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Open Access Original Research
Mesoporous Silica Nanoparticles to Tune Oxidative Degradation Rates in Composite Shape Memory Polymers

Andrew Weems 1, *, Wenyan Li 2, Duncan Maitland 1, Luz Marina Calle 2

1. Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77840 , USA

2. Corrosion Technology Laboratory, NASA, Kennedy Space Center, FL, 32899, USA

Correspondence: Andrew Weems

Academic Editor: Hossein Hosseinkhani

Special Issue: Applications and Development of Biomaterials in Medicine

Received: September 12, 2019 | Accepted: December 20, 2019 | Published: December 31, 2019

Recent Progress in Materials 2019, Volume 1, Issue 4, doi:10.21926/rpm.1904008

Recommended citation: Weems A, Li W, Maitland D, Calle LM. Mesoporous Silica Nanoparticles to Tune Oxidative Degradation Rates in Composite Shape Memory Polymers. Recent Progress in Materials 2019;1(4):16; doi:10.21926/rpm.1904008.

© 2019 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

Abstract

Biomedical applications of shape memory polymers (SMPs) are limited by their biostability, degradability, and possible toxicity risks after implantation. Mesoporous silica nanoparticles (MSNs) were used to increase the oxidative biostability (increase time until degradation occurs) using antioxidants and to induce oxidative degradation through incorporation of hydrogen peroxide-containing MSNs with modified surfaces. The presented results confirm increased oxidative stability using antioxidants, and alternatively, oxidatively degraded SMPs when using MSNs and peroxide. Thermal stability was increased by approximately 10% with the inclusion of antioxidants. With the surface modification and incorporation of hydrogen peroxide, the elastic modulus was nearly 8 times greater, indicative of oxidative degradation and the strain to failure was decreased to 20% of that of the control formulation. In phosphate buffered saline (PBS), the SMPs were found to undergo mass loss until the solid polymer degraded completely, unlike the control formulations which have been found to be hydrolytically stable for more than a year with no change in mass.

Keywords

Shape memory polymer; degradation; mesoporous silica nanoparticles; oxidation

1. Introduction

Shape memory polymers (SMPs) are a class of smart materials of great interest in biomedical applications, and can be used in applications such as tissue scaffolds or medical devices [1,2]. For many biomedical applications, such as cardiovascular aneurysm occlusion devices, a low-stress shape recovery behavior is ideal in that the material could fill a void space without causing excessive deformation or pressure on the surrounding tissue: the void would be filled without pain for the patient [3,4]. A series of thermoset polyurethanes have been processed into highly porous SMP foams using symmetric aliphatic amino alcohols and diisocyanates to achieve high-strain recovery materials for aneurysm occlusion [5]. Degradation studies of these SMPs have revealed a susceptibility to oxidative degradation, with in vitro behaviors modeled with hydrogen peroxide (H2O2) and revealing tertiary amine fragmentation [5]. These fragmentation reactions produce secondary amines and aldehydes; subsequent oxidation-reduction reactions, in the presence of H2O2, produce primary amines from secondary amines [5,6]. These studies determined that approximately 2% H2O2 was sufficient for modeling the real-time degradation rates of the SMPs in cerebrovascular aneurysm environments over an initial 90-day implantation, which also demonstrated the biocompatibility and utility of these SMPs for occluding such aneurysms [5,7]. The products produced over the life of the SMP have been indicated to be cytocompatible at the levels released during mass loss, and more importantly, work by Oliva et al. suggests that similar aldehyde functional groups could improve biomaterial-tissue adhesion, and thus this degradation may be fortuitous over the long-term, despite it being reliant upon the cellular response to the material [5,7,8]. In general however, controlling the degradation of SMPs, either by increasing the degradation rate or increasing biostability, would broaden potential medical applications [9,10,11].

