Drug‐Free Ultrasound‐Responsive Mechanoluminescent Suture Enables On‐Demand Antibacterial Therapy and Enhanced Healing of Infected Wounds

ABSTRACT

Conventional antibacterial sutures commonly rely on antibiotic loading, which may be associated with concerns regarding drug resistance and biocompatibility. To address this challenge, this study developed a drug‐free, ultrasound‐responsive mechanoluminescent suture. By incorporating SrAl₂O₄:Eu^{2 +}, Dy^{3 +} (SAOED) into poly‐ε‐caprolactone (PCL) fibers, PCL/SAOED (PS) sutures were fabricated. Upon ultrasound irradiation, the PS sutures generated reactive oxygen species (ROS) in situ, likely through a mechanoluminescence‐mediated process, resulting in antibacterial activity against Escherichia coli and Staphylococcus aureus without the use of exogenous antimicrobial agents, with PS10 achieving approximately 75% and 79% reduction against the two strains, respectively, while PS20 exceeded 80% in preliminary tests. In vitro experiments indicated that PS sutures exhibited acceptable biocompatibility and measurable ROS‐scavenging capacity. In a rat full‐thickness skin defect model, ultrasound‐activated PS sutures were associated with improved healing outcomes in both infected and non‐infected wounds, with suggestive evidence of antibacterial, anti‐inflammatory, and pro‐angiogenic effects. Overall, this study presents a preliminary strategy that may inform the development of drug‐free, ultrasound‐responsive, on‐demand antibacterial smart sutures, pending further mechanistic and preclinical validation.

Drug‐free, ultrasound‐responsive PCL/SrAl₂O₄:Eu^{2 +}, Dy^{3 +} (PS) sutures generate reactive oxygen species upon ultrasound activation, achieving over 80% antibacterial efficacy against E. coli and S. aureus in preliminary tests without antibiotics. The sutures also show enhanced mechanical strength and are associated with improved infected wound healing, with suggestive antibacterial, anti‐inflammatory, and pro‐angiogenic effects, supporting their further development for surgical site infection management.

1. Introduction

Surgical site infections (SSIs) are among the most common postoperative complications and a leading cause of patient morbidity and mortality, accounting for up to 31% of global healthcare‐associated infections [1]. The burden of SSIs is particularly pronounced in low‐ and middle‐income countries with limited medical resources, where the incidence rate reaches approximately 11.8% [2]. These infections not only pose significant threats to patient health but also impose substantial economic burdens on healthcare systems, as they can prolong hospital stays by an average of 10 days and increase per capita hospitalization costs by over $800 [3].

As critical medical devices for wound closure, suture surfaces are susceptible to bacterial colonization and biofilm formation, which disrupt host immune defenses and trigger persistent inflammation, thereby being recognized as a major risk factor for SSIs [4, 5]. To address this challenge, antibiotic‐loaded sutures (e.g., triclosan‐coated) are widely used clinically. For example, Parikh et al., developed nanofiber sutures by blending poly‐ε‐caprolactone (PCL) with levofloxacin, achieving sustained antibiotic release for 30 days in rat eyes [6]. Similarly, Altun et al., fabricated composite sutures by pressure‐spinning antimicrobial triclosan (Tri) with poly(lactic‐co‐glycolic acid) (PLGA) and polyethylene oxide (PEO), demonstrating antibacterial activity against multiple strains within 24 h [7]. However, such drug‐loaded sutures face significant limitations. (1) an initial burst release followed by poorly controlled drug delivery fails to maintain effective antibacterial concentrations during the critical postoperative period, compromising long‐term efficacy, (2) prolonged bacterial exposure to sublethal antibiotic doses significantly promotes the selection and evolution of drug‐resistant bacteria, (3) exogenous drugs often adversely affect the mechanical properties of sutures [8, 9, 10]. Therefore, there is an urgent clinical need for novel antibacterial sutures that achieve efficient and safe antimicrobial outcomes, reduce infection and resistance risks, and exhibit favorable mechanical properties and tissue healing‐promoting capabilities.

Recently, mechanoluminescent (ML) materials have shown broad potential in biomedical applications. Among these, rare‐earth‐doped strontium aluminate (SrAl₂O₄:Eu^{2 +}, Dy^{3 +}, SAOED), a typical ML material, generates stable visible light under mechanical stimuli such as ultrasound, functioning like a rechargeable optical battery [8, 11]. Leveraging this property, Wang et al., integrated SAOED into commercial denture base resin (DBR) to analyze occlusal forces, while Kim et al., developed self‐healing photodetector (PD) arrays for detecting dental microcracks [12, 13]. Notably, ultrasound‐activated SAOED not only generates reactive oxygen species (ROS) through photosensitization, but also transfers acoustic energy to the surrounding environment, directly exciting oxygen to form ROS such as superoxide anions (•O₂ ⁻), hydroxyl radicals (•OH), and singlet oxygen [14, 15, 16]. Ultrasonic waves induce acoustic cavitation in solutions, causing cavitation bubbles to undergo nucleation, growth, and instantaneous collapse, releasing stored energy as sonoluminescence, heat, and mechanical stress [17, 18]. Pre‐charged ML materials trap carriers in deep/shallow traps within the matrix, and ultrasonic stimulation releases electrons into the conduction band to excite activators, producing persistent fluorescence [17, 19, 20]. The accompanying ROS disrupt bacterial cell membranes, cause DNA damage, and inactivate proteins, effectively killing pathogens like Staphylococcus aureus (S. aureus) without inducing significant resistance [21, 22, 23]. Moreover, SAOED exhibits excellent biocompatibility and low toxicity, making it suitable for in vivo biomedical applications, although its exploration in medical devices remains limited [22, 24].

PCL a biodegradable aliphatic polyester with favorable biocompatibility and low immunogenicity, is widely used in tissue engineering, drug delivery systems, and bio‐sutures [25, 26]. For example, Hosseini et al., incorporated functionalized nanodiamonds and reduced graphene oxide into PCL sutures, enabling temperature sensing between 25°C–40°C for monitoring wound infection and inflammation, such sutures could further reduce bacterial infection risks via antibiotic coatings. Functionally, sutures can also serve as carriers for drugs or growth factors to accelerate wound repair [27]. Hu et al., developed collagen/PCL composite sutures loaded with basic fibroblast growth factor (bFGF), which exhibited favorable mechanical properties, structural stability, and controlled bFGF release in vitro [28]. However, the inherent mechanical weakness of PCL limits its application in load‐bearing sutures [29, 30]. To enhance its performance, studies suggest that incorporating inorganic fillers may promote PCL polymerization and improve rigidity. For instance, Wu et al., synthesized a PCL surface coating that significantly extended suture degradation in vivo while maintaining tensile strength above 20% throughout the experimental period [31]. Notably, Ding et al., reported that SAOED /polymethyl methacrylate (SAOED/PMMA) composites demonstrated superior tensile performance, offering promising prospects for enhancing the mechanical properties of PCL systems by embedding SAOED.

