Bacterial protease‐responsive shape memory polymers for infection surveillance and biofilm inhibition in chronic wounds

Abstract

Chronic wound healing is often negatively impacted by infection. Efficient infection assessment is crucial for effective treatment, and biofilm inhibition could improve treatment efficacy. To that end, we developed a bacterial protease‐responsive shape memory polymer based on a segmented polyurethane with incorporated poly(glutamic acid) peptide (PU‐Pep). Poly(glutamic acid) degrades in response to bacterial proteases to trigger shape recovery of PU‐Pep films that are programmed into a secondary shape. These materials have transition temperatures well above body temperature (~60°C), which enables stable storage in temporary shapes after implantation. Synthesized polymers have high shape fixity (~74%–88%), shape recovery (~93%–95%), and cytocompatibility (~100%). Strained PU‐Pep samples underwent shape recovery within ≤24 h in response to the V8 enzyme from Staphylococcus aureus (S. aureus, ~50% recovery) and multiple bacteria strains (S. aureus [~40%], Staphylococcus epidermidis [~30%], and Escherichia coli [~25%]), and they had minimal shape change in response to media controls and mammalian cells. Shape recovery of strained PU‐Pep samples prevented biofilm formation on the sample surfaces, and resulting attached planktonic bacteria were vulnerable to applied treatments. PU‐Pep with physically incorporated antimicrobials simultaneously prevented biofilm formation and killed isolated bacteria. PU‐Pep dressings displayed visible shape change and resistance to biofilm formation in in vitro and ex vivo models. In the in vitro model, PU‐Pep shape change also disrupted pre‐formed biofilm structures. This novel bacterial protease‐responsive biomaterial could serve as a wound dressing that changes shape specifically during bacterial colonization to alert clinicians to infection and make biofilm‐associated infections easier to treat.

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

“…As PA content increases in polymer films, surface roughness qualitatively increases, particularly in physically incorporated samples with higher (i.e., 12%) PA concentrations, which show similar crystal-like morphology to the PA powders. Control PU samples after exposure to bacteria (Figure b) have a thick layer of biofilms after 24 and 48 h, as shown by us previously, while only planktonic bacteria are visible on Ag foam surfaces (Figure c).…”

“…To explore the value of the shape memory properties with this system, we performed a biofilm assay following magnetic field actuation of magnetically responsive SMPs, as shown in Figure a. This study was based on previous research showing that shape change of SMPs can disrupt and/or prevent biofilm formation. ,, In this proof-of-concept experiment, we incorporated magnetic nanoparticles into PU-CA-8%, which has robust biofilm formation (Figure d). Application of an alternating magnetic field causes vibration of the nanoparticles within the polymer and generates localized heating to trigger shape change in strained samples. , Visible recovery (∼46%) of nanoparticle-containing PU-CA-8% was observed after magnetic field application, as shown in Figure b.…”

“…As PA content increases in polymer films, surface roughness qualitatively increases, particularly in physically incorporated samples with higher (i.e., 12%) PA concentrations, which show similar crystal-like morphology to the PA powders. Control PU samples after exposure to bacteria (Figure 7b) have a thick layer of biofilms after 24 and 48 h, as shown by us previously, 29 while only planktonic bacteria are visible on Ag foam surfaces (Figure 7c). After chemical incorporation of modified PAs, 4% MCA and 4 and 8% MPCA samples had visible biofilm coverage by 24 h; however, antibiofilm properties are observed at 48 h on these three sample types, indicating that biofilms formed in the first 24 h were broken down between 24 and 48 h. Additionally, biofilm inhibition was observed at both 24 and 48 h for higher concentrations (12%) of MPCA (Figure 7d).…”

“…Our previously developed polyurethanes with high transition temperatures could provide a reliable platform for wound healing applications that can be coupled with safe antimicrobial agents and specific responsive moieties, including magnetic particles, light-responsive particles, peptides, or pH- and ROS-responsive agents . We previously demonstrated magnetic and bacterial-protease response in these SMPs to enable user or environmental control over shape change. ,, …”

“…28 We previously demonstrated magnetic and bacterial-protease response in these SMPs to enable user or environmental control over shape change. 25,28,29 To make antimicrobial wound dressing materials, we took advantage of phenolic acids (PAs). PAs are honey-based nondrug agents with proven antimicrobial properties against a range of bacterial strains; they effectively change bacterial membrane permeability and/or metabolism to hinder nutrient influx and kill bacteria.…”