Previous work with enhancing the biostability of these SMPs has indicated that butylated hydroxytoluene (BHT) and piperidine derivative (Piper) antioxidants are effective at increasing the material lifespan in oxidative environments, by preferentially reacting with hydroxyl radicals instead of the tertiary amines in the SMP matrix [11]. BHT and Piper showed limited effectiveness when directly added to the SMP matrix, due to poor retention of the BHT or to the isocyanate-Piper reactions that produce a more rigid polymer; antioxidants were found to be more effective when they were incorporated in microparticle composite SMPs, but the microparticle additives may lead to pore collapses [11]. Furthermore, attempts to enhance the degradability of these or other SMPs have been limited primarily to inclusion of poly(lactic acid) or polycaprolactones, heparin and biomolecules, or synthesis of polyester prepolymer networks that require altered foaming conditions [12,13,14,15,16,17]. A different approach that allows for easy tailoring of degradation without modification of the synthetic procedure is needed.

Hydrogen peroxide, one such degradation-inducing molecule, is of interest in a variety of applications not only because it has found use as degradation media in vitro, but also because it is produced in vivo in response to foreign bodies as well as a cellular signaling molecule. The variety of methods for modifying Si particles indicates the broad range of possible avenues for surface adsorption techniques to achieve H2O2 retention [18,19,20,21,22,23]. For example, in Rosenholm’s and Lewandowski’s approach, silylation of MSNs may be used to form surface tethering groups to retain small molecule payloads in the MSN pores [5,19,23].

Presented here is the synthesis and subsequent incorporation of mesoporous silica nanoparticles (MSNs) into SMPs as a platform for tailoring oxidative degradation; MSNs may be modified to incorporate either a biostability-enhancing payload or a degradation-inducing payload. The particle modifications are of particular interest because H2O2 may be used to selectively induce degradation of the SMPs, which has not been attempted previously. Ideally, this system would ensure that tissue could replace an implanted scaffold regardless of cellular response to the material, provided the concentration of peroxide is kept below toxic thresholds and in the local vicinity of the polymer chains to prevent side reactions. To the best of our knowledge, this is the first attempt at controlling the degradation of SMPs using peroxide-loaded MSNs.

2. Materials and Methods

2.1 General

Materials were purchased from Sigma-Aldrich and used without modification unless otherwise stated. Hexamethylene diisocyanate (98%, HDI), triethanolamine (99%, TEA), N,N,N′,N′-tetrakis (hydroxypropyl) ethylenediamine (98%, HPED), butylated hydroxytoluene (BHT), 1,2,2,6,6 tetramethyl piperidinol (Piper), (3-aminopropyl)triethoxysilane, Phloxine B (PhB) were used as monomers. Ethanol (97%, EtOH) and isopropyl alcohol (99.5%, IPA) were used as solvents for cleaning the materials after synthesis and degradation testing, respectively. Cobalt chloride (CoCl2) and H2O2 (50% wt/wt) were used for degradation analysis. Spectral data collection was performed in triplicate to confirm results. X-ray photoelectron spectroscopy (XPS) (Omicron™ XPS with Argus detector) using a Mg/Al x-ray source was used to characterize particles and SMPs. Fourier transform infrared spectroscopy (FT-IR) attenuated total reflectance (ATR) was performed using a Bruker ALPHA infrared spectrometer (Bruker, Billerica, MA); 48 scans per spectra of both background and samples were used. Spectra data were collected in absorption mode with a resolution of 4 cm-1. OPUS™ software was used to examine spectra, identify peaks, and perform baseline and atmospheric corrections. Fluorescence wavelengths were examined using a Fluoromax Fluorometer (Horiba UK Limited, Middlesex, UK). Selected excitation wavelengths were determined from the literature and confirmed by excitation scans; PhB was excited with approximately 515 nm [11,24].

2.2 Mesoporous Silica Nanoparticle (MSN) Synthesis

A modified Moller’s protocol (Moller’s procedure A) was used for particle synthesis with triethanolamine (TEA) along with cetyltrimethylammonium bromide (CTAB) as the surfactant [25]. Antioxidants BHT and Piper were substituted, stoichiometrically, for TEA for the alcohol group concentration during synthesis of degradation-resistant, antioxidant-loaded MSNs; TEA was used for producing plain MSNs.10 In short, a stock solution of DI H2O (64 mL), 10.5 mL EtOH, and 25% wt CTAB was mixed together for 20 min at room temperature. TEA (16.5 mL) was added dropwise and stirred until dissolved. To this stock solution was added 1.5 mL TEOS (dropwise over 5 min) while stirring, and continued to stir until a whitish-grey power formed over the course of 30 min. The pore template was removed following established literature protocols for washing and extraction. Specifically, particles were washed using the same protocol in a combination of acetone and water (50/50 volume), centrifuged for 30 min, washed again (twice more), and dried under vacuum at 50 °C overnight. Particle characterization was performed using transmission electron microscopy (TEM), where particle sizes and pore diameters were determined using ImageJ (Bethesda, MD) for particle analysis.

