segment.14-22 For example, the commercially available PDMS modified PCUs (trade mark CarboSil) have been developed using mixed macrodiols of poly(hexamethylene carbonate) (PHMC) and PDMS.23-25 To serve as long-term implantation material, the biodegradation of PDMS modified PCU is gaining broad interest.


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Oxidative degradation occurs at surface and is mainly determined by the local macrophage environment. Normally, the implanted devices are too large for macrophages to phagocytize, therefore the macrophages tend to adhere and fuse on the material surface to form the foreign body giant cells (FBGCs). The tightly adherent macrophages and FBGCs promote the production of acids, enzymes as well as reactive oxygen intermediates (ROIs) at the interface of the cells and materials, among which ROIs are deemed as the most destructive and vital oxidative species for implanted devices.26 Numerous tests mimicking the in vivo physiological degradation were conducted to validate the enhanced oxidative stability of PDMS-PEUs.22, 27, 28 With regard to PDMS-PCUs, fewer studies were reported. Some work has been performed to validate the oxidative behavior of PCUs treated in the actual biologic environment mediated directly by macrophages.

24, 25

However, these studies focused mainly on the macrophage adhesion and

fusion behavior and rarely concerned the oxidative degradation process of PDMS-PCU. The response of silicone-modified PCU with multiple compositions to macrophages-released ROIs and its anti-oxidation identity deserve further investigation. Oxidation is initiated by attacking the soft segment of both PEU and PCU, while hydrolytic degradation has been proven to occur at the urethane linkage of PEU and both carbonates and urethane bonds of PCU.29, 30 Since contact with water is inevitable whether after implantation or during steam sterilization of materials, more efforts have been devoted to the hydrolytic stability of PUs considering the fast rate of water diffusion.18, 29, 31-34 Although the substitution of PDMS for weak soft segment contributed to improved oxidation resistance, it is uncertain whether the hydrolytic stability of PUs can be enhanced as well since the hydrolysis cleavages could be initiated at urethane bonds. K.A. Chaffin et al. observed molar mass reduction in temperature accelerated test accompanied with reduction of tensile strength as well as abrasion and fatigue


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resistance. Unexpectedly, they pointed out that PEU containing PDMS underwent more rapid molar mass reduction than controlled PEU due to uncertain hydrolytic cleavage of backbone.18, 29, 34

Cosgriff-Hernandez, E. et al. ascribed the accelerated hydrolysis of PDMS-PEU to

undesirable phase separation or thermal dissociation of allophanate groups.32,

33

Unlike PEU

where the hydrolytic chain cleavages are initiated only in urethane linkage, PCU has two cleavage sites: carbonate and urethane linkages.35 Hydrolytic process is more complicated after incorporation of PDMS in soft segment. However, the study on hydrolysis mechanism and corresponding structure-property evolutions of PDMS-PCUs has been rarely reported to date. In this work，we investigate the biostability of PDMS-PCUs by evaluating their oxidative and hydrolytic degradation behaviors. The PU samples were exposed in macrophage mediated micro-environment and deoxygenated phosphate buffered saline (PBS) solution and the surface properties and micro domain structures of PDMS-PCUs were carefully characterized. Furthermore, the correlation between surface structures and degradation process were established to clarify the biodegradation mechanism of PDMS-PCUs.

Experimental section Materials Poly(hexamethylene carbonate) (PHMC) diol (MW 1000) was purchased from Ube Japan and dehydrated under reduce pressure. Polydimethylsiloxane (PDMS) diol (MW 2000) was kindly supplied by Degussa Co. Shanghai, China. 4,4′-Methylenediphenyl diisocyanate (MDI) and 1,4butanediol (BDO) were purchased from Wanhua Chemical Group Co., Ltd, China and Flaka chemika, Switzerland respectively. They were distilled under vacuum before used. N,Ndimethylacetamide (DMAc) was distilled after drying with calcium hydride for 2 d. Sample preparation


