Ultrasound-mediated piezoelectricity enhancement in bioresorbable polymers

Abstract

Piezoelectric materials can power self-sustained medical devices, but biodegradable systems with high performance remain elusive. We introduce a high-frequency ultrasound treatment strategy that enhances the piezoelectricity of poly-L-lactide (PLLA) via standing-wave-induced crystallization and ferroelectric electret formation. Ultrasound at 1.2 MHz promotes β-form crystal alignment, increasing the piezoelectric coefficient (d₃₃) to 10.8 pC/N, approaching that of non-degradable PVDF. The ultrasound-treated PLLA (US-PLLA) retains full biodegradability and biocompatibility, safely degrading in vivo without organ toxicity. Functionally, US-PLLA enables real-time biosignal monitoring and promotes cardiac recovery after myocardial infarction in rats. This work establishes ultrasound-mediated crystallization as a general route to high-performance biodegradable piezoelectric polymers for transient biomedical systems.

Graphical abstract

Highlights

• •Ultrasound triggers sonocrystallization and ferroelectric electret formation, effectively boosting crystallinity, crystal transition and piezoelectric performance of PLLA.
• •PLLA crystallization under ultrasound relies on solvent-frequency interplay instead of thermal effects to regulate crystal structure evolution.
• •US-PLLA exhibits PVDF-comparable piezoelectricity with full degradability for transient implant medical devices.

1. Introduction

Piezoelectric biomaterials hold promise as the foundation for self-powered, wireless stimulation systems by converting intrinsic biomechanical activities, such as cardiac pulsation, vascular expansion, muscle contraction, and joint motion, into electrical cues [[1], [2], [3], [4]]. In particular, transient implantable piezoelectric materials combining biodegradability, biocompatibility, and mechanical compliance are emerging as attractive platforms for applications ranging from biosensing and tissue engineering to drug delivery, antimicrobial therapy, and tumor ablation [[5], [6], [7], [8]]. However, conventional piezoelectric materials, including inorganic ceramics such as barium titanate (BTO) and lead zirconate titanate (PZT), as well as organic crystals such as poly(vinylidene fluoride) (PVDF), are non-biodegradable, raising concerns of chronic inflammation, infection risk, and the need for secondary removal surgery after their functional lifetime [[9], [10], [11]]. Although pioneering attempts with biodegradable piezoelectric systems, such as glycine-based crystals or poly(L-lactic acid) (PLLA)-derived polymers, have demonstrated proof of concept, their limited piezoelectric output falls short of the demands for effective tissue remodeling [6,12]. These limitations highlight the urgent need for next-generation bioresorbable piezoelectric biomaterials that combine robust electromechanical performance with clinical safety.

The orientation and crystallinity of piezoelectric crystals are highly associated with electromechanical performance. Conventional approaches for improving piezoelectricity, such as electric field poling, mechanical stretching, and interfacial assembly, have been developed to improve the crystalline orientation. Dawnielle Farrar discovered that PBLG can be oriented to obtain an enhanced longitudinal piezoelectric response when subjected to electric field polarization [13]. Mechanical stretching is a powerful technique for modifying the intermolecular forces within polymer crystals, thereby enhancing the piezoelectric properties of nanofibers [4,14,15]. Large-scale interfacial assembly has been employed to synthesize and align the piezoelectric phase of γ-glycine crystals with various polymer substrates, including PVA and PCL [12,[16], [17], [18], [19]]. Therefore, the microscopic orientation of polymer crystals mediated by external fields has been shown to be an effective method for altering the orientation and crystallinity of piezoelectric crystals.

As a type of mechanical wave, sound waves can make objects resonate within an external sound field and have the capacity to drive small particles to spontaneously arrange into regular shapes. As acoustic frequency rises, its corresponding wavelength gradually shortens, allowing it to interact with smaller objects within the sound field. When the frequency reaches ultrasonic levels, sound waves can affect ultrafine objects, such as molecules. In fact, ultrasound fields have been used to promote the crystallization process of compounds, a technique known as sonocrystallization [20]. Thus, ultrasound fields have potential roles in polymer orientation and crystallization.

To date, there have been few studies on using sonocrystallization techniques to regulate the crystallization behavior of piezoelectric polymers, particularly in high-frequency ultrasound. In this work, we aim to establish a High-frequency UltraSound Treatment (HUST) to explore PLLA polymer solution crystallization across a wide frequency range of 5 kHz to 3.6 MHz. PLLA, an FDA-approved medical material, has been extensively used in tissue regeneration due to its excellent biodegradability and biocompatibility [21]. But the piezoelectric response of PLLA is weak when processed through conventional methods such as solvent casting [14], electrospinning [15], and 3D printing [22]. Therefore, we hypothesize that the orientation, crystallinity, and crystal phase of PLLA can be modulated by HUST, and then generate the distinct physicochemical properties, particularly in piezoelectricity.

The piezoelectric activity of PLLA is mainly attributed to its β-form crystals. However, generating the β-form PLLA crystal using conventional pretreatment is challenging. In our previous work, we successfully enhanced the piezoelectricity of PLLA by incorporating another polymer component through a complicated processing [23]. In this study, the pure PLLA membrane solely treated by HUST results in the formation of a unique US-PLLA membrane that naturally develops the β phase. The electromechanical response and piezoelectric coefficient d₃₃ of the US-PLLA membrane are tremendously increased compared to pure PLLA membranes without HUST treatment, approaching the values observed in PVDF, which is currently regarded as the gold standard of non-biodegradable piezoelectric polymer [3,24].