2.3 Particle Modification with (3-Aminopropyl) Triethoxysilane

Following a modified protocol by Paris for MSNs modification, (3-aminopropyl)triethoxysilane (10 g) was reacted with glycolic acid by transesterification, using 2 drops of concentrated HCl in 50 mL DCM with 10 g of MSNs suspended in toluene [26]. The suspension was refluxed for 36 h, followed by washing once with 1 M NaOH, once with 1 M HCl, and 2 washes with DI H2O [26]. The solid particles were collected by vacuum filtration and resuspended in THF (Figure S1). 1H NMR (CDCl3): 3.02 (s), 2.64-2.48 (t), 1.81-1.69 (m), 1.07-0.98 (t). 13C (CDCl3): 48.6, 29.8, 8.4.

2.4 Oxidation and Incorporation of H2O2

To the THF-particle solution was added 10 mL 50% H2O2 followed by stirring for 12 h. Particles were separated by centrifugation. Iodometric titration was used to determine peroxide concentration, indicating approximately 10% incorporation [5]. 1H NMR (CDCl3): 3.02 (s), 2.64-2.48 (t), 1.81-1.69 (m), 1.07-0.98 (t). 13C (CDCl3): 169.4, 63.4, 52.1, 48.6, 23.9, 4.1.

2.5 Loading Efficiency and Release

PhB and Nile blue chloride were incorporated into MSNs during particle synthesis, through the addition of 1% wt (of final theoretical particle mass) of selected dye in the solution. Particles were collected and washed in the same manner as described above. Release studies were performed as described for poly(urethane urea) microparticles; emission wavelength shifts were used to characterized structural changes in the dyes at neutral pH (PBS, pH = 7.4) [11,24]. The fluorescence emissions of virgin dye and dye released from MSNs at neutral pH (PBS, pH = 7.4), and high pH (1 M KOH) was used to further confirm no structural changes had occurred.

2.6 SMP Synthesis

HDI, TEA and HPED were mixed together in a ratio of 105:67:33 (NCO:OH:OH) stoichiometrically. The solution was mixed until all components were dissolved, followed by the addition of MSNs at weight percentages of 1.0, 2.5, 5.0 and 10.0% (wt of final polymer). Films were then cured at 50 ˚C for 36 hours under ambient atmosphere.

2.7 Tensile Testing

Uniaxial tensile testing was performed on ASTM d638 IV samples using an Instron Tensile Tester with 500 N load cell. The extension rate was set to 5 mm/min at room temperature and ambient conditions. Seven samples were tested for each species. Elastic modulus, strain to failure, ultimate tensile strength, and toughness were calculated as averages for each sample species.

2.8 Thermal Analysis

Thermogravimetric analysis (TGA) was used to assess any changes in thermal degradation temperatures. A TA Q50 TGA (TA Instruments, New Castle, DE) was used to heat samples to 500 °C at 10 °C/min under a mixed atmosphere of oxygen and nitrogen (60 mL/min to 40 mL/min respectively). Samples were examined for the onset of degradation temperature and major transitions in the mass loss profiles.

2.9 Shape Recovery

For shape memory testing, films were cut into bars (5 mm by 25 mm by 1 mm) and bent until both ends touched (100% strain) after isothermal incubation for 5 minutes at 50 °C. The film deformation was mechanically held as the film cooled to room temperature, at which point the film was released. Strain fixation (change in strain at room temperature) as well as strain recovery extent (change in strain at 37 °C) were examined immediately upon release. Strain measurements were taken optically at 1-minute increments over 6 minutes, and then 5-minute increments out to 30 minutes. Strain recoveries were calculated as the change in angle from the deformed film.