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A series of PDMS modified PCUs were synthesized in our lab as reported previously.36 For short, hard segments are constructed by MDI and BDO and soft segments consist of mixed polyols of PDMS and PHMC. The samples are denoted as PDMSx-PCU, where x represents the molar ratio of PDMS in the mixed macrodiols. The obtained polymers were dissolved in DMAc and 10% (W/V) solution were then cast into films of 0.3 mm thickness. The films were dried under vacuum at elevated temperature until the total removal of DMAc before evaluation. Material characterization Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra were conducted on the cast films using Nicolet-560 FTIR spectrometer. Each sample was scanned with a resolution of 4 cm-1 for 32 times in 4000-600 cm-1. Elemental analysis of the sample surface was realized by X-ray photo electron spectroscopic analysis (XPS), carried out on an XSAM-800 electron spectrometer with X-ray radiation from Mg Kα source (20 Kv, 10 mA). The take-off angle was 30° and 90°. Contact angles (CA) were conducted on a DSA-100 (Krüss GmbH ， Hamburg, Germany) goniometer using 3µL distilled-deionized water. The surfaces before and after treatment were examined by scanning electron microscopy (SEM), which was carried out on an FEI Inspect F SEM instrument using an acceleration voltage of 20 kV. The films were sputter-coating with gold powder before observation. Relative molecular weight were monitored by Waters-1515 Gel Permeation Chromatography (GPC). The samples were dissolved in DMF/LiBr solution with concentration of 2-3 mg/ml. The flow rate of the solution was 1.0 ml/min at 40°C. Molar mass was obtained by calibrating with linear PMMA standards and the relative molar mass was not converted to absolute scale for comparison with the published results.18,29,31


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H NMR spectra were acquired on Varian unity Inova-400 spectrometer (400 MHz) at room

temperature, using DMSO-d6 as solvents and tetramethylsilane (TMS) as internal standard. Tensile properties were measured on Instron 4302 universal testing machine. The tensile speed was 500 mm/min maintained at 23 °C and 50 % relative humidity. Macrophages mediated oxidative degradation The macrophages mediated oxidative degradation of PDMS-PCU was carried out via culture of macrophages on the cast films. RAW 264.7 macrophages were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 100 U/ml of streptomycin, 100 U/ml of penicillin and 10% fetal bovine serum (FBS). The culture was renewed after 2 d and digested by 0.25% of trypsin. The cells were seeded on the PDMS-PCU films in 6-well plate after centrifuged and sterilized. After incubating for 1, 7 and 21 d respectively, the film adherent with macrophages were fixed in 2% glutaraldehyde for 2 hrs. The macrophages were removed by TrypsinEDTA from the samples after 21 d of incubation and the left PDMS-PCU films were also fixed in glutaraldehyde. Then the samples were rinsed 3 times by phosphate buffered saline (PBS) followed by 25%, 50%, 75%, 90% and 100% v/v ethanol rinsing for 2 times. The films were vacuum dried before examination with GPC and SEM to evaluate molecular weight changes and surface pitting. Hydrolysis in PBS PDMS-PCU films were immersed in PBS solution where the presence of oxygen was minimized by pumping into nitrogen and aged at 100 °C for 12 h one day and up to 28 d. The films were removed from PBS solution periodically (0 d, 7 d, 14 d, 21 d and 28 d), rinsed by PBS for 3 times and dried under reduced pressure at 50 °C for 12 h. For each sampling time point, the specimens were denoted as PDMSx-PCU-y, where x and y respectively represented the molar


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ratio of PDMS in the soft segment and hydrolysis days in PBS. Aged films were further characterized by SEM, WCA, ATR-FTIR, GPC, and tensile test. Particularly, 1H NMR spectroscopy was used to analysis structure changes of solid polymer before and after aging for 28 d. 1H NMR spectra of the degradation residuals in PBS solution were also recorded to detect the molecular structures.

Results and discussion Surface chemistry The replacement of susceptible polyether or polycarbonate soft segment with PDMS could give PUs silicone-like surface and thus increases its biostability.37 Therefore, the surface properties of PDMS-PCU were firstly evaluated to correlate the unique structures with oxidation and hydrolysis behavior. ATR-FTIR is one of the most effective techniques to detect the surface chemical composition and morphological structures of polymers. As shown in Figure 1, the peak intensity of PDMS-PCU at 1256, 1015-1065 and 790 cm-1 assigned to the symmetric CH3 bending band, Si-O-Si stretching band and Si-CH3 rocking band, respectively,38 were found increased with increasing of PDMS content compared with those of PCU. The result indicates that controlled amounts of PDMS-diols have been copolymerized with PCU-diol.