Bioresorbable piezoelectric materials hold significant potential for implantable medical and diagnostic devices [4,5,[14], [15], [16], [17],25]. In this study, we introduce an innovative ultrasound treatment strategy that enhances the piezoelectric performance of US-PLLA by inducing the microscopic orientation of polymer crystals under external fields (Fig. 1). We systematically elucidate how solvent type, ultrasound frequency, and thermal effects modulate orientation crystallinity. The resulting US-PLLA piezoelectric sensor and stimulator demonstrate versatile functionality, enabling pulse and heartbeat monitoring in vitro and facilitating cardiac remodeling after myocardial infarction in vivo, highlighting its promising potential in the field of biomedical engineering.

Fig. 1.

Schematic illustration of an ultrasound treatment strategy that enhances the piezoelectric performance of PLLA by inducing microscopic crystal orientation under an external field. The resulting US-PLLA-based piezoelectric device functions as both a sensor and stimulator, enabling pulse and heartbeat monitoring in vitro and promoting cardiac remodeling after myocardial infarction in vivo.

2. Results and discussion

2.1. HUST method and characterization of US-PLLA

A new homemade HUST processing device was set up by integrating a specific ultrasonic transducer at the bottom of the glass dish. The experimental protocol followed the solvent volatilization casting method. In the absence of ultrasound, the PLLA membrane obtained after solvent volatilization showed a disordered arrangement of molecular chains and remained in an amorphous state. In contrast, the presence of ultrasound promoted the oriented arrangement of PLLA molecules, resulting in enhanced PLLA crystallinity. Importantly, ultrasound-treated PLLA (US-PLLA) revealed the presence of the unique β-form crystal. Moreover, ultrasonic cavitation generates extremely high pressures (∼100 MPa) and electric fields (∼100 kV/m) [26,27], which trigger significant deformation and permanent structural damage to PLLA (cavities in the material). The concomitant electric fields give rise to trapped charges within these defect sites, establishing an electret configuration. Both the β-form crystal and cavities are crucial for its piezoelectric properties (Fig. 2a).

Fig. 2.

HUST method and characterization of US-PLLA. a. The Ultrasound (US) processing device was set up. PLLA with high crystallinity and cavitation was achieved via US-mediated evaporation, while low crystallinity resulted from regular static evaporation. The unique β-form crystal was detected in US-PLLA. b. A clear boundary between US and non-US zones is marked with a yellow line. The US-treated zone presented a rough morphology with cavitation, while the non-US zone exhibited a smooth surface. c-d. SEM observations verified that the ultrasound zone exhibited a rough surface with a spherulitic crystal structure, whereas the non-US zone had a smooth surface. Scale bar: 200 μm. e-f. Polarizing microscope imaging showed the spherulitic crystal structure in US-PLLA. g-h. WAXS indicated a clear diffraction ring in US-PLLA, with the (110/200) crystallographic plane of the α phase nearest to the center, while the diffraction ring in non-US PLLA was blurry, indicating low crystallinity. i. XRD confirmed the presence of the unique β-form crystal in US-PLLA. j. Confocal microscopic images showing cavitation were exhibited in US-PLLA. Scale bar: 100 μm. k-l. The ultrasound frequency obviously affected the crystal structure of PLLA, with the intensity peak being strongest at 1.2 MHz. m. The 2-theta degree around 16.8° slightly increased with higher ultrasound frequencies. n. Piezoelectric coefficient of US-PLLA compared with some classical piezoelectric materials, including collagen [28], Nylon [29], ZnO [30], Rochelle salt [30], and more (further details are provided in Table S1).

The high-frequency ultrasound at 1.2 MHz resulted in a distinct and well-defined boundary on the PLLA membrane between the ultrasound (US) and non-ultrasound (non-US) zones (Fig. 2b), attributed to the focusing effect of ultrasound. SEM observation revealed that the US-treated zone exhibited a rough and cavity-containing morphology, whereas the non-US zone displayed a smooth surface consistent with PLLA (Supplementary Fig. S1), indicating a sharp contrast in crystallinity between the US and non-US zones (Fig. 2c and d).

Polarizing microscope analysis confirmed the formation of polymer spherulites, as the maltase pattern of the US-PLLA sample rotated along with the polarizer, indicating a typical spherulite structure with cavities (Fig. 2e, Supplementary Movie S1). In contrast, no polarized light was transmitted through the non-US PLLA membrane, indicating its low crystallinity (Fig. 2f). WAXS and XRD were employed to distinguish the crystal structures of US-PLLA and non-US PLLA membranes. The diffraction ring of US-PLLA was clear, with the (110/200) crystallographic plane of the α phase nearest to the center. In contrast, the diffraction ring of non-US PLLA was blurry, indicating low crystallinity (Fig. 2g and h). The XRD pattern of US-PLLA confirmed the presence of typical crystallographic planes (110/200) and (203) of the α phase, as well as planes (002) and (023) of the β phase (Fig. 2i). The appearance of the β crystallographic plane indicated that the US-PLLA membrane possessed piezoelectric potential. FTIR quantitative analysis was performed to evaluate the ratio of β crystals. The ratio of β crystals to the sum of α and β crystals was 57.69% for US-PLLA. In contrast, pristine PLLA contains almost no β-phase crystals (Supplementary Fig. S2). The crystallinity (Xc) of the samples was evaluated using DSC. The Xc of US-PLLA was 31.73%, and the Xc of PLLA was 25.14% (Supplementary Fig. S3). The β-crystal content can be calculated via the product of total crystallinity and β-phase fraction. The β-crystal content of US-PLLA at 1.2 MHz was 18.31% (Supplementary Fig. S4). Confocal microscopic images further confirmed cavitations were exhibited in US-PLLA (Fig. 2j). The US-PLLA membrane exhibited good flexibility and was able to be bent by hand (Supplementary Movie S2). Analysis of the tensile stress-strain curve revealed that US-PLLA possesses a higher elastic modulus and tensile strength. The elongation at break for the US-PLLA and PLLA showed no significant difference (Supplementary Fig. S5). The crystallinity degree of US-PLLA caused PLLA molecules to be more closely packed, although the spherulites introduced roughness and flaws. The counterbalancing positive and negative structural effects endow US-PLLA with enhanced mechanical strength while maintaining comparable flexibility to untreated PLLA.