2.10 Gravimetric Analysis

Structural changes to the MSNs’ payloads were performed using the same release experiment described in Section 2.5. In short, fluorescent-dye containing MSNs were incorporated into films in the same manner as for other payload-containing MSNs. After curing, films were immersed in 37 °C PBS, and released dye was characterized in the same manner as previously described [24]. For analysis of degradation rates, cleaned samples were completely immersed in respective solutions of 3% H2O2 (real time oxidation) and 20% H2O2 with 0.1 M CoCl2 (accelerated oxidation), both stored at 37 ˚C, based upon previously published procedures [5]. A second series of samples was immersed in phosphate buffered saline (PBS, pH = 7.4) which was refreshed weekly. Samples were held isothermally at 37 °C for the duration of the study in a static chamber and removed only for gravimetric analysis. During analysis, samples were rinsed with acetone, followed by DI water and then blotted dry before being weighed. Sample weights were recorded and averaged for each time point (n = 7).

3. Results and Discussion

3.1 MSN Synthesis and Characterization

MSN formation was confirmed using transmission electron microscopy (TEM) (Figure 1), which showed all MSN species to be spherical particles possessing pores of approximately 4 nm in diameter and a diameter of 87 ± 11 nm, similar to previously reported results (Figure S2) [27]. Unmodified MSNs (controls) exhibited a pore morphology of 4 nm pores with a diameter of diameter of 43 ± 12 nm, similar to previous reports of such particles [17,25]. The pore size was consistent across the three conditions of MSN synthesis, even though the particle species possess statistically differing diameters, and the pore morphologies may vary; the specific mechanism of this behavior is currently unknown. MSNs synthesized in the presence of BHT or Piper displayed similar pore morphology as the controls (diameter of 43 ± 12 nm, pores of 4 nm). However, the morphology of the MSNs synthesized using Piper could be altered to produce worm-like pores (diameter 67 ± 14 nm, pores of 4 nm). 12-13 Further examination also revealed that the particles may aggregate into sheets, although this primarily seemed to occur for BHT-containing or plain MSNs particles. Ultimately, this confirmed the porous particle structure demonstrated by Möller and others for similar synthetic works was produced, and thus was not further characterized [17,25].

Figure 1 (a) Transmission electron microscopy (TEM) representative images displaying MSNs produced with no antioxidant, (b) BHT and (c) Piper.

In order to determine antioxidant retention and interactions with particles and films, the fluorescent dye PhB was incorporated in the same manner as the antioxidants into MSNs. However, the majority of the dye seemingly is not reacted and remains as small molecules in the pores of the particles, as demonstrated by the lack of change in the emission or excitation wavelengths of the PhB in the MSNs (Figure S3), similar to behavior found when using polyurethane microparticles compared to small molecule PhB in the SMP foams [11,24]. This emission spectra change indicates that the small molecules are accumulating in the MSN pores, rather than on the particle surface, and will therefore retain their functionality after polyurethane network formation, rather than being incorporated into the SMP backbone [17]. FT-IR analysis of the MSNs particles (Figure S4) follows previously published spectra of similar particles, further indicating the presence of silica surfaces with antioxidants present in the particle pores.

Spectroscopic analysis of the MSNs using XPS revealed that the BHT antioxidant was less prevalent on the surface compared to the Piper (Figure S5). Plain particles had approximately 27% silicon on the surface, while BHT and Piper had 16.7 and 11.3 % respectively, indicating that the antioxidants are partially present on the particle surface. This is supported by the increase in the surface carbon content. Residual nitrogen may be attributable to the TEA, as well as the nitrogen in the Piper ring. Interestingly, the surface oxygen concentration decreased, presumably due to the antioxidants and residual surfactant covering the oxygen on the particle surface.