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Figure 1 ATR-FTIR spectra of PDMS-PCU

The surface chemistry of PDMS-PCU was analyzed by XPS. The take-off angles of 30° and 90° were corresponded to the element detection in the depth of 5 nm (top-layer) and 10 nm (sublayer) respectively. Surface atomic concentration of nitrogen (N) and silicone (Si) represent the fraction of hard segment and PDMS, respectively. After introduction of PDMS, Si element was immediately detected and the Si concentration on the surface of PDMS-PCU was higher than that in the bulk (table1). For all the samples Si content detected at 90° was higher than 30°, indicating that PDMS tended to accumulate at sub-layer. As the fraction of incorporated PDMS in soft segment increased, the percentage of Si elements in the top layer increased while those in the sub layer remained unchanged. The enrichment of Si in both top-layer and sub-layer reached to a saturated state with the content of PDMS up to 20%.


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Table 1 XPS results of PCU and PDMS-PCU Sample

angle

C

N

N (bulk)

O

Si

(theoretical) PCU

PDMS5%-PCU

PDMS10%-PCU

PDMS20%-PCU

PDMS30%-PCU

30°

71.0%

3.1%

90°

71.7%

2.7%

30°

63.3%

2.5%

90°

59.7%

1.5%

30°

63.5%

2.8%

90°

59.8%

1.6%

30°

61.9%

2.1%

90°

59.5%

1.4%

30°

61.8%

2.2%

90°

60.6%

1.8%

3.60

3.30

3.24

2.97

2.76

Si (bulk) (theoretical)

25.9%

0

25.6%

0

24.8%

9.4%

24.3%

14.6

24.1%

9.6%

23.7%

14.9%

24.5%

11.5%

24.4%

14.7%

24.6%

11.5%

23.7%

13.9%

0

2.49

4.58

7.91

10.43

In vitro cell-mediated oxidation The oxidative degradation was preceded via culturing casting films with seeded macrophages.

39

After incubation for 1, 7 and 21 d, macrophages adhering on the film were

imaged by SEM. It was found that the morphologies and densities of adherent macrophages did not differ significantly between silicone-modified PCU and control PCU (Figure 2 and Figure S1). Macrophages tended to aggregate on the surface of both PDMS modified PCU and unmodified PCU. The result indicates that hydrophobic surfaces had no obvious effects on macrophage adhesion, which is in good agreement with previous findings in silicone modified PU.24, 25


9


PCU

PCU5%-PCU

PCU20%-PCU

PCU30%-PCU

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PCU10%-PCU

Figure 2 SEM images of cell-treated PDMS-PCU cultured with cells after 21 d.

The surface morphologies of the films were observed after removing the adhered macrophages. In Figure 3, surface pitting appeared for control PCU, ascribed to the extraction of degradation products of low molecular weight after chain scission. PDMS could migrate to the surface and thus form a protective barrier to avoid the vulnerable inner components being attacked. Enhanced anti-oxidation was evidenced by the reduced pitting density and size for PDMS5%-PCU as compared with control PCU. Surface pitting was invisible for PDMS10%PCU, further confirming that the incorporation PDMS could remarkably promote the biostability of PCU. As the molar fraction of PDMS further increased to 20%, surface pitting appeared again. Particularly, tiny holes instead of obvious pitting were observed for PDMS20%-PCU and PDMS30%-PCU.


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PCU

PCU-21

PDMS5%-PCU

PDMS5%-PCU-21

PDMS10%-PCU

PDMS10%-PCU-21

PDMS20%-PCU

PDMS20%-PCU-21

PDMS30%-PCU

PDMS30%-PCU-21


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Figure 3 SEM images of trypsinEDTA -treated PDMS-PCU which were cultured with cells after 21d. The variation of molecular weight before and after macrophage treatment were determined by GPC (Table 2). Mn of control PCU decreased from 76.7 kg/mol to 58.2 kg/mol and polydispersity increased from 2.10 to 2.19. This indicates chain scission was triggered by the ROIs, enzymes and acids released by macrophages. On the other hand, silicone-modified PCU exhibited low extent of molecular weight loss with only 5 mol% of PDMS mixed in soft segment. The molecular weight of PDMS20%-PCU and PDMS30%-PCU kept almost constant after cell treatment, proving that the incorporation of PDMS into PCU significantly improve the biostability. In addition, the GPC results implied that the defects in PDMS20%-PCU and PDMS30%-PCU might not be caused by backbone cleavage. Table 2 molecular weights and molecular weight distribution of the PDMS-PCU before and after 21 d of cell treatment Sample

Mn(×104 g/mol)

Mw(×104 g/mol)