Building on this background, we propose an innovative “drug‐free” antibacterial strategy. By loading SAOED at varying mass ratios (0–20.0 wt.%) onto PCL fibers, we successfully fabricated ultrasound‐responsive PCL/SAOED composite sutures (PS). This design synergistically combines SAOED's ultrasound‐induced ROS antibacterial capacity with PCL's biocompatibility, achieving on‐demand and controllable antibacterial action under ultrasound irradiation. We hypothesize that SAOED incorporation will not only confer this novel functionality but may also synergistically improve the mechanical properties of the PCL matrix. Through systematic characterization of the physicochemical properties, biological functions, and in vivo wound‐healing efficacy of PS sutures, this study aims to provide new insights and experimental foundations for developing next‐generation non‐drug‐dependent smart sutures with active anti‐infection and pro‐healing capabilities.

2. Results and Discussion

2.1. Synthesis and Characterization of SAOED

To obtain SAOED with high crystallinity, the target material was successfully synthesized via a high‐temperature solid‐state reaction under a reducing atmosphere. Previous studies have established that synthesis temperature is critical for crystallinity: significant growth of SrAl₂O₄ and SrAl₁₂O₁₉ microcrystals occurs above 1000°C and 1200°C, respectively, with co‐crystallization of both phases above 1250°C. Consistent with these reports, a sintering temperature of ≥1300°C for 4 h was selected to achieve optimal crystallinity [32]. The crystal structure of the product was initially analyzed using X‐ray diffraction (XRD). As depicted in Figure 1a, all diffraction peaks perfectly matched the standard pattern of monoclinic SrAl₂O₄ (JCPDS No. 34–0379), with no impurity peaks observed. This confirms that the successful doping of Eu^{2 +} and Dy^{3 +} did not alter the host crystal structure of SrAl₂O₄ [33, 34]. Transmission electron microscopy (TEM) images (Figure 1b,c) further reveal its excellent crystallinity, with a measured lattice fringe spacing of 0.405 nm corresponding to the crystallographic plane of monoclinic SrAl₂O₄. The Raman spectrum (Figure 1d) exhibits a characteristic peak at 447.5 cm^{− 1} attributed to the O‐Al‐O bending vibration in [AlO₄]^{5 −} tetrahedra – a distinctive signature of the monoclinic phase. Additionally, a low‐frequency peak near 175 cm^{− 1} correlates with vibrational modes of tetrahedral units, collectively confirming the monoclinic structure of the synthesized product [35, 36, 37].

FIGURE 1.

Microstructural and physicochemical characterization of SAOED Material. (a) XRD pattern of SAOED powder, all diffraction peaks match monoclinic SrAl₂O₄ (JCPDS No. 34–0379), confirming phase purity.(b,c) Low‐ and high‐resolution TEM images, SAOED particle morphology, and lattice fringes (inset) showing a spacing of 0.405 nm. (d) Raman spectrum: characteristic peak at 465 cm^{− 1} assigned to vibrational modes of [AlO₄]^{5 −} tetrahedra in the monoclinic phase. (e) FTIR spectrum: functional group analysis. (f) SEM image. Surface topography and particle distribution. (g–k) EDS elemental mapping. Uniform spatial distribution of Sr, Al, O, Eu, and Dy. (l) XPS survey spectrum. Elemental composition overview. (m–q) High‐resolution XPS spectra, (m) C 1s, (n) Al 2p, (o) O 1s, (p) Sr 3d, (q) Eu 3d (dominant Eu^{2 +} peaks at 1125.2 and 1155.6 eV).

Fourier‐transform infrared spectroscopy (FTIR) was employed to further corroborate the chemical structure (Figure 1e). The broad absorption band between 400–1000 cm^{− 1} corresponds to Al─O bond vibrations, while the peak at 1447 cm^{− 1} originates from residual CO₃ ^{2 −} groups that may have remained from the synthesis process. This indicates the presence of minor impurities from the synthesis but does not affect the overall monoclinic structure of the material [35]. Scanning electron microscopy (SEM) images (Figure 1f) revealed that the SAOED particles comprised irregular microparticles ranging from 4 µm to14 µm in size (Figure S1). The powder surface exhibited numerous pores and cavities attributed to gas escape during combustion. Under high pressure, escaping gas generated pores surrounded by fine particles, with the microstructure displaying characteristic features of the combustion process. The irregular and non‐uniform particle morphology likely resulted from uneven temperature and mass flow distribution within the combustion flame [32]. The measured atomic percentages of Eu^{2 +} and Dy^{3 +} were approximately 1.95% and 0.42%, respectively, with minor deviations attributed to atmospheric oxygen influence during measurement. (Figure S2). This morphology is conducive to the uniform distribution of the within the PCL matrix, ensuring effective mechanoluminescent properties. The elemental mapping (EDS) clearly demonstrated homogeneous distribution of Sr, Al, and O throughout the particles (Figure 1g–k). Additionally, signals from Eu and Dy were detected, directly confirming the successful doping of these rare‐earth elements into the matrix [36, 37].

XPS analysis was performed to determine the valence state of Eu, which governs the luminescent properties of SAOED. The survey spectrum (Figure 1l) confirmed the presence of Sr, Al, O, Eu, and Dy. The high‐resolution Eu 3d spectrum (Figure 1p) exhibited distinct doublet peaks at 1125.85 eV (Eu^{2 +} 3d₅/₂) and 1154.31 eV (Eu^{2 +} 3d₃/₂), unambiguously confirming Eu^{2 +} as the dominant valence state essential for green luminescence [33]. The Sr 3d spectrum displayed two binding energy components corresponding to SrAl₂O₄ (low binding energy) and SrAl₁₂O₁₉ (high binding energy). O 1s spectrum revealed lattice oxygen (O^{2 −}, ∼530.4 eV) and oxygen vacancies (∼532.8 eV) at a ratio of approximately 38.4:61.6, with Dy^{3 +} doping increasing oxygen vacancy concentration. The Dy doping mechanism involves substitution of Sr^{2 +} by Dy^{3 +}, forming defects (Dy_{s r} ^• + V_O ^••) that enhance electron trap density. XPS spectra of other elements (Figure 1m–q) were consistent with their expected valence states [32, 38]. Collectively, these results confirm the successful synthesis of high‐purity, monoclinic‐phase SAOED, providing a robust foundation for its application as a mechanoluminescent unit in sutures.

2.2. Fabrication and Characterization of PS Sutures

To develop functional sutures with enhanced mechanical and bioactive properties, biodegradable PCL was selected as the matrix. A series of PCL and PS were fabricated via wet‐spinning by blending PCL spinning dope with SAOED at varying mass fractions (5–20 wt.%) (Figure 2a). The collected fibers were dried and designated as PCL, PS5, PS10, PS15, and PS20. This scalable process enables potential mass production. Fourier‐transform infrared spectroscopy (FTIR) confirmed the successful integration of SAOED into the PCL matrix. As shown in Figure 2b, compared to the pure PCL spectrum, the PS sutures exhibited multiple characteristic absorption peaks in the fingerprint region (400–1000 cm^{− 1}) attributable to the SrAl₂O₄ lattice. These include the symmetric Sr─O─Al stretching vibration at 846.5 cm^{− 1}, Al─O─Al bridging vibrations at 784.0 and 646.1 cm^{− 1}, as well as [AlO₄]^{5 −} tetrahedral bending vibration at 447.5 cm^{− 1} [39]. These features confirm chemical compositing rather than physical adsorption. Scanning electron microscopy (SEM) revealed morphological differences (Figure 2c). Pure PCL sutures displayed a smooth, dense surface, whereas PS sutures showed uniform roughness due to embedded SAOED particles. Cross‐sectional images confirmed SAOED particles were tightly encapsulated and homogeneously dispersed within the PCL matrix, with no significant agglomeration or detachment [40]. All PS sutures had an average diameter of 350.0 ± 9.1 µm, consistent with clinical No.0 suture specifications. Elemental mapping (EDS) further verified SAOED loading (Figure 2d).