With the surface-modified particles, the growth of the surface graft was tracked through the change in the surface silicon, carbon, and oxygen content using XPS (Figure 2, Table S1). As mentioned previously, the silicon concentration was reduced with surface modification, with each subsequent reaction step decreasing from nearly 27% to 6.1% with the final modification. The surface oxygen decreased from 30.8% in the plain particles to 28.5% but then increased, as additional reactions increased the available alcohol groups associated with the glycolic acid. Carbon content dramatically increased with the addition of the silyl tether and glyoxal, both of which greatly increase the surface carbon content, but with the peroxide it decreased from 59.1% to 54.3%. Finally, the surface tether was found to increase nitrogen content 400%, before decreasing 33%, indicating that a large number of amine groups are consumed to form amide bonds. However, the addition of the peroxide may cleave some amide bonds, as indicated by the increase in the nitrogen content on the surface after the final modification. The N1s spectra further indicated formation of nitroso and nitro groups, in addition to the amide and amine functional groups, possibly due to amide cleavage and subsequent oxidation to nitro and nitroso of the amine.

Figure 2 XPS analysis of surface modified particles displaying the relative concentration of Si (a) and N (b), along with the Si2 peak scan (c), C1s peak (d), N1s scan (e), and O1s (f) of MSNs. (g) Schematic displaying MSNs with surface modifications to produce an amine functionalized surface, an alcohol functionalized surface, and a carboxylic acid functionalized surface with hydrogen peroxide contained within the particle pores.

3.2 SMP Film Characterization

After the particle morphology and size was confirmed, the composite SMP films were characterized. FT-IR analysis found the carbonyl shoulder centered at 1704 cm-1, indicative of both a urethane linkage as well as a high degree of hydrogen bonding; this is higher than previously reported spectra of these materials, possibly due to interactions between the MSN surfaces and isocyanates, although previous studies have utilized isocyanate functionalized MSNs without side reactions, indicating this is unlikely [5,15]. A second possibility is a change in the hydrogen bonding of these materials compared with previous examinations. Unlike previous syntheses of these SMPs, a sharp, dominant peak is displayed at 1624 cm-1, indicating a higher degree of urea linkages present, supported by a similarly dominant peak at 1551 cm-1 [5,15]. This distinct shoulder at 1458 cm-1 may correspond to the peak at 1445 cm-1 displayed in the MSN FTIR spectra, indicating the particle presence in the films. Greater analysis of the these SMPs and the characteristic FTIR peaks are discussed elsewhere [5,10,11,15,16,24]. Importantly, use of antioxidants in the particles did not significantly alter the spectroscopic signal from the SMPs, indicating that the antioxidants may be accumulated within the pores rather than on the particle surface and is therefore not interacting significantly with the material matrix during polyurethane synthesis. This is further supported by TGA of the particles, which revealed that BHT MSNs could be used to extend the thermal stability of the SMPs from approximately 223 ˚C (control SMPs and Piper MSNs composite SMPs) to 271 ˚C for BHT MSNs, similar to results found using polyurethane microparticles in porous SMPs [11]. With the incorporation of the MSNs into films, the functionality of the payload was again examined using the same fluorescent dye technique. This is because during film synthesis, PhB may react with nearby isocyanate groups during SMP synthesis in a similar manner as the Piper antioxidant, producing carbamate linkages and resulting in slight red shifts in the fluorescence emission spectra; microparticles were shown to be an effective way for reducing both this reaction and the subsequent red shift and this same behavior was used for MSN-composite films [11,24].

3.3 SMP Film Mechanical and Shape Recovery Analysis

Tensile examination of the composite SMPs indicated that the MSNs, at approximately 2.5 wt% loading, increase the elastic moduli, ultimate strength and toughness without statistically altering the strain to failure (Figure 3, Figure 4). At higher loadings, as expected, the particles result in increased strain to failure, up to nearly 250% due to disruptions of the matrix material by such high volumes of particles and possible residual plasticizing agents such as the CTAB. With the antioxidant-containing MSNs, a similar trend was found for up to 2.5 wt% of particles. However, at higher concentrations, the strain to failure was not significantly increased compared to the controls. Unlike BHT, Piper did not cause increased moduli at low concentrations and otherwise presented lower ultimate strengths and toughness, but with increasing particle concentrations did have better strains to failure compared to BHT.