Mw/Mn

PCU

7.67

16.1

2.10

PCU-21

5.82

12.7

2.19

PDMS5%-PCU

5.41

11.7

2.16

PDMS5%-PCU-21

5.35

11.7

2.18

PDMS10%-PCU

4.46

8.61

1.92

PDMS10%-PCU-21

4.24

8.20

1.93

PDMS20%-PCU

4.21

7.92

1.87

PDMS20%-PCU-21

4.16

8.04

1.93

PDMS30%-PCU

4.44

8.64

1.94

PDMS30%-PCU-21

4.40

8.81

2.00


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Hydrolysis To the best of our knowledge, hydrolytic stability of PDMS modified PCU has been rarely reported. Detailed investigation on hydrolysis behavior was emphasized in this part. Unlike PEU hydrolysis occurring only at urethane linkage, PCUs were susceptible to hydrolysis at both urethane and carbonate bonds. The proposed cleavage sites of PCU are illustrated in Figure 4. The hydrolysis of urethane carbonyl could be divided into two steps. The first step is backbone hydrolysis which generates one chain containing terminal aromatic amine and another chain containing hydroxyl group. The second step liberates 4,4´-methylene dianiline (MDA) via the cleavage of adjacent urethane linkage. The hydrolysis of carbonate carbonyls also generates chains ended with hydroxyl groups. H N

O

H N

O

O

Step I

H N

O

O

NH2 HO

O

Step II H2N

NH2 HO

OH

Hydrolysis of urethane carbonyls O O

O

O

O

OH

OH

O

O

Hydrolysis of polycarbonate carbonyls Figure 4 Chain cleavage of urethane and polycarbonate linkages


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To confirm the cleavage sites of urethane and carbonate hydrolysis, the 1H NMR spectra of polyurethanes aged at 100 °C for 28 d in PBS are presented in Figure 5 and Figure S2, taking sample without PBS treatment as a control. Since MDA could be easily diffused into PBS buffer, the chemical shift at 6.45 and 6.80 could be assigned to the protons ortho and meta to the amine remaining in the polymer bulk.29 The signals of terminal aromatic amine were also observed for PDMS5%-PCU and PDMS30%-PCU, indicating that PDMS failed to prevent the cleavage of urethane linkage. All the aged samples presented a new peak at 3.64 ppm corresponding to the protons next to hydroxyl groups, which resulted from urethane hydrolysis or the breakdown of carbonate linkage. To validate the hydrolysis mechanism of PDMS modified PCU, 1H NMR spectra of the corresponding hydrolysis products of the polymers in PBS were recorded. As shown in Figure S3, MDA and 1,6-hexanediol (HDO) liberated by urethane and polycarbonate carbonyls were detected. The signal of HDO was much stronger than that of MDA, indicating that the chain cleavage of soft segment proceeded faster than that of hard segment. Unfortunately, due to the interference of solvent signals (H2O, DMSO, DMAc) and the existence of multiple hydrolysis products or impurities, those peaks were hard to be clearly identified and quantified (Figure S4).


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a

b

c

d

e

H N

O O

a

d b

NH2

c d

a

b

c

e O

OH

Figure 5 1H spectra of polyurethane samples exposed to PBS for 28 d.

The relative molecular weights before and after PBS treatment were monitored by GPC (Table S1). In figure 6 where percentage of molar mass (Mn) loss was presented, PCU showed severe molar mass reduction up to 48% after 28 d of aging in PBS and PDMS5%-PCU also underwent dramatic chain scission. As the fraction of PDMS in the soft segment further increased, the hydrolysis of main chain was suppressed obviously when compared with PCU. PDMS10%-PCU, PDMS20%-PCU and PDMS30%-PCU had comparable loss of Mn (~27-30%) after immersing in boiling PBS buffer for 28 d.


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Figure 6 percentage reduction of relative molar mass (Mn) loss of PCU and PDMS-PCU aged in PBS for 14 d and 28 d.

The surface morphology of samples hydrolyzed for 28 d are shown in Figure 7. Due to the loss of low molecular weight product resulted from chain scission, the hydrolyzed PCU samples displayed micro holes compared to un-hydrolyzed ones. The holes were also observed in the PCU film incorporating 5% of PDMS in soft segment. By contrast, PCU films with higher PDMS contents exhibit smooth surface without any obvious defects.


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PCU

PCU-28

PDMS5%-PCU

PDMS5%-PCU-28

PDMS10%-PCU

PDMS10%-PCU-28

PDMS20%-PCU

PDMS20%-PCU-28

PDMS30%-PCU

PDMS30%-PCU-28


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Figure 7 SEM images of control PCU and PDMS-PCU hydrolyzed for 28 d in PBS.