Supplementary data related to this article can be found online at https://doi.org/10.1016/j.bioactmat.2026.06.039

The following are the Supplementary data related to this article:

To determine the optimal frequency of PLLA acoustic crystallization, an adjustable frequency range from 5 kHz to 3.6 MHz was applied in our processing system, covering a total of 24 frequencies (Supplementary Fig. S6). A small stationary wave was generated on the PLLA solution surface and remained stable after the ultrasound was activated (Supplementary Fig. S7, Movie S3). XRD analysis of 24 different US-PLLA membranes confirmed that the characteristic peak at 16.8° was strongest at a drive frequency of 1.2 MHz, indicating the highest degree of crystallinity among all 24 frequencies (Fig. 2k and l, Supplementary Fig. S8). Additionally, the 2-theta degree around 16.8° is slightly elevated with higher ultrasound frequencies, suggesting minor variations in US-PLLA crystallization at different frequencies (Fig. 2m).

Supplementary data related to this article can be found online at https://doi.org/10.1016/j.bioactmat.2026.06.039

The following are the Supplementary data related to this article:

In general, ultrasonic irradiation of PLLA solution imposes alternating compressive and tensile acoustic pressures, which drive two core mechanisms: ultrasonic cavitation and acoustic streaming [31,32]. During the tensile phase of the acoustic cycle, polymer chains are pulled apart. When the ultrasonic intensity exceeds a critical threshold, this tension exceeds the solvent's local strength, initiating cavitation bubble formation. These bubbles expand and merge under negative pressure cycles, then collapse violently during positive compression phases, generating extremely high pressures (∼100 MPa) and electric fields (∼100 kV/m) [26,27]. Ultrasonic cavitation generates short-lived yet extremely high-pressure waves, which trigger significant deformation and permanent structural damage to PLLA. The concomitant electric fields give rise to trapped charges within these defect sites, establishing an electret configuration. Furthermore, despite the bulk centrosymmetric nature of PLLA, local regions adjacent to chemical and physical defects may adopt non-centrosymmetric crystalline phases. Simultaneously, acoustic streaming induces bulk flow and shear within the solution, promoting chain alignment and mixing. Importantly, acoustic energy attenuates with propagation distance due to absorption and scattering by the molten medium, creating a spatial pressure gradient that modulates the intensity of cavitation and streaming along the propagation path.

Against this physical background, the optimal performance of 1.2 MHz can be mechanistically understood as a favorable balance between cavitation activity, shear generation, and chain relaxation dynamics. At 1.2 MHz, the acoustic period matches the characteristic relaxation time of PLLA chains in the melt, enabling efficient conversion of acoustic energy into oriented chain motion without excessive disordering caused by intense cavitation. Higher frequencies produce overly frequent and energetic bubble collapse events, which disrupt ordered assembly and induce excessive chain scission. In contrast, lower frequencies generate relatively weak shear and insufficient spatial modulation to drive consistent chain alignment. Consequently, 1.2 MHz represents a frequency window where cavitation remains moderate (avoiding destructive turbulence), acoustic streaming provides effective shear for orientation, and the spatial pressure gradient ensures homogeneous structural development—ultimately promoting the formation of oriented β-crystals and improving overall sample anisotropy.

We measured the piezoelectric coefficient d₃₃ of US-PLLA to be ∼10.8 pC/N using a quasi-static d₃₃ testing instrument. The d₃₃ value of US-PLLA is competitive with that of PVDF, indicating that US-PLLA possesses good piezoelectric conversion potential (Fig. 2n).

Ultrasound can enhance the crystallization of compounds, and this principle has been extensively applied in the chemical and food industries [33]. In this work, we applied the HUST method to improve the crystallinity of PLLA and simultaneously vary its physicochemical properties. The US-PLLA membrane obtained via solvent evaporation under the HUST method possesses higher crystallinity and a cavity-containing structure. The crystallinity of PLLA is significantly lower when ultrasound is removed, while other conditions remain unchanged. This suggests that the increase in PLLA crystallinity is caused by ultrasound through the sonocrystallization effect. In addition, a PLLA-based ferroelectret was created by creating cavitation through ultrasound treatment. The ultrasound frequency notably affects the crystallinity of US-PLLA, and we finally identified the optimal frequency for PLLA as 1.2 MHz. More importantly, the specific β-form of PLLA crystallization is generated at 1.2 MHz, implying the potential piezoelectricity of US-PLLA, as the β form is primarily responsible for the piezoelectric properties of PLLA.

