Self-Defensive Antimicrobial Shape Memory Polyurethanes with Honey-Based Compounds

Infection treatment plays a crucial role in aiding the body in wound healing. To that end, we developed a library of antimicrobial polymers based on segmented shape memory polyurethanes with nondrug-based antimicrobials (i.e., honey-based phenolic acids (PAs)) using both chemical and physical incorporation approaches. The antimicrobial shape memory polymers (SMPs) have high transition temperatures (>55 °C) to enable maintenance of temporary, programmed shapes in physiological conditions unless a specific external stimulus is present. Polymers showed tunable mechanical and shape memory properties by changing the ratio, chemistry, and incorporation method of PAs. Cytocompatible (∼100% cell viability) synthesized polymers inhibited growth rates of Staphylococcus aureus (∼100% with physically incorporated PAs and >80% with chemically incorporated PAs) and Escherichia coli (∼100% for samples with cinnamic acid (physical and chemical)). Crystal violet assays showed that all formulations inhibit biofilm formation in surrounding solutions, and chemically incorporated samples showed surface antibiofilm properties with S. aureus. Molecular dynamics simulations confirm that PAs have higher levels of interactions with S. aureus cell membranes than E. coli. Long-term antimicrobial properties were measured after storage of the sample in aqueous conditions; the polymers retained their antimicrobial properties against E. coli after up to 20 days. As a proof of concept, magnetic particles were incorporated into the polymer to trigger user-defined shape recovery by applying an external magnetic field. Shape recovery disrupted preformed S. aureus biofilms on polymer surfaces. This antimicrobial biomaterial platform could enable user- or environmentally controlled shape change and/or antimicrobial release to enhance infection treatment efforts.

1. Chemical characterization of glycerol modification with phenolic acids.Figure S1 shows 1 Hnuclear magnetic resonance spectra of modified cinnamic (left) and p-coumaric (right) acids.The introduction of a shift at ~4.4-4.5 (B) after glycerol esterification was used to confirm successful synthesis with ~92% modification of glycerol with phenolic acids (standardized to ring shifts at ~7.4-7.5).

Figure S1.
Nuclear magnetic resonance spectra of glycerol modified with cinnamic (left) and p-coumaric (right) acids.
2. Atomistic to CG mapping scheme.Figure S2 shows the MARTINI coarse grain models for CA: Cinnamic acid, PCA: p-coumaric acid, and FA: ferulic acid.Table S1 specifies that MARTINI force field parameters for CA, PCA, and FA.S3 shows the FTIR results of polyurethanes with incorporated phenolic acids: CA: Cinnamic acid, PCA: p-coumaric acid, MPCA: modified PCA, FA: ferulic acid.4. Thermal analysis of polyurethanes. Figure S4 shows the differential scanning calorimetry thermograms used to determine glass transition temperatures (Tg) and melting temperatures (Tm) of the hard segments of synthesized polymers.5. Mechanical analysis of polyurethanes. Figure S5 shows stress vs. strain curves obtained from tensile testing of synthesized polymers, which were used to calculate tensile strength, elongation at break, and modulus.6. Shape memory properties of polyurethanes. Figure S6 shows dynamic mechanical analysis plots obtained during shape memory testing of synthesized polymers, which were used to calculate shape fixity and shape recovery.

Figure S6
. Dynamic mechanical analysis of shape memory properties of synthesized polymers over 3 cycles.
7. Thermomechanical, shape memory, and degradation properties of polyurethanes with direct chemical incorporation of unmodified CA and PCA.Table S2 shows that chemical incorporation of unmodified CA and PCA into the polyurethane resulted in weak and brittle polymers.In the case of CA, failure occurred during sample cutting with a dog bone punch, preventing mechanical characterization.This brittleness is attributed to termination of the polymer chains by CA and PCA, which only have one functional carboxylic acid group, that likely results in short chain polymers or oligomers during synthesis.In the case of PU-PCA-4%, we were able to obtain dog bone samples and run tensile testing.This effect may be due to the OH pendant group on PCA, which could aid in physical crosslinking.However, low elongation and tensile strength still show the relative brittleness of these polymers.PU-CA-4% and PU-PCA-4% (unmodified CA and PCA) do not exhibit shape memory properties due to these effects.

Figure S2 .
Figure S2.(a) The atomistic structures and (b) CG models of CA, PCA, and FA.The CG bead types P1, SC5, SC4, SP1, and Na are labeled in magenta, green, orange, cyan, and red, respectively.

Figure S3 .
Figure S3.FTIR spectra of polyurethanes with a) chemical incorporation of unmodified CA and PCA, b) chemical incorporation of modified PCA, c) physical incorporation of PCA, and d) physical incorporation of FA.

Figure S5 .
Figure S5.Stress vs. strain curves of synthesized polymers with (a) chemically incorporated and (b) physically incorporated phenolic acids.
Figure S7 (lower) shows FTIR and corresponding hard segment Tg of samples with chemically incorporated unmodified CA and PCA throughout 10 days of storage in PBS at 37°C.Surface chemistry and thermal properties remained stable in these polymers during this time frame.

Figure
Figure S7.(Upper) Mass loss of polyurethanes (PU) with chemically incorporated unmodified PAs compared to control.(Lower) FTIR and corresponding T g (N=1) of control polyurethane and samples with chemically incorporated unmodified PAs throughout 10 days of storage in PBS at 37°C.

Table S1 .
MARTINI force field parameters of CA, PCA, and FA.

Table S2 .
Thermo-mechanical properties of synthesized PUs with chemically incorporated PAs.Mean ± standard deviation displayed.N = 1 for R f and R r ; N = 3 for mechanical, and thermal properties.
As shown in FigureS7(upper), chemical incorporation of unmodified CA increases mass loss compared to polyurethanes with modified CA, which is attributed to brittleness of the polymer structure.On the other hand, chemical incorporation of unmodified and modified PCA resulted in reduced mass loss due to stronger interactions between PCA and polymer chains.