To further characterize the surface properties, the WCA results are shown in Figure 8. WCA of PCU decreased dramatically from 86.7° to 57.6° after 28 d of hydrolysis, possibly due to the polar groups generated by the chain scission of backbone chain. For PDMS5%-PCU, WCA also decreased from 113.4° to 102.2°. When more PDMS were incorporated into PCU, WCA kept almost constant after degradation, confirming that enriched PDMS surfaces were attached with strong hydrophobicity and decreased hydrolysis of backbone chains generated less polar groups on the surface.

Figure 8 WCA results of PCU and PDMS-PCU tested after 0, 1, 3 and 4 weeks of aging.

The influence of hydrolytic degratdation on untimate tensile strength (UTS) is presented in Figure 9.

Obviously, UTS of PDMS-PCU decreased as more soft PDMS segments were

incorporated. UTS of PCU kept almost constant and the elongation at break were reduced (As seen in stress-strain curves in supporting information Figure S5 and Table S2). Treated PCU


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films have been observed with brittle, plastic and cross-linked surfaces.40 The possible crosslinking reactions and higher degree of phase separation led to enhanced stiffness. PDMS5%PCU displayed more rapid decrease of UTS than PCU, indicating a faster hydrolysis process. With higher content of PDMS incorporation, UTS remain nearly unchanged and the ultimate elongation increased after hydrolysis.

Figure 9 Ultimate tensile strength of PCU and PDMS-PCU after 0, 1,2, 3 and 4 weeks of aging

Degradation mechanism PDMS based polyurethanes, especially for PDMS-PEU, obtained enhanced oxidative stability due to the shielding of PDMS backbone (see Figure 10). To produce the best combination of mechanical performance and biostability, approximately 35 wt% and 50 wt% of PDMS have been mixed with PTMO and PHMO, respectively.

28, 38, 41

Here in the macrophages

mediated oxidation test, the partial substitution of PDMS for PHMC also contributed to reduced oxidative degradation.

PDMS10%-PCU incorporated only ca 12 wt% of PDMS displayed

desirable anti-oxidation property. At higher PDMS fractions, tiny holes were observed in SEM


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images. The minimal molecular weight loss ruled out the possibility of chain scission through the cleavage of backbone. In control PCU, polycarbonate carbonyls tended to form strong hydrogen bonding with N-H groups in the urethane bonds, thus enhancing hard/soft-segment miscibility and interfacial interactions. Whereas hydrophobic PDMS segment resulted in a greater degree of segment separation, arising from the immiscibility between PDMS and hard segment.20, 42 The demixing kinetics led to dramatic phase separation during solvent casting process with the generation of residual stress as well as physical defects (e.g. free volume). Therefore, the observed holes were probably caused by the physical defects instead of chemical chain scission. These results suggested that a higher fraction of PDMS mixed in macrodiols might not be desirable to improve the oxidation resistance of PDMS based PCU due to the mechanical or physical failure caused by easy phase separation, especially in solution cast process.

Figure 10 Schematic illustration of the mechanism of enhanced oxidation and hydrolysis of PDSM-PCU


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The enhanced hydrolytic stability of PDMS modified PCU was proved by GPC and SEM. Tang et al pointed out that 60% of chain scission sites were associated with the carbonate groups and the left 40% was due to the cleavage of urethane linkages.43 Herein, although the hydrolysis products were not isolated and quantified, the percentage of urethane and polycarbonate hydrolysis were estimated according to 1H NMR spectra of the samples before and after aging (supporting information), and the results were listed in Table 3. It was found that the three samples displayed similar urethane hydrolysis rates and the carbonate linkage underwent greater chain scission. The percentage of urethane hydrolysis was speculated to decrease since the materials became more hydrophobic and less susceptible non-hydrogen bonded urethane groups were presented. However, PDMS hindered the formation of hydrogen bonding between urethane amide and carbonate carbonyls. The free bonded urethane linkages (presented in MDI-PHMC and MDI-PDMS) were more vulnerable to water, which might offset the benefit brought by PDMS. Therefore, PDMS modified PCU displayed nearly the same urethane hydrolysis rate compared with controlled PCU. After incorporation of 5% PDMS, the percentage of carbonated hydrolysis increased from 2.5% to 3.25% compared with control PCU. The result is in accordance with the percentage of molecular weight reduction. Incorporation of 5% PDMS accelerated the demixing of hard and soft segments and the promoted phase segregation resulted in more polycarbonate groups exposed on the surface. Since a small amount of PDMS failed to form protective layers, the soft segments were more liable to be hydrolyzed. As the fraction of PDMS increased to 30%, the percentage of carbonate hydrolysis decreased to 1.97%. The enhanced carbonate hydrolytic stability of PCU with higher PDMS fractions can be ascribed to the following two reasons. Firstly, the hydrophobic PDMS can form a protective layer which protected the carbonate