2.2. Interaction mechanism for enhanced crystallization via HUST

The solvation effect, generated by the interaction between solute and solvent, plays a central role in the crystallization behavior of the solute. A stronger solvation effect makes it more difficult for the solute to form nuclei in a saturated solution. PLLA, as a polar polymer, has its crystallization behavior tremendously influenced by the type of solvent used. In this study, we selected two PLLA solvents, DCM and HFIP, to explore their solvation effects and investigated the crystallization behavior of PLLA in these different solvents via molecular dynamics simulation. Our findings showed that the DCM solution was able to enhance PLLA crystallinity under the HUST method, whereas the HFIP solution did not promote PLLA crystallinity under the same conditions (Fig. 3a and b). XRD analysis further confirmed this phenomenon in two different solvents of DCM and HFIP (Fig. 3c).

Fig. 3.

Molecular mechanism of PLLA crystallinity enhancement and PLLA-based ferroelectret formation mediated by HUST. a-b. Two US-PLLA membranes were fabricated using DCM and HFIP solvents, respectively. The typical crystal area did not form in the center of the HFIP solvent. c. XRD analysis confirmed that PLLA membranes had higher crystallinity in DCM than in HFIP. d. Molecular structures of (d1) PLLA, (d2) HFIP, and (d3) DCM were shown, with C atoms in deep green, H in white, O in red, F in cyan, and Cl in pale green. e. Solvent-solute interaction energies for DCM and HFIP were calculated using molecular dynamics simulation. f-g. Representative snapshots of solute-solvent equilibrium systems for DCM and HFIP were presented. h. Finite element analysis of ultrasound diffraction patterns showed that the pattern became more condensed as the ultrasound frequency increased from 2.4 kHz to 1.2 MHz. i. An energy diagram schematic indicated that ultrasound breaks through the energy barrier for polymers in a fully dissolved state, allowing crystalline structures to form using the thermodynamic process. j. Experimental thermal imagery equipment was set up. k. Thermal images of PLLA solution in a glass dish over time confirmed an optimal solvent evaporation of 70 min at around room temperature. l. The small temperature change in the evaporation system indicates that the enhancement of PLLA crystallinity is not due to the thermal effect of ultrasound.

We continued to investigate the interaction energy of PLLA with DCM and HFIP using molecular dynamics simulation (Fig. 3d–g). The interaction energy between PLLA and HFIP was as high as 1332.88 kcal/mol, whereas the interaction energy between PLLA and DCM was only 240.37 kcal/mol (Fig. 3e). We also found that hydrogen bonds were formed between PLLA polymer chains and HFIP solvent molecules (Fig. 3g), leading to high interaction energy in the HFIP system. On the contrary, no hydrogen bonds were generated between PLLA and DCM (Fig. 3f). Hence, the diffusion ability of the PLLA polymer chain in DCM was strong, facilitating the formation of crystal nuclei. The radial distribution function indicated that local coordination interaction existed between the O1 and O2 atoms of PLLA and the oxygen atoms of HFIP, with the interaction between O2 of PLLA and the oxygen of HFIP being more significant. However, there was no significant interaction between the O1 and O2 atoms of PLLA and the chlorine atoms of DCM (Supplementary Fig. S9). We also prepared specimens using chloroform with slightly higher polarity. The results reveal that solvents of moderately elevated polarity degrade the piezoelectric performance of samples. The result demonstrated that solvents with weaker polarity are more conducive to the piezoelectric performance of US-PLLA via a HUST method (Supplementary Fig. S10).

Finite element analysis was used to investigate the ultrasound diffraction pattern across a frequency range from 2.4 kHz to 1.2 MHz (Fig. 3h). As the ultrasound frequency increased, the pattern became denser and tinier, indicating that high-frequency ultrasound affects microscale materials. This acoustic diffraction pattern resembles Chladni figures formed under audible sound waves; here, analogous microscale patterns emerge under high-frequency ultrasound, explaining how ultrasonic fields rearrange PLLA molecular chains. This study extends cymatics research into the high-frequency ultrasonic regime. We hypothesize that ultrasound induces the sonocrystallization of PLLA from a thermodynamics perspective, as depicted in the energy diagram in Fig. 3i. During the process of sonocrystallization, ultrasound provides sufficient energy for polymer molecules to overcome the stabilizing barrier, leading to the formation of crystalline nuclei and facilitating further crystallization. Moreover, Finite element analysis revealed how cavitation formed in the US-PLLA matrix. The PLLA crystals were grown following the ultrasound diffraction pattern; the pattern guiding and the ultrasound cavitation effect facilitated the cavitation formation in the US-PLLA matrix.

Monitoring the temperature change during solvent evaporation is essential during ultrasound treatment. The optimal ultrasound treatment time can also be determined using thermal imagery. Subtle temperature differences were recorded in the central regions of the ultrasound-treated area during the evaporation of PLLA solution in a glass dish (Fig. 3j). Solvent evaporation typically leads to a decrease in temperature. When the PLLA solution was added to the glass dish, the temperature in the dish dropped immediately due to the evaporation of DCM (Fig. 3k). Temperature fluctuations resulted in alternating light and dark patterns on the surface of the PLLA solution, as observed in the thermal imagery. After 10 min of ultrasound treatment, the temperature of the PLLA solution was significantly lower than the ambient temperature due to continuous DCM volatilization (Fig. 3k, Supplementary Fig. S11). After 70 min of ultrasound treatment, the low-temperature area in the glass dish gradually disappeared and approached the ambient temperature, as DCM had almost completely volatilized. Therefore, the ultrasound treatment time in this work was set to 70 min. Additionally, the ultrasound treatment elevated the solution temperature while DCM evaporation caused a decrease in temperature, suggesting a balance between DCM evaporation and ultrasound heating. Hence, the temperature in the ultrasound treatment area did not exceed 30 °C throughout the treatment process (Fig. 3l), which is lower than the boiling point of DCM and significantly below the glass transition temperature of PLLA. Therefore, the thermal effect of ultrasound is insufficient to affect PLLA crystallinity.