Modification of the particle surface was used as a possible method for increasing the rate of SMP degradation. Interestingly, at 10% particles (and thereby peroxide concentration of approximately 10%), the elastic modulus and ultimate strength of the SMPs was found to be significant relative to that of the other materials, and strain to failure was dramatically reduced (Figure 5). This corresponds to the behavior found previously when examining the oxidative behavior of the SMPs in both accelerated and real time equivalent in vitro testing [11]. However, the behaviors here were found to occur after the brief annealing post-synthesis, indicating that the peroxide-containing MSNs can degrade SMPs.

Figure 3 Representative stress-strain curves for unmodified MSN-composite SMP films, tested at ambient conditions, 5 mm/min strain rate, ASTM Type IV dogbones.

Figure 4 Elastic moduli and ultimate strength (a), and strain to failure and toughness (b) as functions of weight loading percentages of unmodified MSNs in SMP composite films (Tested at ambient conditions, 5 mm/min strain rate, ASTM Type IV dogbones, n = 7).

Shape recovery behavior (Figure 6) was analyzed using films bent 180° with recoverable strains calculated by the angle of recovery over time. The strain recovery behavior followed the mechanical analysis, as the materials possessing high elastic moduli (and lower toughness) displaying reduced recoveries. In the H2O2-containing SMPs, films achieved a maximum recoverable strain of ca 65% even after 30 minutes. This loss of strain recovery is most likely due to a complex series of mechanisms, including scission of the polymer network due to oxidation, fracture of the film due to decreased toughness, and possible side reactions in the presence of the peroxides. However, this loss of recoverable strain is partially offset by the increase in net point formation due to residual surface groups, such as amines or carboxylic acids, which may form covalent crosslinks during SMP synthesis.

Figure 5 The elastic moduli of the SMPs as a function of MSNs concentration (with varied surfaces) tested at ambient conditions 2 weeks after synthesis (a), the strain to failure (b), ultimate tensile strength (c), and toughness (d) conducted at ambient conditions, 5 mm/min strain rate, ASTM Type IV dogbones. (n = 7).

Figure 6 Representative shape recovery profiles, displaying the recovered strains over time, comparing the concentration of unmodified MSNs in SMP films (a) and with 10% MSNs of different additive species (b).

3.4 Gravimetric Analysis

Gravimetric studies (Figure 7) conducted in PBS at 37 °C over the course of 3 months, revealed tailorable degradation rates are achieved using MSNs for composite SMPs. In accelerated oxidative conditions, the inclusion of 10 wt% MSNs containing antioxidants was revealed in increase the biostability of the SMPs in a similar manner to that found with polyurethane microparticle additives [11]. Lower concentrations were not found to be effective, and the inclusion of H2O2 functionalized particles did not accelerated degradation significantly, either. This is attributed to the relative concentration of hydroxyl radicals produced in the accelerated solution compared with those produced during heterolytic scission of the peroxide due to temperature, which is found to be negligible over a 24 h period, which would influence the degradation rate [28,29].

Figure 7 Gravimetric analysis of SMPs comparing the different additives (10% wt MSNs) in accelerated oxidative conditions (a), and different concentrations of H2O2-containing MSNs in PBS compared with bare and antioxidant-loaded MSNs (b); samples were examined statically at 37 ˚C. (n = 7).

In neutral PBS, the control materials, antioxidant-containing MSN-composite SMPs, and low concentrations of MSNs did not display decreased mass over the course of the study. However, 10% MSNs was found to cause significant mass loss relative to the other concentrations and the control SMPs, eventually leading to fracturing of the composite SMP; an important note of this study is that the degradation solution was comprised of only PBS. It is interesting to find that sufficient peroxide is retained within the composite SMP for degradation to begin occurring within 20 days of the initial time point. Within the first 50 days of incubation in PBS, all samples are statistically similar with regards to mass change, although a trend begins to emerge within the first 30 days. By 60 days, the 10% MSNs-composite SMPs containing H2O2 display a statistically different mass compared with the lower concentrations with a mass loss rate of nearly 0.5% loss per day (compared with the 5% MSN-composite SMPs which displayed approximately 0.2% mass loss per day and negligible mass loss for the other formulations), and after ca 90 days, the same materials are fragmented into small fragments. This behavior also provides an additional measure for biomaterial integration and degradation when used as an implant: despite ca 50% mass remaining, the SMP will fragment (Scheme 1). This fragmentation will produce porosity in the implant, allowing for more rapid tissue infiltration and ultimately, healing of the implant site [7]. A second important note on this behavior is that while oxidation and mass loss are found in this case, the fracturing of the final material does not indicate complete erosion of the material. Rather, the peroxide present in the material, and possibly SMP matrix disruptions due to particle presence, result in sufficient degradation for material swelling to also begin. This swelling occurs due to the presence of carboxylic acid chain ends throughout the SMP matrix, rather than only at the surface as displayed during surface eroding oxidative degradation in the SMP foams presented previously [5,10,16].

Scheme 1 H2O2 (red marks) in the MSN (left, not to scale) released in the in the presence of the polyurethane network (center) result in oxidation of the amines to produce amine oxides, secondary amines, primary amines, aldehydes, and carboxylic acids (right).

As determined previously, rapid degradation in porous materials used for aneurysm occlusion should take place over time periods greater than 30 days, in order to allow for healing, such as endothelialization and initial collagen deposition [5,30,31]. While further tuning is needed for these materials to be translated towards the clinic, the initiation of oxidative degradation without requiring a specific cellular response or external stimuli is promising for remodeling tissue without compromising the mechanical integrity of the tissue during healing. Further work is needed, however, to achieve low density scaffolds incorporating this method. Additional work is needed to optimize the mechanical behavior of the system. While many biological systems would be appropriately served by such soft materials (regardless of the loading concentration of MSNs), the reduction in mechanical performance with 10% loading of MSNs may limit the material utility in applications requiring high-strain elastomers such as pacemaker wire lead coatings. However, most tissue engineering applications are not expected to be impacted by the slight reduction in strain-at-break demonstrated here.

4. Conclusions

In conclusion, we utilized MSNs as a platform for tailoring oxidative degradability of SMPs through the incorporation of either antioxidants or H2O2. The use of the H2O2-containing SMPs was found to be useful for inducing oxidative degradation in a hydrolytic environment, as well as resulting in mechanical property migration with increased concentration of H2O2, and to our knowledge, it is the first instance of MSNs used to induce degradation in SMPs. We demonstrate the basic usefulness of this method for tuning degradation rates as a function of particle loading, allowing for rapid selection of oxidation rate regardless of the environment into which the material is introduced, and we anticipate that this tunable degradation behavior could be of great interest in expanding the utility of cardiovascular-slated SMPs. Further work will focus on selective release or gate-keeping functionalities for additional control of payload release, to provide even greater control of the material stability.

Acknowledgments

We would like to acknowledge the NASA Harriett G. Jenkins Fellowship (NNX15AU29H, A. C. W.). We also thank Alexandra Easley for review of the manuscript.

Author Contributions

These authors contributed equally to this work.

Competing Interests

Regarding conflicts, Andrew C Weems holds stock in Shape Memory Medical, Inc. (SMM), which holds a license for the shape memory polymers developed in Maitland’s laboratory. Duncan Maitland owns stock and is on the board of directors at SMM.

Supporting Information

The Supporting Information, including experimental methods, spectroscopic analysis, statistical analysis, additional TEM images, and thermogravimetric analysis, is available free of charge on the ACS Publications website at DOI.

Additional Materials

1. Figure S1. 13C NMR spectra of MSNs modified with amide functionalization (a) and subsequent oxidation with the introduction of hydrogen peroxide (carbonyl region, b) (CDCl3).

2. Figure S2. Particle size and particle pore distributions (a) along with aggregation images of control particles (b- d). Statistical analysis (t-test, 0.05 confidence) was used to determine statistical difference between pore diameters and particle diameters, with no differences found between pore diameters (red bar).

3. Figure S3. Fluorometry of MSNs containing phloxine B, composite SMP-MSN materials, and released phloxine B small molecules from the composite SMP-MSN.

4. Figure S4. FTIR of SMP composites and control MSNs (a) along with TGA thermograms (b).

5. Figure S5. XPS survey scan (a), C1s (b), N1s (c) and O1s (d) of MSNs controls, and those containing Piper and BHT antioxidants, respectively.

6. Table S1. Atomic compositions of MSNs containing antioxidants or surface modified for incorporation of H2O2.

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