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carbonyls in non-hydrogen bonded PHMC soft segment from being attacked by water. Secondly, hydrogen bonding plays an important role in hydrolytic chain cleavage. We previously calculated the percentage of free and hydrogen bonded carbonyl groups in PDMS based PCU36. The content of free urethane carbonyls decreased and that of hydrogen bonded ones increased as more PDMS segment were introduced, resulting in higher organized hard segment domains that can potentially mask the cleavage sites of carbonate linkages enhance their hydrolytic resistance (see Figure 10). As the molar ratio of PDMS further increased from 10% to 30%, the hydrolytic stability displayed less impressive improvement from the GPC result. As mentioned above, the demixing of hard and soft segment proceeded dramatically as more immiscible PDMS segment were present. The phase-separated microdomains contains more free volume and provided easier access for water penetration. Thus, for PDMS20%-PCU and PDMS30%-PCU, such negative effect might offset the benefit of hydrolytic stability brought by hydrophobic and stable PDMS. Table 3 Percentage of urethane and carbonate hydrolysis Urethane hydrolysis

Carbonate hydrolysis

PCU

0.92%

2.51%

PDMS5%-PCU

0.96%

3.25%

PDMS30%-PCU

0.99%

1.97%

Considering the results of oxidation and hydrolysis test, PDMS10%-PCU displayed best outcomes in terms of mechanical performance and biostability. PCU has been proved to be more oxidatively stable than PEU and even PDMS end capped PEU. PDMS-PCU displayed slower chain scission rate than PDMS-PEU.24 Here, PDMS10%-PCU with small amount of PDMS obviously enhance the oxidative stability. The hydrolysis data were compared with those obtained with commercial PEU (Elast-Eon 2A) of nearly 50 wt% of PDMS addition. Using the


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Biomacromolecules

similar solution casting film and hydrolysis conditions, Elast-Eon 2A displayed 40% of molecular loss and 30% of UTS loss after 4 weeks aging at 85 °C.31 PDMS10%-PCU showed reduced molecular weight loss of 27% and the UTS nearly kept constant about 34 MPa after 4 weeks aging at 100 °C, which was tremendously higher than the UTS of Elast-Eon 2A.

Conclusion The surface properties and biostability of silicone-modified PCU were characterized in this study. It was found that PDMS tend to accumulate on the surface layers and protect the bulk from the attack of degradative species. The oxidative resistance was thus obviously enhanced based on GPC results. At higher PDMS fractions, the demixing of PDMS soft segment and hard segment results in possible residual stress, weak interfacial interactions and undesirable visual defects. Enhanced hydrolytic resistance of PDMS-PCU was ascribed to the depressed chain cleavage of polycarbonate carbonyls by PDMS surface layer. The optimal molar ratio of PHMC/PDMS was 90:10, which realized the simultaneous improvement of oxidation and hydrolysis resistance while kept proper mechanical performance. The material would find potential use in long-term implantation applications.

ASSOCIATED CONTENT Supporting Information. SEM images of cell-treated PDMS-PCU;1H NMR spectrum of PDMS30%-PCU;1H NMR of the aqueous phase of PCU, PDMS5%-PCU and PDMS30%-PCU; Stress–strain curves of PDMS-PCU and the mechanical results; Molecular weights and molecular weight distribution of PDM-PCU before and after aging; Process for calculating hydrolysis percentage. AUTHOR INFORMATION


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*Corresponding authors. Fax: 0086-28-85405402, Email: [email protected] [email protected]. ACKNOWLEDGMENT This work was supported by the National Natural Science Foundation of China (51703139) and the National Science Fund for Distinguished Young Scholars of China (51425305).

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For Table of Contents Use Only Simultaneous

improvement

of

oxidative

and

hydrolytic resistance of polycarbonate urethanes based on polydimethylsiloxane/ poly(hexamethylene carbonate) mixed macrodiols Zhen Li, Jian Yang, Heng Ye, Mingming Ding, Feng Luo, Jianshu Li, Jiehua Li*, Hong Tan* and Qiang Fu


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Simultaneous improvement of oxidative and hydrolytic resistance of

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