2.3. Piezoelectric properties of US-PLLA

The piezoelectric property of PLLA primarily arises from its β-form crystal structure. However, obtaining β-form PLLA through conventional processing methods such as solvent casting [14], electrospinning [15], and 3D printing is challenging [22]. In this study, we found that the US-PLLA membrane derived from HUST possessed the β-form crystal, which exhibited a higher degree of oriented crystallinity in comparison with the traditional α-form crystal (Fig. 4a). When subjected to the same force, the β-form crystal of PLLA generated more electricity due to its polarity deformation (Fig. 4b). Consequently, we proceeded to evaluate the piezoelectric response of the US-PLLA membrane.

Fig. 4.

Direct and inverse piezoelectric properties of US-PLLA. a. The β-form crystal of US-PLLA was formed via HUST. b. The β-form crystal of PLLA generates more electricity with the same force. c. The configuration of the dual-mode piezoelectric response evaluation system. d. The piezoelectric sensor of US-PLLA was packaged with a multi-layer structure. e. The drive voltage curve was designed for both direct and inverse piezoelectric evaluation. f-h. The direct piezoelectric response of non-US PLLA (f), US-PLLA (g), and PVDF (h) was approximately 0.5 V, 2.2 V, and 2.8 V, respectively. i, j. When a finger pressed on the US-PLLA piezoelectric sensor, the output voltage was 0.013 V, dropping to 0 after the finger was lifted. k. The background noise of the piezoelectric sensor without drive voltage. l-n. The inverse piezoelectric response of non-US PLLA (l), US-PLLA (m), and PVDF (n) was 0.2 V, 1 V, and 1.1 V, respectively. o. The loudspeaker application of the US-PLLA piezoelectric sensor exhibited inverse piezoelectric properties.

An electromechanical evaluation system was set up (Fig. 4c), and the packaged structure of the piezoelectric sensor is shown in Fig. 4d. Briefly, an ultrasonic transducer was used as a resonator, maintaining constant contact with the piezoelectric sensors to eliminate contact electrification. The longitudinal pressure was applied to the piezoelectric sensors through the vibration of the piezoelectric ceramic plate. Additionally, the ultrasonic transducer could function as a vibration sensor. Therefore, within the same test system, we applied a driving voltage to the US-PLLA piezoelectric sensors to generate vibration and used an ultrasonic transducer to detect the vibration produced by the US-PLLA piezoelectric sensors. So, the inverse piezoelectric response was evaluated [34].

For direct piezoelectric testing from force to electricity, the output signal from the functional generator remained consistent (Fig. 4e). Piezoelectric sensors made from US-PLLA, non-US PLLA, and PVDF were prepared and tested, respectively. The output voltage amplitude of non-US PLLA was the lowest at 0.5 V, while US-PLLA showed approximately 2.2 V, comparable to the 2.8 V observed with PVDF used as a positive control (Fig. 4f–h). Subsequently, the US-PLLA piezoelectric sensor was utilized as a pressure detector to measure finger press (Fig. 4i and j). When the finger pressed on the US-PLLA piezoelectric sensor, the output voltage measured 0.013 V. Upon removing the finger, the voltage dropped to 0 V (Supplementary Movie S4).

Supplementary data related to this article can be found online at https://doi.org/10.1016/j.bioactmat.2026.06.039

The following are the Supplementary data related to this article:

For inverse piezoelectric testing from electricity to force, we adopted ultrasonic transducers to measure the pressure induced by the deformation of samples under electric field excitation. Samples with superior piezoelectric performance can generate greater pressure under electric field excitation, which in turn produces a larger voltage signal from the ultrasonic transducer. No signaling waveform was displayed on the oscilloscope when the functional generator was turned off, indicating the background noise within the system (Fig. 4k). The signal output of non-US PLLA was close to this background noise, suggesting that non-US PLLA exhibited no inverse piezoelectric response (Fig. 4l). In contrast, the signal amplitude of the US-PLLA output was 1.0 V, which closely matched the 1.2 V observed with PVDF (Fig. 4m and n). These findings confirmed that US-PLLA exhibited a similar inverse piezoelectric response to PVDF. More importantly, the US-PLLA piezoelectric sensor demonstrated the capability to function as a loudspeaker for playing music, producing sound frequencies ranging from 6 to 11 kHz. When a signal was input to the US-PLLA piezoelectric sensor, the music played clearly with a predominant frequency (Fig. 4o and Supplementary Audio S1). The signal amplitude was maintained at 50 V, with music becoming louder as the frequency increased and weaker as it decreased. Finally, the piezoelectric coefficients d₃₃ for non-US PLLA, US-PLLA, and PVDF were approximately 0.9, 10.8, and 13.8 pC/N, respectively, consistent with the results from direct and inverse piezoelectric evaluations (Supplementary Fig. S12, Supplementary Movie S5). The ultrasound-treated regions exhibit stable piezoelectric coefficients d₃₃. The untreated area shows nearly no piezoelectric response, and slightly higher values appear in the transition zone (Supplementary Fig. S13, Supplementary Movie S6), further validating the effect of ultrasound treatment.