FIGURE 2.

Structural and functional characterization of PS sutures. (a) Schematic of the PS suture fabrication process. (b) FTIR spectra of pristine PCL and PS sutures with varying SAOED incorporation ratios. (c) Surface and cross‑sectional SEM images of PS10, uniform dispersion of SAOED within the PCL matrix. (d) EDS elemental mapping of PS sutures confirming homogeneous SAOED distribution. (e) Tensile strength comparison, PS sutures (different SAOED ratios) vs. commercial silk and Vicryl sutures (size 0). Data are presented as mean ± SD (n = 6 per group). Statistical significance was determined by one‐way ANOVA (F = 135.56, p <0.0001) followed by Dunn–Šídák post hoc test for multiple comparisons. Horizontal lines indicate significant differences, ^**** p <0.0001, ^*** p <0.001, ^** p <0.01, ^* p <0.05. (f) Knot‐breaking force of tested sutures. Data are mean ± SD (n = 6 per group). One‐way ANOVA (F = 183.69, p <0.0001) with Dunn–Šídák post hoc test. (g) Average friction coefficient of suture surfaces. (h) Swelling ratio (%) in PBS after 96 h. Statistical analysis using one‐way ANOVA followed by Dunn–Šídák test showed no significant differences among groups (p >0.05). (i) In vitro degradation rate (%) in PBS over 14 days. One‐way ANOVA with Dunn–Šídák test, p >0.05. (j) Photoluminescence excitation (PLE) and emission (PL) spectra of SAOED powder. (k) Mechanoluminescence excitation spectra of PS sutures under varying ultrasound power densities. (l) Corresponding emission spectra under ultrasound irradiation. (m) Time‐dependent absorbance decay of DPBF at 410 nm, confirming singlet oxygen (¹O₂) generation (n = 3 independent experiments). (n) UV–Vis absorption spectra of DPBF/methanol solution over time.

In summary, morphological and structural analyses confirm the successful fabrication of PS composite sutures with uniform structure and well‐dispersed functional units, establishing a foundation for subsequent functional testing. The integration of SAOED into the PCL matrix not only enhances the mechanical properties but also introduces the potential for ultrasound‐activated antibacterial functionality. Further evaluation of the mechanical properties, biological performance, and in vivo efficacy of these PS sutures will be discussed in the subsequent sections.

2.3. Mechanical Properties and Fundamental Characteristics of PS Sutures

The mechanical performance of sutures is critical for clinical applicability. This study systematically evaluated the mechanical strength, coefficient of friction, degradation, and swelling behavior of PS sutures. Mechanical testing revealed that the incorporation of SAOED significantly enhanced the mechanical properties of PCL sutures. As shown in Figure 2e,f, with the SAOED loading increasing to 10 wt.%, the tensile strength and knot‐breaking force of PS sutures demonstrated an upward trend, exhibiting a 40.51% improvement over pure PCL sutures and surpassing clinically used No.0 Vicryl sutures and silk sutures [41]. This confirms that PS sutures fully meet the strength requirements for clinical applications. The enhancement can be attributed to the homogeneous dispersion of SAOED within the PCL matrix, acting as an effective reinforcing phase. However, when SAOED content exceeded 10 wt.%, particle agglomeration induced internal defects, leading to diminished mechanical properties. An appropriate coefficient of friction is essential for suturing operations [42]. As depicted in Figure 2g, all PS sutures exhibited a coefficient of friction comparable to pure PCL and slightly lower than silk sutures, indicating that SAOED loading did not adversely affect suture passage or tissue drag, thus ensuring favorable surgical handling. Furthermore, degradation and swelling behaviors are pivotal for absorbable materials [43]. Swelling tests (Figure 2h) showed that all sutures absorbed approximately 10% water within 24 h in PBS, demonstrating moderate and consistent swelling beneficial for wound exudate absorption. In vitro degradation experiments (Figure 2i) revealed slow, progressive mass loss (∼7%) after 14 days in PBS, confirming the excellent biodegradability of PS sutures. Collectively, the PS10 group (10 wt.% SAOED) exhibited an optimal balance in mechanical strength, handling, and degradation behavior and was thus selected for all subsequent functional experiments.

2.4. Ultrasound‐Induced Optical Properties of PS Sutures

The core functionality of PS sutures relies on the effective luminescence of SAOED particles under ultrasound stimulation. We first characterized the intrinsic optical properties of SAOED via photoluminescence spectroscopy. As shown in Figure 2j, under 365 nm UV excitation, SAOED emitted a strong broadband peak at 508 nm, characteristic of Eu^{2 +} ions. The luminescence mechanism involves Eu^{2 +} as the activator, where electron transitions from the 4f⁶5d¹ excited state to the 4f⁷ ground state generate visible light emission. Co‐doped Dy^{3 +} ions act as sensitizers, forming energy traps and efficiently transferring absorbed energy to Eu^{2 +}, thereby enhancing emission intensity and duration [44]. Crucially, we confirmed that this luminescence can be effectively triggered by ultrasound. Under ultrasound irradiation (2.0–3.0 W cm^{− 2}), PS sutures generated distinct mechanoluminescent signals (Figure 2k–l), with emission intensity monotonically increasing with ultrasound power [45]. This verifies that SAOED retains its mechanoluminescent properties within PCL fibers and can be remotely activated by external ultrasound. Subsequent studies employed 3.0 W cm^{− 2} ultrasound power to maximize activation. Consistent with previous reports, the mechanoluminescence (ML) intensity of PS sutures exhibited a linear dependence on ultrasound input energy, scaling positively with power density within the tested range (2.0–3.0 W cm^{− 2}). Regarding activation reproducibility, short‐term on/off cycles (15 s on/15 s off) triggered stable and highly repeatable ML responses, confirming the robustness of ultrasound‐triggered luminescence for on‐demand antibacterial applications [46].

2.5. Ultrasound‐Induced Oxidative Properties of PS Sutures

To validate whether ultrasound‐activated PS sutures effectively generate reactive oxygen species (ROS), key to their antibacterial mechanism, we used 1,3‐diphenylisobenzofuran (DPBF) as a selective probe for singlet oxygen (¹O₂) [47]. DPBF irreversibly reacts with ¹O₂ via a Diels‐Alder reaction, forming a colorless product and reducing its characteristic absorbance at 410 nm, the reduction rate correlates with ¹O₂ production.

As shown in Figure 2m, the absorbance of DPBF solution containing PS sutures decreased significantly over ultrasound irradiation (3.0 W cm^{− 2}), while the control group (pure PCL sutures) showed no change. These results suggest that the observed oxidative effect is primarily attributable to ultrasound‐induced ROS generation from SAOED, whereas ultrasound irradiation or PCL alone made only limited contributions under the tested conditions. Nevertheless, the underlying mechanistic interpretation remains preliminary and warrants further investigation.

Moreover, the absorbance decline exhibited a linear relationship with irradiation time (Figure 2n), demonstrating that PS sutures enable sustained and controllable ROS production under ultrasound. In summary, this experiment suggests that PS sutures can generate ROS upon ultrasound activation. However, this observation remains to be validated using quantitative dose–response data.

The successful synthesis of high‐purity, monoclinic‐phase SAOED and their integration into PCL‐based sutures have been demonstrated. The resulting PS sutures exhibit enhanced mechanical properties, favorable handling characteristics, and biodegradable behavior. The ultrasound‐induced luminescent and oxidative properties of PS sutures open new avenues for applications in wound healing and infection prevention, as further explored in the following sections.

2.6. Cytocompatibility and Hemocompatibility of PS Sutures

Biomaterials must undergo thorough biocompatibility evaluation prior to clinical use. We assessed the hemocompatibility of PS sutures through hemolysis testing. Live/dead cell staining provided direct evidence (Figure 3a). After 24 h of culture, cells in both PS sutures and pure PCL sutures groups adhered well and exhibited extended morphology with robust green fluorescence (viable cells), while red fluorescence (dead cells) signals were negligible. This confirms that PS sutures support normal cellular growth and survival.

FIGURE 3.

In vitro biocompatibility and antioxidant properties of PS sutures. (a) Live/dead staining of L929 fibroblasts after 24 h incubation with PS suture extracts, viable cells (green), dead cells (red). Scale bars: 200 µm. Images are representative of three independent experiments. (b) CCK‐8 assay: proliferation vitality of L929 cells cultured with suture extracts for 1, 3, and 5 days. Data are presented as mean ± SD (n = 3 independent experiments, each with 6 technical replicates). Statistical analysis showed no significant differences among groups at any time point (p >0.05). (c) Hemolysis assay: visual results of rabbit RBCs incubated with sutures (positive/negative controls: ±), with quantified hemolysis rate (%). Data are mean ± SD (n = 3). All suture groups exhibited hemolysis rates below 2%, meeting the safety threshold for biomedical materials. (d) Live/dead staining of RAW 264.7 macrophages (24 h extract exposure). Scale bars: 200 µm. Representative images from three independent experiments. (e) CCK‐8 assay: macrophage proliferation under identical conditions. Data are mean ± SD (n = 3 independent experiments, each with 6 technical replicates). No significant differences were observed among groups (p >0.05). (f) DPPH radical scavenging activity: quantitative antioxidant efficiency (%) of suture extracts. Data are mean ± SD (n = 3). PS sutures exhibited significantly higher scavenging activity compared to PCL control (p <0.05). (g) Intracellular ROS clearance, DCFH‐DA fluorescence images of L929 cells under H₂O₂‐induced oxidative stress, demonstrating PS suture‐mediated ROS scavenging. Scale bars for 100 µm. Representative images from three independent experiments.

Furthermore, cytocompatibility was evaluated via in vitro cell culture. Mouse fibroblasts (L929) were co‐cultured with suture extracts for 3 days. CCK‐8 assays (Figure 3b) showed that the absorbance values of all experimental groups increased significantly over time with no statistical difference from the blank control, indicating that PS sutures neither inhibit cell proliferation nor demonstrate cytotoxicity. Quantitative analysis (Figure 3c) revealed hemolysis rates below 2% for PCL and all PS sutures, significantly lower than the 5% safety threshold for biomedical materials [46]. This confirms high blood compatibility. Positive controls appeared bright red due to complete erythrocyte lysis, while negative controls and all suture groups remained transparent. Regarding biocompatibility, Wang et al., incorporated SAOED into commercial dental base resin (DBR, comprising 99% PMMA powder and 1% benzoyl peroxide) and evaluated L929 cell viability/proliferation via MTT assay. Results confirmed that SAOED/DBR composites exhibited no cytotoxicity [12]. Separately, Sepahvandi et al., developed SAOED/CS‐PCL composite scaffolds, finding that scaffolds with 30% SAOED nanophosphors maintained mechanical flexibility and structural integrity while demonstrating excellent cell proliferation capacity and supporting controlled differentiation of retinal neurons (particularly photoreceptors) [48].

In summary, systematic hemocompatibility and cytocompatibility evaluations collectively demonstrate that SAOED incorporation introduces no additional biosafety risks to PCL sutures. PS sutures exhibit favorable biocompatibility, meeting fundamental requirements for implantable medical devices.

2.7. ROS‐Scavenging Capacity and Anti‐Inflammatory Properties of PS Sutures

The microenvironment of chronic non‐healing wounds typically involves excessive reactive oxygen species (ROS) accumulation, which disrupts cellular redox homeostasis, exacerbates inflammation, and impedes tissue repair [49, 50]. Thus, ideal wound dressings or sutures should regulate ROS levels.

The generation and scavenging of ROS form a dynamic equilibrium that is critical for sustaining cellular homeostasis, health, and normal physiological functions. Dysregulation of this balance, either excessive ROS generation or impaired scavenging capacity, can trigger profound pathological cascades, contributing to the onset and progression of various diseases. A comprehensive understanding of the underlying mechanisms governing ROS generation, scavenging, and their intricate crosstalk not only enhances our insights into oxidative stress biology but also offers promising avenues for the development of novel diagnostic tools and targeted therapeutic strategies for oxidative stress‐associated disorders [16, 51]. To validate anti‐inflammatory potential, macrophages (RAW 264.7) co‐cultured with PS sutures extracts maintained high viability (Figure 3d,e), preliminarily indicating favorable cytocompatibility without significant inflammatory response. This anti‐inflammatory property is attributed to the ability of europium‐based nanomaterials to ameliorate wound microenvironments by scavenging excess ROS, thereby promoting angiogenesis [52]. For ROS‐scavenging capacity, DPPH radical scavenging assays were performed. As shown in Figure 3f, PS sutures exhibited potent free radical scavenging efficiency. More critically, at the cellular level, L929 cells stimulated with H₂O₂ (simulating oxidative stress in chronic wounds) showed significantly lower intracellular ROS levels in the PS sutures group compared to controls via DCFH‐DA fluorescence probing (Figure 3g).

PS sutures exhibit distinct dual functions. ROS generation under ultrasound irradiation for antibacterial activity and ROS scavenging under static conditions, which may contribute to anti‐inflammatory effects. While the precise molecular dynamics of this transition remain to be fully elucidated, we propose an energy‐dependent switching mechanism based on our observations. Under static conditions, the rare‐earth dopants in SAOED act as intrinsic antioxidants to scavenge ambient ROS and alleviate oxidative stress, as verified by DPPH assays and intracellular ROS detection (Figure 3f,g), whereas upon ultrasound irradiation, the input mechanical energy drives rapid ROS generation at a rate kinetically exceeding the material's inherent scavenging capacity, shifting the system to a net pro‐oxidant state for effective bacterial elimination; this switchable model is a reasonable hypothesis based on discrete experimental endpoints without real‐time kinetic monitoring of the competition between ROS generation and scavenging, yet the proposed spatiotemporal separation, which restricts antibacterial activity to ultrasound application while maintaining antioxidant protection during healing, offers a plausible account for the coordinated therapeutic efficacy free of functional interference [52].

2.8. Antibacterial Performance of PS Sutures in Vitro

To evaluate the practical antibacterial efficacy of ultrasound‐activated PS sutures, Escherichia coli (E. coli) (Gram‐negative) and S. aureus (Gram‐positive) were selected as model pathogens for quantitative analysis via the colony counting method [3, 53]. The colony‐forming units (CFU) were significantly reduced under ultrasound irradiation, confirming the potent antibacterial activity of PS sutures. This antibacterial performance can be ascribed to the ultrasound‐induced generation of ROS, which effectively disrupts bacterial cell membranes and inhibits bacterial proliferation.

Results demonstrated that ultrasound‐activated PS sutures exhibited potent, dose‐dependent antibacterial effects against both Gram‐negative and Gram‐positive bacteria without requiring exogenous antibiotics. After ultrasound activation 3.0 W cm^{− 2}, 1 MHz, 5 min), significant differences in antibacterial performance were observed across suture groups (Figure 4a,c). Control groups (silk, Vicryl, and pure PCL sutures) showed no notable inhibition of either bacterial strain. In stark contrast, SAOED‐loaded PS sutures displayed exceptional antibacterial efficacy.

FIGURE 4.

Antibacterial performance of PS sutures in vitro. (a, c) Representative agar plate images showing colonies of (a) E. coli and (c) S. aureus after treatment with different sutures under ultrasound activation (3.0 W cm^{− 2}, 1 MHz, 5 min). Images are representative of three independent experiments. (b,d) Quantitative antibacterial efficiency (%) against (b) E. coli and (d) S. aureus based on colony counting. Data are presented as mean ± SD (n = 3 independent experiments). Statistical analysis was performed using one‐way ANOVA followed by Tukey's post hoc test. Statistical significance was defined as ^* p <0.05, ^** p <0.01, ^*** p <0.001; ns, not significant (p >0.05).

Specifically, PS10 achieved antibacterial rates of 75% against E. coli and 79% against S. aureus. Increasing the SAOED loading to 20 wt.% (PS20) further enhanced efficacy, exceeding 80% antibacterial rates for both strains (86.3% for E. coli and 83.0% for S. aureus) (Figure 4b,d). This dose‐dependent effect suggests that antibacterial activity is associated with SAOED content, indirectly indicating a potential relationship between ROS‐generation capacity and bacterial inactivation. Control experiments using ultrasound alone on sutures without SAOED (silk, Vicryl, PCL) showed no bacterial inhibition under identical parameters (3.0 W/cm², 1 MHz, 5 min; Figure 4), confirming that the antibacterial effect is ROS‐mediated rather than thermal. This is consistent with the mild hyperthermia expected from such parameters: 1 MHz ultrasound at 2.4 W/cm² raises muscle temperature by ∼3°C, far below the 60°C–70°C required for effective thermal killing [54]. Mechanistically, the on‐demand ROS generated by PS sutures under ultrasound activation can effectively penetrate biofilms by diffusing through the extracellular polymeric substance (EPS) matrix and oxidatively damaging both bacterial membranes and biofilm scaffolds, consistent with recent reports demonstrating >80% reduction in biofilm biomass via ROS‐mediated strategies [55]. Regarding repeated activation safety, the employed power density (3.0 W/cm²) is three to four orders of magnitude lower than HIFU (1000–20 000 W/cm²) and falls within the established safe window (0.5–3.0 W/cm²) [56, 57]. Multiple excitation cycles using comparable parameters caused no tissue damage and maintained stable luminescence [57]. Moreover, the mechanical index (<1.0) and estimated temperature rise (<2°C) are well below thresholds for cavitation or thermal injury. Collectively, these data support the safety of cumulative ultrasound exposure for activating PS sutures in clinical scenarios.

Critically, this high efficacy was achieved without exogenous antibiotics or antimicrobial agents, a strategy vital for addressing antibiotic resistance while minimizing drug‐related side effects and allergy risks [58]. The on‐demand activation feature is central to intelligent antibacterial sutures, as controllable activation improves drug utilization efficiency, reduces systemic side effects, and delays bacterial resistance development [59]. For instance, conductive sutures with polypyrrole (PPy)/tannic acid (TA) coatings enable electrically controlled drug release to suppress surgical site infections (SSIs) [59]. Similarly, biodegradable elastomers like poly(glycolide‐ε‐caprolactone) (PGCL) allow wireless, heat‐triggered drug release via embedded heating wires and temperature sensors [43]. However, such systems face challenges in complex in vivo environments, electrical stimulation may interfere with neural/muscular functions, and thermal activation risks localized overheating.

Based on the piezoelectric and mechanoluminescent properties of SAOED, we propose two parallel and synergistic pathways for ultrasound‐triggered ROS generation in aqueous environments. The first involves direct sonochemical effects, which are enhanced by SAOED particles acting as cavitation nucleation sites. This intensifies localized extreme conditions, promoting water sonolysis to generate·OH, O₂ ⁻, and ¹O₂. The second pathway is mediated by mechanoluminescence and piezoelectricity: ultrasound‐induced lattice deformation releases trapped charge carriers, leading to Eu^{2 +} excitation and green emission (∼508 nm), which can activate dissolved oxygen to produce ¹O₂. Concurrently, piezoelectric‐induced charge separation generates electron‐hole pairs that drive redox reactions with water and oxygen to generate additional ROS. These synergistic pathways collectively contribute to the observed antibacterial efficacy [17, 60, 61].

The resulting ROS exert dual biological effects: The resulting ROS exert dual biological effects. First, lipid peroxidation attacks polyunsaturated fatty acids in cell membranes, initiating chain reactions that disrupt membrane integrity. Second, direct oxidation of nucleic acid bases and sulfur‐containing amino acids causes DNA breakage and enzyme inactivation. Combined with ultrasound‐induced mechanical membrane disruption, these mechanisms synergistically enhance antibacterial efficacy [21, 22]. This physical strategy effectively circumvents bacterial resistance associated with traditional drug‐release approaches. In summary, antibacterial experiments conclusively demonstrate that PS sutures achieve efficient, broad‐spectrum, and antibiotic‐free “on‐demand” antibacterial action via ultrasound‐triggered ROS mechanisms in vitro.

2.9. In Vivo Wound Healing Performance of PS Sutures

To validate practical efficacy in living organisms, the wound‐healing capacity of PS sutures was evaluated in a rat full‐thickness skin defect model. Macroscopic observation (Figure 5a,b) revealed gradual wound closure in all suture groups within 7 days. However, the PS sutures group (with ultrasound treatment) exhibited superior healing quality, achieving near‐complete wound closure with minimal scarring, significantly outperforming the silk suture control group.

FIGURE 5.

In vivo wound healing performance of PS sutures in a rat full‐thickness skin defect model (standardized 1‐cm‐long incision). (a) Schematic of dorsal wound modeling and suture grouping (Control: Silk; Experimental: US‐activated PS sutures). (b) Macroscopic wound images post‐surgery on Days 1, 3, 5, and 7. Representative images from n = 6 rats per group. (c) H&E‐stained sections (Day 5 & 7; Scale bars: 200 µm): brown arrows: focal necrosis; blue arrows: lymphocyte infiltration; crimson arrows: fibroplasia; cyan arrows: neovascularization; black arrows: necrotic debris. Representative images from three independent tissue sections per sample. (d) Representative CD31 immunohistochemistry (IHC) staining (Scale bars: 100 µm). (e) Quantitative percentage of CD31‐positive area (%). Data are mean ± SD (n ≥ 3 rats per group, with multiple fields quantified per section). ^* p <0.05, ^** p <0.01 vs. control. (f) Microvessel density (MVD) derived from CD31 IHC analysis. Data are mean ± SD (n ≥ 3 rats per group). ^* p < 0.05, ^** p <0.01 vs. control.

To further investigate the underlying mechanisms, histological analysis was performed on tissue samples collected during the healing process. Hematoxylin and eosin (H&E) staining on postoperative day 7 (Figure 5c) revealed significant differences: The silk suture group exhibited uneven epidermal thickness with focal necrosis (brown arrow), disorganized dermal collagen arrangement, and substantial lymphocyte infiltration (blue arrow), indicating persistent inflammation. In contrast, the PS suture group demonstrated well‐organized epidermal architecture, orderly collagen alignment in the dermis, minimal inflammatory cell infiltration, and significant neovascularization (light green arrow) accompanied by connective tissue hyperplasia (dark red arrow), all hallmark features of efficient tissue regeneration. Neovascularization serves as a critical process for delivering oxygen and nutrients essential for tissue repair [62].

CD31 expression, a specific marker for early vascular endothelial cells, was evaluated via immunohistochemistry to determine microvessel density (MVD) at the wound site [62]. Figure 5d,e, and f display immunohistochemical results for CD31 and MVD. At day 7 post‐surgery, the PS sutures group exhibited significantly higher MVD values than the silk suture group, indicating markedly accelerated neovascularization during this interval. Quantitative analysis of MVD via CD31 immunohistochemical staining (Figure 5d–f) demonstrated that the CD31‐positive area in the PS sutures group was 51.5% greater than in the silk suture group at day 5. This evidence directly confirms the potent pro‐angiogenic capacity of PS sutures, providing a crucial material foundation for accelerated wound healing.

The suggested anti‐inflammatory effect of PS sutures, as observed in H&E staining (Figures 5c and 6b), was characterized by reduced lymphocyte infiltration and a more organized collagen architecture compared with the silk control group. These morphological findings may indicate accelerated resolution of inflammation during wound healing. We propose a mechanism based on the intrinsic ROS‑scavenging capacity of PS sutures demonstrated in vitro (Figure 3f,g). Notably, although proteins and inflammatory components in wound exudates may partially absorb or scatter the ∼508 nm mechanoluminescence or act as sacrificial ROS scavengers, the in situ generation of both luminescence and ROS directly at the suture surface, where bacteria preferentially adhere, minimizes these interference effects, as evidenced by stable mechanoluminescence signals in serum‐containing media and the maintenance of >60% antibacterial efficacy even in 10% serum during sonodynamic studies [12].

FIGURE 6.

In vivo therapeutic efficacy of PS sutures in S. aureus‐infected wound model (standardized 1‐cm‐long incision). (a) Macroscopic wound healing progression (Days 0, 3, 5, 7, 10) with silk (control) vs. US‐activated PS sutures. Representative images from n = 6 rats per group. (b) H&E staining (Days 3/7/10; Scale bars: 200 µm): yellow arrows: epidermal defects; crimson arrows: fibroplasia; blue arrows: lymphocyte infiltration; black arrows: necrotic debris. Representative images from three independent tissue sections per sample. (c) Bacterial recovery: S. aureus colonies cultured from wound tissues (Days 1/5/7). (d) CD31 immunohistochemistry (Days 5/10; Scale bars: 100 µm). Representative images. (e) Quantified CD31‐positive area (%). Data are mean ± SD (n ≥ 3 rats per group, with multiple fields quantified per section). ^* p <0.05, ^** p <0.01 vs. control. (f) Microvessel density (MVD) derived from CD31 staining. Data are mean ± SD (n ≥ 3 rats per group). ^* p <0.05, ^** p <0.01 vs. control. (Ultrasound: 3.0 W cm^{− 2}, 1 MHz, 5 min).

In summary, these experiments confirmed in vivo that ultrasound‐activated PS sutures not only effectively promote wound closure but also guide high‐quality, low‐scarring regenerative repair through multiple mechanisms, including improving the inflammatory microenvironment, facilitating orderly collagen remodeling, and significantly accelerating angiogenesis.

2.10. In Vivo Evaluation in S. aureus‐Infected Wound Model

To assess the efficacy of PS sutures in a clinically challenging scenario, a full‐thickness skin defect model infected with S. aureus was established in rats. Macroscopic healing images (Figure 6a) clearly showed delayed healing with evident signs of infection in non‐ultrasound‐treated groups under infectious conditions. In contrast, the ultrasound‐activated PS sutures group demonstrated superior healing outcomes at all time points, with effective infection control. By day 10, dense and uniform epidermal tissue had formed, accompanied by regeneration of more skin appendages (e.g., hair follicles) and minimal scarring.

Histological analysis via H&E staining (Figure 6b) revealed incomplete epidermal structure, moderate epithelial loss (yellow arrow), hyperplastic connective tissue (dark red arrow), and persistent lymphocyte infiltration (blue arrow) in the silk suture control group at day 10, indicating unresolved inflammation. Conversely, the PS sutures treatment group exhibited optimized tissue regeneration, including well‐defined epidermal layers, orderly collagen fiber alignment, and reduced inflammatory cell infiltration, suggesting a potential ability to modulate the inflammatory microenvironment in infected wounds and promote re‐epithelialization and normal tissue remodeling.

The exceptional healing efficacy of PS sutures stems from their ultrasound‐activated antibacterial capacity. As shown in Figure 6c, bacterial cultures from infected wound sites revealed negligible detectable S. aureus survival in the PS sutures group at day 7, with significantly lower bacterial load compared to the silk suture control group. This creates a sterile or low‐bacterial microenvironment conducive to wound healing.

Furthermore, CD31 immunohistochemical staining (Figure 6d–f) indicated that even under infectious conditions, the MVD of the PS group at day 7 was 73.5% higher than that of the silk suture group. This robustly demonstrates that PS sutures not only efficiently eliminate bacteria but also exhibit potent pro‐angiogenic capabilities, supplying ample oxygen and nutrients to damaged tissue to accelerate repair. Collectively, this infected model experiment confirms that ultrasound‐activated PS sutures significantly optimize the healing trajectory of infected wounds through a triple synergistic effect: efficient antibacterial action, inflammation resolution, and angiogenesis promotion, ultimately achieving high‐quality tissue regeneration. It should be noted that the in vivo infection model primarily assessed the clearance of planktonic bacteria. Therefore, the clinical relevance of this approach for biofilm‐associated infections remains to be further investigated.

3. Perspectives

From the perspective of elemental biotoxicity, strontium (Sr) shares metabolic pathways with calcium (Ca), and excessive Sr exposure may disrupt bone metabolism. In SrAl₂O₄, however, Sr exists in a stable oxide form with low solubility and bioavailability [63]. Europium(III) toxicity has been reported to be mainly concentration‐dependent, with limited intracellular uptake, suggesting acceptable local biocompatibility [64]. Nevertheless, systematic investigations of SAOED degradation kinetics, organ accumulation, and long‐term biosafety remain insufficient, particularly with respect to the potential bioaccumulation of rare earth ions such as Eu and Dy. Therefore, long‐term toxicity and cytotoxicity assessments, including apoptosis assays, are warranted, together with evaluations of manufacturing reproducibility and sterilization compatibility across batches. Further studies are also needed to clarify ROS generation mechanisms, antibacterial thresholds, molecular anti‐inflammatory effects, and anti‐biofilm efficacy. Real‐time ROS monitoring, genetically engineered bacterial strains, and systematic optimization of ultrasound parameters should be pursued to improve antibacterial efficiency while ensuring biosafety. Head‐to‐head comparisons with clinically established antimicrobial sutures, such as triclosan‐coated Vicryl Plus, in identical infection models are also needed. Finally, wound‐healing mechanisms should be further quantified and validated in large‐animal models to support future clinical translation (Figure 7).

FIGURE 7.

Schematic overview of ultrasound‐induced PS sutures for on‐demand antibacterial and wound healing therapy: (a) Structural design of PS sutures: Illustration showing the composition and multilayer architecture. (b) Fabrication and application workflow: stepwise schematic of the suture preparation process and its practical deployment for wound closure. (c) Dual‐action mechanism: synergistic antibacterial and anti‐inflammatory effects via ultrasound‐triggered generation of reactive oxygen species (ROS), alongside a conceptual diagram of clinical implementation.

4. Conclusion

This study designed and fabricated a drug‐free, ultrasound‐responsive functional suture, referred to as PS sutures, based on the mechanoluminescent material SAOED. Through a facile co‐spinning process, SAOED particles were uniformly incorporated into PCL fibers, forming structurally dense composite sutures. The incorporation of SAOED served not only as a functional component but also as a reinforcing phase, improving the mechanical properties of the sutures compared with pure PCL, possibly by enhancing interfiber interactions within the composite structure. Preliminary findings suggest that PS sutures can be activated under ultrasound irradiation to generate reactive oxygen species (ROS) in situ, leading to approximately 75% and 79% reduction in bacterial viability against E. coli and S. aureus, respectively, under the tested conditions (with PS20 exceeding 80%), without the use of exogenous antibiotics. This ultrasound‐triggered activation mechanism may help reduce continuous antimicrobial exposure, although direct evidence regarding the prevention of bacterial resistance was not provided in this study. In vitro biological evaluations indicated that PS sutures exhibited acceptable biocompatibility, including low cytotoxicity, favorable hemocompatibility, and measurable ROS‐scavenging capacity, supporting their further evaluation in vivo. In rat full‐thickness skin defect and bacterial infection models, ultrasound‐activated PS sutures were associated with improved wound healing outcomes, with histological findings suggesting reduced bacterial burden, attenuated inflammatory responses, enhanced angiogenesis, and favorable tissue remodeling. It should be noted that the antibacterial assessment primarily involved planktonic bacteria, and the efficacy of PS sutures against mature biofilms remains to be investigated. Overall, these findings suggest that PS sutures represent a promising exploratory strategy for developing drug‐free, ultrasound‐responsive, on‐demand antibacterial surgical sutures. Further studies are needed to clarify the underlying mechanisms, optimize ultrasound activation parameters, evaluate long‐term biosafety, and assess their performance in more clinically relevant infection models before potential clinical translation.

5. Materials and Methods

5.1. Synthesis of SAOED and PS Sutures

5.1.1. Synthesis of SAOED

SAOED were synthesized through a high‐temperature solid‐state reaction. Precursor powders (SrCO₃, Al(NO₃)₃, H₃BO₃, Eu₂O₃, Dy₂O₃, provided by EMPEROR Nanomaterials Co., Ltd., Nanjing, China) were sintered at 1300°C for 4 h under a reducing atmosphere (10% H₂/90% Ar), with H₃BO₃ serving as a flux. The resulting product was subsequently pulverized, sieved, and washed with ethanol to obtain the final SAOED powder.

5.1.2. Synthesis of PS Sutures

Sutures were prepared using wet‐spinning technology. PCL(Mw = 80 000, Sigma–Aldrich) and SAOED at varying mass ratios (0, 5, 10, 15, 20 wt.%) were dissolved in a DMSO/water (4:1, v/v) mixture to form a homogeneous spinning dope (solid content: 0.16 g mL^{− 1}). After degassing, the dope was extruded into a −10°C 75% ethanol coagulation bath via an infusion pump to form nascent fibers. The collected fibers were dried and designated as PCL, PS5, PS10, PS15, and PS20.

5.2. Characterization

The morphology and microstructure of SAOED powder and PS sutures were analyzed using scanning electron microscopy (SEM, Hitachi SU8010) and transmission electron microscopy (TEM, JEOL JEM‐2100F). The crystal structure, chemical functional groups, and elemental composition were characterized by X‐ray diffraction (XRD, Rigaku Homelab), Fourier‐transform infrared spectroscopy (FTIR, Nicolet 6700), and X‐ray photoelectron spectroscopy (XPS, Thermo Scientific). Photoluminescence (PL) and photoluminescence excitation (PLE) spectra of SAOED were recorded using a fluorescence spectrophotometer (Hitachi F4700).

5.3. Suture Performance Testing

5.3.1. Mechanical Properties

Knot‐breaking strength and breaking force of sutures were measured using a universal material testing machine (Labthink i‐Strentek 1510) following ISO 1184–1983. Dynamic friction coefficients were determined with a fiber friction coefficient tester (XCF‐1A).

5.3.2. Swelling and Degradation Behavior

Sutures were immersed in phosphate‐buffered saline (PBS; Solarbio Biotechnology Co., Ltd.) at 37°C [41, 65]. Samples were periodically weighed, and swelling ratio (Equation 1) and in vitro degradation rate (weight loss, Equation 2) were calculated:

$$\mathrm{Swelling}\mathrm{ratio}(\%)=\frac{{\mathrm{m}}_1-{\mathrm{m}}_0}{{\mathrm{m}}_0}\times 100$$ (1)

$$\mathrm{Weight}\mathrm{loss}(\%)=\frac{{\mathrm{m}}_{\mathrm{i}}-{\mathrm{m}}_{\mathrm{r}}}{{\mathrm{m}}_{\mathrm{i}}}\times 100$$ (2)

where m ₀ = initial suture mass, m ₁ = wet mass after immersion, m_i = initial mass, m_r = residual mass post‐immersion.

5.3.3. Ultrasound‐Induced Optical and Oxidative Properties

PS sutures were exposed to ultrasound (2.0–3.0 W cm^{− 2}, 1 MHz), and mechanoluminescent intensity was monitored via fluorescence spectrophotometry. Singlet oxygen (¹O₂) generation efficiency was assessed using the DPBF (1,3‐diphenylisobenzofuran; Solarbio) indicator method, with characteristic DPBF absorbance decay at 410 nm measured by UV–Vis spectrophotometry (Shimadzu UV‐2600).

5.4. Biological Evaluation In Vitro

5.4.1. Cytocompatibility and Anti‐Inflammatory Activity

Mouse fibroblasts (L929) or macrophages (RAW 264.7) were cultured with suture extracts. Cell viability was assessed via CCK‐8 assay. After 24‐h co‐culture, live/dead staining was performed using calcein‐AM (live) and propidium iodide (PI; dead) (Solarbio), followed by fluorescence microscopy (Olympus IX53).

5.4.2. Hemocompatibility

Hemolysis rate was determined by incubating sutures with rabbit red blood cell suspensions and measuring supernatant absorbance at 540 nm.

5.4.3. ROS Scavenging Capacity

Total antioxidant capacity was evaluated via DPPH radical scavenging assay. In an H₂O₂‐induced oxidative stress cell model, intracellular ROS clearance by PS sutures was detected using a DCFH‐DA probe (DPPH and DCFH‐DA from Solarbio).

5.4.4. In Vitro Antibacterial Performance

Antibacterial efficiency against E. coli (ATCC 25922) and S. aureus (ATCC 25923) was evaluated by colony counting method [66, 67]. To rigorously discriminate the contributions of ultrasound alone, SAOED alone, and their combination, multiple control groups were included in the antibacterial assays. Specifically, the following groups were tested under identical conditions: (i) suture‐only groups without ultrasound exposure, including silk, Vicryl Plus, and pristine PCL; (ii) control suture groups with ultrasound treatment, including silk+US, Vicryl Plus+US, and PCL+US; (iii) PS sutures without ultrasound; and (iv) PS sutures with ultrasound activation. All sutures were co‐incubated with bacterial suspensions under the specified conditions (3.0 W cm^{− 2}, 1 MHz, 5 min). After incubation, bacterial suspensions were collected, serially diluted, plated on agar, and incubated overnight at 37°C. Colony‐forming units (CFU) were counted, and antibacterial activity was calculated as:

$$\mathrm{Antibacterial}\mathrm{activity}(\%)=\frac{{\mathrm{N}}_0-{\mathrm{N}}_{\mathrm{x}}}{{\mathrm{N}}_0}\times 100$$ (3)

where N ₀ = colony count from control, N_x = colony count from suture‐treated groups after 24 h.

5.5. In Vivo Animal Experiments

Male Sprague–Dawley rats (n = 18) were randomly assigned to three groups (n = 6 per group) using a random number generator. Randomization was performed by an independent researcher not involved in surgery or outcome assessment, ensuring comparability of baseline characteristics. Rats were housed under standard conditions (22 ± 2°C, 50 ± 5% humidity, 12‑h light/dark cycle) with free access to food and water. All sutures were sterilized by ethylene oxide prior to use. All procedures followed the ARRIVE guidelines and were approved by the Ethics Committee of the School of Stomatology, Lanzhou University (Approval No. LZUKQ‑2025‑088).

A double‑blind design was implemented to minimize observer bias. Sutures (silk vs. PS) were coded by a third party, and the codes were concealed from all personnel involved in surgery, ultrasound treatment, and postoperative evaluations until data analysis was completed. Surgeons and researchers responsible for wound imaging, histological processing, bacterial counting, and immunohistochemical quantification were blinded to group allocation. Group codes were revealed only after all data had been collected and statistically analyzed.

5.5.1. Wound Healing Model

Male SD rats were acclimatized for one month pre‐experiment. Four full‐thickness linear skin incisions (1 cm in length each) were created symmetrically on each rat's dorsum. Control wounds (Groups A/B) were sutured with silk; experimental wounds (Groups C/D) with PS sutures. Experimental wounds received post‐suturing ultrasound (3.0 W cm^{− 2}, 1 MHz, 5 min). Wound healing was monitored at designated time points.

5.5.2. Infected Wound Model

The same animal model was employed. Bilateral incisional skin was tightly sutured intermittently with PS10 sutures and silk sutures, respectively. After suturing was completed, 50 µL of S. aureus solution at a concentration of 1 × 10⁶ mL^{− 1} was implanted into the wound surface. Ultrasound treatment (3.0 W/cm², 1 MHz, 5 min) was applied to the suture sites of wounds in groups B and D, while groups A and C received no ultrasound treatment. Wound healing was monitored at designated time points. After photographing, the surrounding tissues were harvested from the wounds of rats in groups B and D for bacterial content tests, which involved crushing and grinding the tissues, centrifugation, coating plates with 10 µL supernatant, and counting bacteria after overnight culture in an incubator, to evaluate the therapeutic efficacy of PS sutures in infected environments.

5.5.3. Histological Analysis

Wound tissues harvested at specified times were paraffin‐embedded, sectioned, and subjected to hematoxylin‐eosin (H&E) staining and CD31 immunohistochemistry to evaluate tissue regeneration, inflammation, and neovascularization.

5.6. Statistical Analysis

All experiments were independently repeated at least three times, and data are presented as mean ± standard deviation (SD). Prior to statistical analysis, data normality was assessed using the Shapiro–Wilk test, and homogeneity of variances was evaluated using Levene's test. No data transformation or normalization was applied, and no outliers were excluded. For comparisons between two groups, a two‐tailed Student's t‐test was used. For multiple group comparisons, one‐way analysis of variance (ANOVA) was performed when data met the assumptions of normality and homoscedasticity; when ANOVA indicated significant differences (α = 0.05), post hoc pairwise comparisons were conducted using the Dunn–Šídák method to control the family‐wise error rate. In cases where homogeneity of variances was violated, Welch's ANOVA was applied, followed by Games–Howell post hoc test. The sample size (n) for each statistical analysis is explicitly stated in the corresponding figure legend. All statistical analyses were performed using OriginPro 2023 (OriginLab, USA), and a p‐value <0.05 was considered statistically significant. Detailed statistical methods, including test names, post hoc correction methods, and significance levels, are provided in the respective figure legends to ensure transparency and reproducibility.

Funding

This work was financially supported by the National Natural Science Foundation of China (Grant No. 82370926), the School/Hospital of Stomatology, Lanzhou University (NO. 20220850, 071100163, 071100232), Major Project of the Joint Research Fund of Gansu Province (No. 24JRRA941).

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting File: adhm71431‐sup‐0001‐SuppMat.docx.

Data Availability Statement

The data that support the findings of this study are available from the cor‐responding author upon reasonable request.