Supplementary data related to this article can be found online at https://doi.org/10.1016/j.bioactmat.2026.06.039

The following are the Supplementary data related to this article:

Several vital factors influence the piezoelectric coefficient of materials, involving dipole moment, crystallinity, and orientation [25,35,36]. In the case of piezoelectric polymer materials, enhancing crystallinity corresponds to improving micro-scale orientation, thereby potentially increasing the macro-scale piezoelectric response. Specifically, the β-form crystal of PLLA is induced through HUST treatment, representing the piezoelectrically active phase due to its highly ordered dipole arrangement compared to the α-form crystal. Moreover, ultrasonic cavitation generates short-lived yet extremely high-pressure waves, which trigger significant deformation and permanent structural damage to PLLA. The ultrasonic cavitation electric fields give rise to trapped charges within these defect sites, establishing an electret configuration. Taken together, HUST treatment introduced the β-form crystal and the electret state to the PLLA matrix, enhancing the piezoelectric coefficient of the PLLA material. The HUST method achieves competitive piezoelectric performance with simpler operation, lower cost, and better scalability than conventional PLLA modification techniques. Traditional strategies, including electrospinning, hot pressing, and high-voltage poling, rely on harsh processing conditions. Electrospinning requires 10–20 kV high voltage and strict environmental control, producing PLLA with d₃₃ of 2.4 pC/N but poor uniformity and low scalability [17]. As confirmed in previous literature [37], dense hot-pressed PLLA without mechanical stretching shows nearly no longitudinal piezoelectric coefficient d₃₃. Furthermore, high-voltage poling alone fails to activate the piezoelectric performance of PLLA. In contrast, HUST realizes efficient PLLA dipole alignment and crystallization under mild ambient conditions. The optimized HUST-PLLA exhibits a stable d₃₃ of 10.8 pC/N. HUST avoids the limitations of harsh multi-step processing and enables scalable fabrication of uniform piezoelectric PLLA films. Collectively, HUST is a facile, cost-effective, and scalable alternative to traditional piezoelectric processing technologies.

2.4. In vivo monitoring application of US-PLLA

In vivo application of piezoelectric materials remains challenging primarily because of their limited biocompatibility and non-biodegradability [4,38,39]. However, the recent development of US-PLLA with enhanced piezoelectric properties has shown promising advancements. This material demonstrates superior biocompatibility, effectively supporting the adhesion and growth of electrically sensitive cardiomyocytes (Fig. 5a and b). Furthermore, it successfully maintains cardiomyocyte activity and promotes consistent beating (Fig. 5c and d). The US-PLLA disc was immersed in a proteinase K solution (an environment that accelerates degradation) to demonstrate obvious degradation over time (Fig. 5e and f). The subcutaneous implantation of US-PLLA for 1 month demonstrated no significant inflammation and toxicity in vital organs such as the heart, liver, spleen, lung, kidney, and skin (Fig. 5g and h). To further evaluate biocompatibility, we performed comprehensive serum biochemical tests for alanine aminotransferase (ALT), uric acid (UA), and total cholesterol (CHO) (Supplementary Fig. S14). No obvious abnormalities were found in the PLLA and US-PLLA implantation group and the Sham operation group. Immunostaining for an inflammatory marker (iNOS) was performed to further evaluate the inflammatory response of PLLA and US-PLLA (Supplementary Fig. S15). The results revealed that PLLA and US-PLLA induced no significant inflammatory reactions relative to the Sham group. All these results demonstrated that US-PLLA possesses good biocompatibility. Piezoelectric stability of biodegradable piezoelectric materials is critical when exposed to body fluids. US-PLLA samples were incubated in simulated body fluid (SBF, pH 7.4, 37 °C) for up to 4 weeks, with weekly measurements of d₃₃ values. The results demonstrate that the piezoelectric coefficient remains above 55% of the initial value within the 4-week treatment window, indicating US-PLLA exhibits good piezoelectric stability (Supplementary Fig. S16).

Fig. 5.

Biocompatible and biodegradable evaluations of US-PLLA and its potential application. a-b. The US-PLLA substrate enabled the support of the adhesion and growth of electrically sensitive cardiomyocytes. Data are presented as mean ± SD (n = 3). ∗p < 0.05 and ∗∗∗p < 0.001. c-d. Calcium transient staining indicated that the US-PLLA substrate was able to maintain cardiomyocyte activity and consistent beating. e-f. Degradation studies of US-PLLA discs in a proteinase K solution demonstrated significant degradation over time. Data are presented as mean ± SD (n = 3). g-h. Subcutaneous implantation of US-PLLA showed no significant inflammation and toxicity in vital organs, including the heart, liver, spleen, lung, kidney, and skin. i. A piezoelectric sensor made from US-PLLA effectively monitored real-time human surface pulses. j. The biocompatible sensor was successfully implanted to monitor the rat's heartbeat in situ. Some components in this figure, such as photos of rats and organs, were created in BioRender. K, K. (2026) https://BioRender.com/f0ptimp

The specific piezoelectric sensor was constructed using US-PLLA as a core component. The piezoelectric responses of US-PLLA were recorded using a Tonghui 2690 electrometer and a Keithley DMM6500 multimeter. The output voltages generated from US-PLLA under different forces from 2.5-15 N were recorded (Supplementary Fig. S17a). The output voltages gradually increased with the rise of the force, demonstrating favorable force sensitivity as well as stable and reversible electrical signals. Sensor sensitivity of the US-PLLA was calculated from the voltage-pressure curve, defined as the slope of the fitting plot (Supplementary Fig. S17b). The US-PLLA achieved a high sensitivity of 0.182 V/N and exhibited excellent linearity. Since reproducibility and reliability are essential for the long-term service of the US-PLLA, we conducted a 3000-cycle compression test on the US-PLLA sensor (Supplementary Fig. S17c). Benefiting from the outstanding piezoelectric stability of the material, the output voltage waveform remained stable without any signal attenuation during the entire test, verifying its superior sensing stability. This sensor effectively monitors real-time human surface pulses (Fig. 5i, Supplementary Movie S7). It can also be implanted to monitor a rat's heartbeat in situ (Fig. 5j, Supplementary Movie S8-9), indicating the US-PLLA could convert the in situ heartbeat into electrical stimulation, highlighting the application potential of US-PLLA in cardiac tissue engineering.

Supplementary data related to this article can be found online at https://doi.org/10.1016/j.bioactmat.2026.06.039

The following are the Supplementary data related to this article:

Biodegradable piezoelectric materials are increasingly garnering attention for their immense potential in implantable medical and diagnostic devices [25,38]. Unlike traditional piezoelectric polymers or ceramics, which are typically bioinert and non-biodegradable and may require a second surgery for removal due to risks such as inflammation and potential long-term complications. The developed US-PLLA can not only function as a self-powered device in vivo but also can gradually degrade and eventually be absorbed by metabolism after completing its service period. Therefore, US-PLLA with enhanced piezoelectricity and biodegradability holds great promise in the field of biomedical engineering. Recent high-performance biodegradable amino acid molecular crystals deliver high piezoelectric coefficients but dissolve and lose piezoelectric functionality immediately upon contact with aqueous or bodily fluid environments, along with intrinsic brittleness and poor mechanical stability [12]. Peptide-based piezo-materials exhibit good flexibility yet are limited by insufficient structural stiffness, complex fabrication procedures, and unstable piezoelectric output under wet conditions [40]. US-PLLA achieves favorable piezoelectric and mechanical properties while possessing unique tunable long-term degradability and superior biosafety, overcoming the common drawbacks of rapid performance decay and structural failure in existing biodegradable piezo-materials. Furthermore, the facile and scalable ultrasonic fabrication strategy provides US-PLLA with distinct advantages for practical clinical translation.

2.5. In vivo therapeutic application of US-PLLA

To evaluate the therapeutic potential of US-PLLA in vivo, we applied the US-PLLA to the infarcted myocardium of rats. The piezoelectric microenvironment generated by US-PLLA, which converts the mechanical force of cardiac contraction into local electrical signals, was expected to modulate post-infarction remodeling. Echocardiographic analysis revealed that US-PLLA significantly improved left ventricular function, as indicated by enhanced ejection fraction (EF) and fractional shortening (FS), while preserving LVIDs and LVIDd, thereby preventing post-infarct ventricular dilation (Fig. 6a–f).

Fig. 6.

Biocompatible and biodegradable evaluations of US-PLLA and its application in treating myocardial infarction. a. Schematic illustration of US-PLLA treating myocardial infarction. b. Left ventricular echocardiography after different treatments for 4 weeks. c-f. Different typical left ventricular echocardiographic parameters of different treatment groups. Data are presented as mean ± SD (n = 3). ∗p < 0.05 and ∗∗∗p < 0.001. g. Masson trichrome staining showed the myocardium (red) and fibrous tissue (blue) of sections of hearts in different treatment groups. h. The expression of CX43 was significantly upregulated in the US-PLLA group, indicating enhanced myocardial integration and electrical connectivity. Scale bar: 100 μm. i. WGA staining showed smaller cardiomyocyte cross-sectional areas in the US-PLLA group compared with the PLLA and MI groups. Scale bar: 50 μm. j. Immunostaining with anti-CD31 and anti-αSMA antibodies was performed, which highlighted a pronounced enhancement of microvessel density in the US-PLLA group compared with the MI and PLLA groups. Scale bar: 100 μm.

Masson's trichrome staining demonstrated that US-PLLA markedly reduced fibrotic area and mitigated ventricular wall thinning compared with both untreated MI and PLLA controls (Fig. 6g). Mechanistically, US-PLLA enhanced expression of connexin-43 (CX43), suggesting improved electrical coupling between cardiomyocytes (Fig. 6h, Supplementary Fig. S18a). Wheat germ agglutinin (WGA) staining further revealed reduced cardiomyocyte hypertrophy, indicating attenuation of maladaptive remodeling (Fig. 6i, Supplementary Fig. S18b). Importantly, immunostaining for CD31 and α-SMA showed robust neovascularization in the US-PLLA group, highlighting its ability to promote vascular regeneration within the infarct zone (Fig. 6j, Supplementary Fig. S18c). We hypothesize that the improved cardiac function is driven by physiologically relevant piezoelectric electrical signals generated by the US-PLLA scaffold in response to native cardiac mechanical motion. The scaffold generates local alternating electric potentials that closely match the amplitude and frequency of endogenous myocardial bioelectric fields and mechanoelectrical feedback rhythms. These low-intensity physiological signals regulate the functions of cardiomyocytes and endothelial cells through voltage-gated ion channels and calcium-dependent signaling cascades. Specifically, such electrical stimulation upregulates CX43 expression to restore intercellular electrical coupling, activates pro-angiogenic pathways to facilitate neovascularization, and re-establishes intracellular calcium homeostasis to inhibit pathological cardiomyocyte hypertrophy. We hypothesize that the piezoelectric signals generated by US-PLLA activate the Ca²⁺ influx pathway (via voltage-gated Ca²⁺ channels), which in turn regulates downstream signaling pathways (PI3K/Akt, NF-κB, MAPK/ERK) to promote cardiomyocyte survival, angiogenesis, and electrical coupling. Overall, the piezoelectric effect compensates for impaired endogenous bioelectric cues after myocardial injury, thereby promoting electrical synchronization, angiogenesis, and the alleviation of adverse cardiac remodeling.

It is well documented that the acidic microenvironment resulting from PLLA degradation, especially in the already inflammatory and hypoxic post-MI milieu, may theoretically aggravate local acidosis and amplify inflammatory cell infiltration [41]. We implanted US-PLLA onto the surface of healthy hearts to investigate the inflammatory response induced by its degradation products, in the present 4-week study, no obvious excessive inflammatory response or severe tissue damage was observed (Supplementary Fig. S19), which may be attributed to the relatively slow degradation rate of PLLA in the early stage, during which only a small amount of lactic acid is released under the environment of body fluids (Supplementary Fig. S20) and can be gradually metabolized through the tricarboxylic acid cycle without significant local accumulation [42].

Electrical stimulation has long been recognized as a powerful modulator of cardiac repair [43], yet existing piezoelectric polymers such as PVDF and PVDF-TrFE remain clinically impractical due to their permanent, non-degradable nature [44]. Here, we introduce an ultrasound-engineered PLLA with markedly enhanced piezoelectricity, achieved through the generation of β-crystals and void-based dipoles. This strategy elevates PLLA performance to levels comparable with PVDF, while maintaining biodegradability. By coupling passive, on-demand electromechanical stimulation with the intrinsic rhythm of the beating heart, US-PLLA promotes myocardial integration, restores electrical connectivity, reduces hypertrophy, and enhances angiogenesis. Together, these findings establish US-PLLA as a degradable piezoelectric platform for electromechanically mediated cardiac repair, addressing longstanding barriers to translation.

2.6. Universal application of the HUST method

To investigate the universality of the HUST method on other polymer materials, we applied it to PCL and PC using a similar procedure. Both polymers showed significant enhancement of crystallinity after HUST processing, as confirmed by macrophotography and XRD analysis (Supplementary Fig. S21). The US-PCL exhibited a notable increase in crystallinity compared to non-US PCL, and US-PC also showed improvement. However, other polymers, such as PMMA and PVC, did not show significant crystallinity enhancement. The above phenomenon can be explained by two key factors. (1) Chain flexibility: Polymers with moderate chain flexibility (PLLA, PCL, PC) are responsive to HUST, while rigid-chain polymers (PMMA, PVC) are not; (2) Crystallizability: HUST is effective for semicrystalline polymers (PLLA, PCL) but not for amorphous polymers (PMMA). We further supplemented comparative experiments using PHBV (poly (3-hydroxybutyrate-co-3-hydroxyvalerate), a biodegradable polymer with weak intrinsic piezoelectricity. The results reveal that ultrasonically treated PHBV exhibits a distinctly higher apparent d₃₃ than untreated PHBV (Supplementary Fig. S22), further confirming that ultrasonically induced local chain alignment accounts for the improved apparent piezoelectric response. Overall, the HUST strategy might be considered a universal method for varying the crystallinity and piezoelectricity of polymer materials without changing their composition.

3. Conclusion

Polymer crystallization critically determines material performance. Here we show that high-frequency ultrasound provides a nonthermal route to control crystallization and polarization in biodegradable polymers. Ultrasound-mediated alignment of PLLA chains induced the β-form crystal and stable ferroelectric electrets, yielding piezoelectric coefficients approaching those of non-biodegradable PVDF. This effect arose from frequency-dependent molecular orientation within the solvent field rather than thermal activation. The resulting piezoelectric US-PLLA exhibited high electromechanical coupling, biocompatibility, and biodegradability, enabling real-time physiological monitoring and cardiac function restoration in vivo. Extending this approach to other polymers demonstrates its generality, establishing ultrasound-driven crystallization as a versatile platform for creating transient, implantable piezoelectric materials for next-generation bioelectronic medicine, with potential applications in cardiovascular regenerative remodeling, nerve repair, and osteochondral healing.

Ethics approval and consent to participate

All animal experiments were performed according to the protocols approved by the IACUC of the Huazhong University of Science and Technology (HUST-IACUC-2025-0029).

CRediT authorship contribution statement

Xinchang Kang: Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. Yawu Li: Conceptualization, Data curation, Formal analysis, Investigation, Software, Visualization, Writing – original draft. Ruiyue Zhao: Data curation, Formal analysis, Investigation, Software, Writing – original draft. Yi Yuan: Investigation. Qi Chen: Investigation. Pengyu Li: Investigation, Writing – review & editing. Zhengbao Yang: Supervision, Writing – review & editing. Jianglin Wang: Conceptualization, Funding acquisition, Project administration, Supervision, Writing – original draft, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

The following are the Supplementary data to this article: