Introduction

Postoperative complications following small intestine resection, such as intestinal motility disorders, ileus, and constipation1,2,3, are common and require regular monitoring for effective postoperative management4. Real-time feedback on intestinal motility at the surgical site is crucial for accurate diagnosis, appropriate medical treatment, and management of intestinal motility disorders5,6. However, traditional endoscopic screening methods are limited to deep small intestine examinations and long-term monitoring of intestinal motility7,8. Besides, the anesthesia operation can disrupt the normal intestinal motility of the patient9,10. Therefore, in awake patients, clinical intestinal examinations primarily rely on contrast-enhanced imaging technologies, including magnetic resonance imaging (MRI)11,12 and computed tomography (CT)13,14. While contrast-enhanced imaging technologies offer high-resolution imaging for monitoring intestinal bleeding and inflammation, they are limited in frequent monitoring, costly, and require well-trained clinicians to operate15,16. Alternatively, ultrasonography is one of the most used diagnostic tools in clinical practice due to its non-radiation, dynamic imaging, and convenience17,18,19,20. Recently, researchers have developed wearable ultrasound devices for long-term and continuous ultrasound monitoring of internal organs, including the heart21, stomach22, and bladder23. However, soft and complex tissues, such as intestines, have weak ultrasound reflections and uncertain positions, posing challenges for clear ultrasound imaging24,25. Currently, clinicians inject ultrasound contrast agents based on gas-filled microbubbles intravenously to achieve ultrasound contrast imaging of soft tissues26,27,28. However, these contrast agents usually burst and disappear within a few minutes in the blood, making them unsuitable for long-term ultrasound monitoring29,30. In addition, the injectable contrast agent distributes throughout all major blood vessels as blood circulates31, unsuitable for precise imaging of a specific organ or tissue segment, posing challenges for tracing the motility of the surgically treated intestine.

To achieve long-term ultrasound imaging of the surgically treated soft tissues, implantable ultrasound contrast materials were developed by incorporating rigid materials such as silicon32, metal33, or dioxide34,35 into soft materials. These rigid materials generate strong ultrasound reflections due to the large acoustic impedance difference with soft tissues36. However, rigid materials in ultrasound contrast implants raise concerns regarding softness, biodegradability, and biocompatibility, posing practical challenges37,38,39. Alternatively, gas-filled microbubbles exhibit an acoustic impedance difference from soft tissues, providing a moderate contrast in ultrasound imaging40,41. However, microbubbles also face challenges in effective ultrasound monitoring of intestines, due to their non-specific shape and scant acoustic reflectivity related to concentration. Soft acoustic metamaterials, with specific structural designs and functions, have gained significant attention in the biomedical field due to their passive nature, low Young’s modulus, and impressive biocompatibility42,43,44. Previous research has demonstrated the use of metagel sensors for continuous and wireless monitoring of physiological signals, highlighting the potential of soft acoustic metagel for implantable sensor design45,46.

In this work, we propose a biodegradable ultrasound contrast tape (BioUCT) designed for regular monitoring of small intestinal motility through ultrasound imaging, enabling early detection of postoperative complications after small intestine resection. The BioUCT consists of a thin, soft acoustic metagel that adheres robustly to the intestine with a bioadhesive hydrogel layer, facilitating easy application by clinicians as the final step of the surgery and enabling post-surgery monitoring through ultrasound imaging. The BioUCT reflects ultrasound waves with frequencies below 5 MHz very strongly (> 90%), resulting in high-contrast imaging. The thin thickness (~ 1 mm) and low Young’s modulus (~ 20 kPa) of the BioUCT facilitate easy conformal attachment to curved and soft tissues like intestines. The BioUCT enhances the brightness of a live pig’s small intestine in ultrasound images by 40 dB and can provide clear ultrasound imaging over 2 weeks after the implantation. The BioUCT can also naturally biodegrade in 12 weeks, without the need for removal surgery. Combined with existing wearable ultrasound imaging devices, the BioUCT can achieve long-term clear ultrasound imaging of soft tissues, providing an effective diagnostic tool for tracing intestinal motility and optimizing postoperative treatment.

Results

Design of the BioUCT

The design of the biodegradable ultrasound contrast tape (BioUCT) is driven by the need for continuous and high-contrast ultrasound imaging of the intestine, particularly in the long-term postoperative monitoring of intestinal motility (Supplementary Movie 1). The bottom layer of the BioUCT is composed of bioadhesive hydrogels designed for robust adhesion to the intestinal surface, ensuring secure attachment of the BioUCT and strong ultrasound reflectance during dynamic movements, as shown in Fig. 1a. The BioUCT can improve the brightness of soft tissue significantly and provide clear visibility of the small intestine, as shown in Fig. 1b. Currently, injected ultrasound contrast agents based on microbubbles are the most widely used ultrasound contrast imaging methods in clinical situations. The clinically injected agents can produce a clear image of the soft intestine in contrast imaging mode. However, the effective duration of microbubbles lasts only a few minutes after the injection (Fig. 1c, d), posing challenges for long-term postoperative monitoring that lasts for several weeks. Compared to clinically injected contrast agents, which dissipate within minutes, BioUCT maintains consistent brightness in ultrasound images throughout the examination (Fig. 1e, f), extending the effective imaging window from minutes to weeks.

Fig. 1: The design of BioUCT for ultrasound contrast imaging.
Fig. 1: The design of BioUCT for ultrasound contrast imaging.The alternative text for this image may have been generated using AI.
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a Schematic diagram of the soft BioUCT implanted on the intestine. b Ultrasound contrast imaging of the BioUCT on the small intestine. c Limited imaging time of injected contrast agent (SonoVue, Bracco). d Decreasing brightness of injected contrast agents in 8 min. e Stable imaging of BioUCT. f Constant brightness of BioUCT in 8 min. g Structures of the BioUCT. The inset microscopic image shows the zoomed-in view of periodic air cells sealed in the tough hydrogel. The scale bar is 1 mm. h Structures of the BioUCT, including air cells sealed in the tough hydrogel and bioadhesive hydrogels at the bottom layer. i Cross-linking networks of tough hydrogels and bioadhesive hydrogels. j Scanning electron microscopy (SEM) image of the cross-section of the BioUCT. The scale bar is 20 μm. k Strong ultrasound reflection of BioUCT compared to soft tissue. l Comparison of Young’s modulus and simulated ultrasound reflectance at 4 MHz of soft tissues, traditional materials, and the BioUCT. m Softness of the BioUCT in deformation. The scale bar is 10 mm.

The top-view micrographs of the BioUCT in Fig. 1g show periodical air cells sealed within the tough hydrogel. The all-hydrogel design of the BioUCT, which includes the tough PVA/CMC hydrogel and bioadhesive PAA/NHS hydrogel (Fig. 1h–j), provides softness and biocompatibility suitable for long-term implantation applications. The strong ultrasound reflection of BioUCT (Fig. 1k) is achieved by a single layer of periodic air cells sealed in tough hydrogels. Periodic air cells enhanced the equivalent acoustic impedance mismatch between the BioUCT and the surrounding soft tissues, creating a strong ultrasound reflection at the acoustic interface between the hydroperitoneum and BioUCT (Supplementary Movie 2). Compared to traditional materials, the BioUCT maintains good softness similar to soft tissues while achieving high ultrasound reflectance similar to rigid metals, as shown in Fig. 1l and Supplementary Fig. 1. The softness, strong ultrasound reflectance, and robust adhesion ability of the BioUCT make it an effective contrast imaging tool for regular and wireless monitoring of intestinal motility. In addition to the strong ultrasound contrast capability, Fig. 1m further demonstrates the flexibility of the BioUCT in various deformations, which is crucial for conformal attachment to the complex surface of the small intestine. To facilitate the use of clinicians, BioUCT can be rolled up into a shape similar to medical tape and cut as needed by clinicians.

Acoustic characterization of the BioUCT

The ultrasound reflectance of the BioUCT was evaluated through both numerical simulations and experimental tests to ensure its efficacy in enhancing ultrasound imaging. To verify the reflection performance of the BioUCT, an underwater simulation model is established, as shown in Supplementary Fig. 2. The blocking effect of the BioUCT and soft hydrogels on 4 MHz ultrasound waves in Supplementary Fig. 1 shows that periodic air cells sealed in hydrogels significantly improve the reflectance of 4 MHz ultrasound waves. The ultrasonic reflectance of the BioUCT across frequencies ranging from 1 to 10 MHz is further demonstrated in Supplementary Figs. 3–6, showing a broad frequency range with strong reflectance, suitable for various ultrasound imaging scenarios. The reflectance performance of the BioUCT is influenced by several structural parameters, including the lattice constant a (Supplementary Fig. 3), air filling ratio p = d/a (Supplementary Fig. 4), the height of air cells h (Supplementary Fig. 5), and the air cell numbers n (Supplementary Fig. 6). The lattice constant a and air filling ratio p of the BioUCT are related to the frequency of its strong reflection band. The height h and number n of air cells are related to the reflectance of the BioUCT. The ultrasound characterizations of BioUCT with different air cell designs confirm that the ultrasound reflectance of the BioUCT can be optimized for various applications. In addition, the low Young’s modulus of BioUCT makes it easy to deform. Thus, analyzing the effect of BioUCT’s deformation on its ultrasound reflection performance is essential to assess the stability of the BioUCT. In Supplementary Fig. 7, the shape and size change of air cells in BioUCT under different strain rates and bending angles were simulated. The deformed BioUCT was then placed in the underwater finite element analysis (FEA) model to simulate the impact of deformation on its ultrasound reflection performance, as shown in Supplementary Figs. 8, 9.

Considering the fabrication, stability, and ultrasound reflectance, BioUCT with lattice constant a = 0.45 mm, air filling ratio p = 0.7, and height h = 0.5 mm is designed and then fabricated by curing hydrogels in a resin mold with a defined microstructure (Supplementary Fig. 10), followed by a sealing process as described in the Methods section. The BioUCT with periodic air cells sealed in hydrogels (Supplementary Fig. 11) is soft and exhibits good conformability, as shown in Supplementary Fig. 12. The BioUCT was then tested in an underwater ultrasonic system, using an ultrasound transducer with a central frequency of around 2 MHz. The time-domain and frequency-domain characterizations of ultrasound reflected by the BioUCT showed a much larger amplitude compared to the hydrogel, verifying the strong ultrasound reflectance from periodic air cells, as shown in Fig. 2a. Compared to PVA/CMC hydrogels, the spectrum amplitude of echoes reflected by BioUCT is increased by 57 dB, resulting in 30 dB improvement in ultrasound image brightness, as shown in Fig. 2b. The BioUCT consistently produces bright and distinct images across different probe positions, as shown in Fig. 2c–e. These images assess the brightness of the BioUCT in B-mode ultrasound images at varying depths, angles, and horizontal positions. The air cells in BioUCT are sealed with tough hydrogels, maintaining stable structure and ultrasound imaging contrast even after 15 days of immersion in PBS solution, as shown in Supplementary Fig. 13.

Fig. 2: Ultrasound contrast imaging performance of the BioUCT.
Fig. 2: Ultrasound contrast imaging performance of the BioUCT.The alternative text for this image may have been generated using AI.
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a Time-domain (left image) and frequency-domain (right image) characterization of echoes reflected by the BioUCT, compared to the hydrogel. b B-mode imaging result of the BioUCT compared to the hydrogel. The scale bar is 10 mm. c–eBrightness of the BioUCT in B-mode ultrasound images at different probe positions (depth, angle, and horizontal position); Data are presented as mean ± SD. Each data point represents the mean of n independent tests (n = 3). Error bars indicate SD. The scale bar in the inset image is 1 cm. f B-mode ultrasound images of the BioUCT and time-domain signals acquired by the M-mode scanning line during the bending process. The scale bar is 5 mm. g M-mode imaging of the BioUCT (upper images) and phase monitoring waveform (bottom images) during the bending process.

In addition, the dynamic performance of the BioUCT was evaluated during the bending deformation process. The stable B-mode images of the BioUCT and time-domain signals acquired by an M-mode scanning line during the bending process are shown in Fig. 2f and Supplementary Fig. 14. During the 50% stretching process, BioUCT also maintained its stable high brightness on the B-mode ultrasound image, as shown in Supplementary Fig. 15. The M-mode imaging and phase monitoring waveform in Fig. 2g further demonstrate the BioUCT’s reliable performance under mechanical deformation, ensuring consistent imaging quality during intestinal motility.

In vitro demonstration of the BioUCT

To validate the BioUCT’s effectiveness in enhancing ultrasound imaging of soft tissues, in vitro tests were conducted to evaluate the adhesive strength, imaging performance (Supplementary Movie 3), and degradation characteristics of the BioUCT.

Stable adhesion of the BioUCT is crucial for reliable long-term monitoring, especially on the dynamic intestinal surface. Figure 3a demonstrates the BioUCT’s ability to maintain robust adhesion under high pulling forces. The BioUCT adhered to the ex vivo small intestine withstands significant mechanical stress, indicating its suitability for dynamic environments within the body (Supplementary Movie 4). The interfacial toughness between the bioadhesive hydrogel of the BioUCT and porcine small intestine remained robust within 48 hours after adhesion formation, as shown in Fig. 3b. The error bars represent the standard deviation (± SD) of weight ratio across three independent samples, ensuring the consistency of these results. To evaluate the long-term adhesion stability of BioUCT on the intestine, both ex vivo and in vivo adhesion tests were conducted in Supplementary Fig. S16 to confirm the stable bioadhesion stress of BioUCT in 15 days. The stable ultrasound imaging contrast in Supplementary Fig. S17 further verifies the long-term adhesion of the BioUCT for tracking intestinal motility.

Fig. 3: Ex vivo demonstration of the BioUCT.
Fig. 3: Ex vivo demonstration of the BioUCT.The alternative text for this image may have been generated using AI.
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a The BioUCT adhered to the ex vivo small intestine can withstand high pulling force and maintain robust adhesion to the small intestine. The scale bar is 10 mm. b Interfacial toughness between the bioadhesive hydrogel and porcine small intestine measured within 48 h after adhesion formation. Data are presented as mean ± SD. Each data point represents the mean of n independent samples (n = 3). Error bars indicate standard deviation (± SD) of the weight ratio. c Ultrasound contrast imaging of ex vivo intestine (left image). The scale bar in the ultrasound image is 2 cm. The brightness of the intestine (right image) is improved by 33 dB on the ultrasound image using BioUCT. Data are presented as mean ± SD. Each data point represents the mean of n independent tests (n = 3). Error bars indicate ± SD of the brightness. d B-mode ultrasound image (left) and an M-mode ultrasound image (right) for tracking dynamic intestinal motion in an ex vivo test. The scale bar is 5 mm. e The degradation rate of the BioUCT can be adjusted between 10% and 90% degradation in PBS solution (37 °C) within 120 days. Data are presented as mean ± SD. Each data point represents the mean of n independent tests (n = 3). Error bars indicate ± SD of the weight ratio. f Images showing the degradation process of BioUCTs with various degradation rates. The scale bar is 1 mm. g Young’s modulus of BioUCTs with different degradation rates. Data are presented as mean ± SD. Each data point represents the mean of n independent tests (n = 3). Error bars indicate the ± SD of Young’s modulus.

Evaluating the ultrasound imaging performance of the BioUCT is vital to confirm its ability to enhance the visibility of soft tissues. The BioUCT was attached to the porcine intestine and placed at a depth of 15 cm underwater to evaluate its ultrasound contrast ability, as shown in Fig. 3c. The BioUCT significantly enhances the brightness of the porcine intestine by 33 dB in ultrasound images, providing clear and distinct visualization for long-term monitoring. When conducting underwater ultrasound imaging on in vitro organs, residual gas inside the organs can cause cloud-like reflections in ultrasound images, resulting in relatively high background brightness. Despite the existence of residual gas, BioUCT significantly enhanced the brightness of the porcine intestine in ultrasound images, effectively distinguishing the contrast from gas. Furthermore, when attached to other organs, such as the porcine heart and stomach, BioUCT also obviously improved the tissues’ brightness and contrast in ultrasound images, as shown in Supplementary Fig. 18. The enhanced imaging clarity from BioUCT is crucial for accurate monitoring and diagnosis of conditions of the intestine and other organs.

The dynamic imaging capabilities of the BioUCT are further demonstrated in Fig. 3d. A M-mode scanning line is set in the B-mode image (left image of Fig. 3d) of the intestine to acquire continuous ultrasound data for processing. To simulate the peristalsis of the porcine intestine, an operator holds the intestine and swings it periodically during the measurement of the ultrasound. As the porcine intestine moved from the bottom to the top position, ultrasound data were continuously acquired and synthesized into an M-mode ultrasound image, as shown in Fig. 3d (right). The BioUCT significantly enhances the brightness of the porcine intestine in the M-mode ultrasound image. The enhanced M-mode ultrasound image of the intestine allows for tracking the dynamic motion of the intestine.

The BioUCT in this work is fabricated by biodegradable hydrogels, eliminating the need for a second surgery to remove it after use. The biodegradation weight of the BioUCT within 120 days can be adjusted from 10% to 90% (Fig. 3e), which is measured by immersing the BioUCT in PBS solution at 37°C. Images in Fig. 3f illustrate how the BioUCT gradually broke down over time, showing an adjustable degradation rate visually. The biodegradation rate of the BioUCT can be controlled by adjusting the crystallinity of the PVA/CMC hydrogel. However, the higher crystallinity of the hydrogel will also result in higher Young’s modulus, as shown in Fig. 3g. In practical applications, the crystallinity of the hydrogel used in BioUCT should be carefully determined to balance the degradation rate and Young’s modulus of the BioUCT (Supplementary Table 1).

The in vitro demonstration in Fig. 3 confirms the BioUCT’s strong adhesion, superior ultrasound imaging performance, and controlled degradation characteristics. These findings highlight BioUCT’s potential for enhancing the ultrasound imaging of soft tissues and its suitability for clinical applications in monitoring intestinal motility and other dynamic physiological processes.

Biocompatibility and biodegradability characterization

Biocompatibility and biodegradability tests were performed on the tough hydrogel with the bioadhesive layer used in BioUCT, to demonstrate the potential of BioUCT’s implantable applications. Biocompatibility ensures that the BioUCT does not induce any adverse cellular or systemic responses, while biodegradability confirms that the BioUCT can be safely broken down and absorbed by the body without the need for removal.

To evaluate the biocompatibility of the BioUCT, an in vitro analysis using human cardiac microvascular endothelial cells (HCMECS) was conducted to assess whether the implanted BioUCT affects cell viability (Supplementary Fig. 19) and metabolic activity over an extended period. The live/dead staining (green for live cells and red for dead cells) image in Fig. 4a reveals that there is no significant increase in cell death in the presence of hydrogels compared to the control. Fluorescence images of HCMECS cultured with hydrogels for 21 days showed normal cell proliferation. The ATP quantification results in Fig. 4b show a consistent level between the hydrogels and the control group over 21 days, further verifying the biocompatibility of the BioUCT.

Fig. 4: Biocompatibility and in vivo biodegradability of the BioUCT.
Fig. 4: Biocompatibility and in vivo biodegradability of the BioUCT.The alternative text for this image may have been generated using AI.
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a, b Fluorescence images of live (green)/dead (red) HCMECS with and without the BioUCT for 21 days. The scale bar is 50 μm. b The ATP quantification of HCMECS cultured with and without the BioUCT for 21 days. Data are presented as mean ± SD. Each data point represents the mean of n independent samples (n = 6). Error bars indicate the ± SD of ATP measurement. c In vivo biodegradation images of the BioUCT within 12 weeks (upper images). The scale bar is 1 cm. Masson’s trichrome staining of paraffin sections of the implant and surrounding tissues (bottom images). The scale bar is 2 mm. d Weight ratio of the BioUCT within the in vivo biodegradation process. Data are presented as mean ± SD. Each data point represents the mean of n independent samples (n = 3). Error bars indicate the ± SD of the weight ratio. e, f Results of blood count (e) and blood chemistry (f) tests over 12 weeks after the implantation of BioUCT in rats. The BioUCT shows no statistical difference compared to the control group. Data are presented as mean ± SD. Each data point represents the mean of n independent samples (n = 3). Error bars indicate the ± SD of test results. g Results of paraffin sections for H&E staining. Vital organs of rats showed no obvious abnormalities 12 weeks after implantation. The scale bar is 200 μm.

In addition, the tough hydrogel was implanted into rat models to validate its biodegradability and biocompatibility during the degradation process in vivo. Images and Masson’s trichrome staining of paraffin sections of the implant during the degradation process are presented in Fig. 4c, illustrating a gradual degradation of the tough hydrogel. The tough hydrogel implant degrades 70% of its weight within 12 weeks (Fig. 4d), eliminating the need for surgical removal. During the degradation process of tough hydrogel, the blood counts and blood chemistry values of implanted rats were measured over 12 weeks, as shown in Fig. 4e, f and Supplementary Fig. 20. The blood count and blood chemistry values show no obvious statistical differences between the tough hydrogel and control groups, confirming the biocompatibility of the BioUCT. Furthermore, histological analysis of vital organs, including the heart, liver, spleen, lungs, and kidneys, was performed using hematoxylin and eosin (H&E) staining, as shown in Fig. 4g. Compared to the control group, no observable abnormalities appeared in rat’s vital organs 12 weeks after the tough hydrogel implantation.

The comprehensive evaluation of BioUCT’s biocompatibility and biodegradability through both in vitro and in vivo studies confirms its safety and effectiveness for implantable applications. The lack of cytotoxic effects, absence of adverse systemic responses, and 70% biodegradation within 12 weeks highlight BioUCT as a promising implant for regular and long-term monitoring of postoperative intestinal motility.

Tracing intestinal motility in vivo

The effectiveness of BioUCT in the postoperative regular monitoring of intestinal motility was also validated in live pig models (Supplementary Movie 5). The BioUCT was implanted on the small intestine of a live pig (Fig. 5a) to provide high-contrast ultrasound imaging for postoperative regular and long-term monitoring of intestinal motility. Following the implantation, blood count and blood chemistry tests were performed on the pig over 10 weeks to monitor any potential negative effects of BioUCT, as shown in Fig. 5b. Blood counts and chemistry values, including the white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), platelet (PLT), total protein (TP), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (CREA), blood urea nitrogen/CREA ratio (BUN/CREA) and glucose (GLU), showed no significant abnormality during the 10 weeks of implantation, further confirming the biocompatibility of BioUCT in the live pig model.

Fig. 5: Tracing intestinal motility by BioUCT in vivo.
Fig. 5: Tracing intestinal motility by BioUCT in vivo.The alternative text for this image may have been generated using AI.
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a Implanting the BioUCT on the small intestine of a live pig. b Results of blood count (e) and blood chemistry (f) tests within 10 weeks after the implantation of BioUCT in a live pig. c Image of a live pig’s small intestine before and after the implantation of the BioUCT. The scale bar is 10 mm. d B-mode ultrasound image of the pig’s small intestine before the implantation (left), compared to images at day 1 (middle) and day 15 (right) after the implantation of the BioUCT. The scale bar is 10 mm. e The BioUCT enhanced the brightness of the small intestine after the implantation; n  =  3 independent tests. f B-mode ultrasound imaging with a time interval of 15 s. The scale bar is 20 mm. g The placement of the M-mode scanning line. The scale bar is 10 mm. h Time-domain waveform of echoes reflected by the BioUCT. i M-mode ultrasound imaging of the BioUCT for tracing intestinal motility. The amplitude of the intestinal motility increases from 3.13 mm to 7.59 mm after taking Motilium.

To quantify the ultrasound contrast imaging performance of the BioUCT, ultrasound imaging was performed on the live pig’s small intestine before and after the implantation of BioUCT (Fig. 5c). Due to the similar acoustic impedance between the intestine and surrounding tissue fluid, the brightness of the soft small intestine in the ultrasound image is quite low (~ 5 dB), as shown in Fig. 5d. In contrast, after the implantation of BioUCT, the brightness of small intestine on B-mode ultrasound images improved to nearly 45 dB. The BioUCT maintains ultrasound contrast imaging ability on the small intestine for 15 days, enabling long-term monitoring of intestinal motility for weeks, as shown in Fig. 5e. To observe intestinal peristalsis using ultrasound images, two BioUCTs were implanted next to each other on the small intestine of a live pig. Fifteen days post-implantation, the active intestinal motility of the pig can still be visually assessed according to the separation and closeness of BioUCTs in ultrasound images in Fig. 5f. The motility of the active intestinal motility in Fig. 5f is very different from the B-mode ultrasound images of the pig’s intestine at the quiet state in Supplementary Fig. 21. Furthermore, Supplementary Fig. 22 further demonstrates the potential of BioUCT in enhancing B-mode ultrasound imaging of a live pig’s stomach.

To further quantify the intestinal motility, an M-mode scanning line was set in the B-mode ultrasound image in Fig. 5g to acquire the time domain waveform of echoes reflected by the BioUCT. According to the time-domain data in Fig. 5h, the ultrasound echoes reflected by BioUCT are significantly stronger than surrounding tissues. Based on the ultrasound data collected from the M-mode scanning line, the M-mode ultrasound image was synthesized to demonstrate the motility of the small intestine, as shown in Fig. 5i. The brightness of the BioUCT is also significantly higher than that of the surrounding tissue in M-mode ultrasound images. By tracking high-brightness locations in the M-mode ultrasound image, the motility of the intestine can be further quantified, as shown in Supplementary Fig. 23. Before taking Motilium, the pig’s small intestine was in a quiet state with a detected peristaltic amplitude of 3.13 mm. However, following the administration of Motilium, the small intestine changed into an active state with a detected peristaltic amplitude of 7.59 mm, indicating an obvious increase in the amplitude of the intestinal motility. Combined with clinical ultrasound imagers, the BioUCT can be used to assess intestinal motility during clinical treatment and post-operation management.

By providing high-contrast ultrasound images and capturing dynamic movements of the intestine, BioUCT facilitates postoperative regular and wireless tracking of intestinal motility, which is particularly valuable in postoperative care. The BioUCT represents a significant step forward in the management of intestinal motility disorders, offering a practical and effective tool for clinicians.

Discussion

Postoperative regular monitoring of intestinal motility is essential for detecting complications following small intestine resection. Although ultrasound imaging is an ideal tool for continuous monitoring of internal organs due to its radiation-free, low-cost, and wireless monitoring advantages, the soft intestine with low brightness on ultrasound images is still a challenge for ultrasound monitoring. In this work, we propose a biodegradable ultrasound contrast tape (BioUCT) that can robustly adhere to the intestinal surface and provide high-contrast ultrasound images. The BioUCT naturally degrades within 12 weeks after implantation and causes no significant negative impact on the normal physiological functions during this degradation process, eliminating the need for surgical removal. Besides, the BioUCT with high ultrasound reflection shows high brightness in ultrasound images, enabling postoperative regular and wireless ultrasound monitoring of the intestine. The bioadhesive, biocompatible, and biodegradable BioUCT improves the brightness of the small intestine in a live pig by 40 dB, available for postoperative monitoring of intestinal motility.

Compared to existing ultrasound contrast agents in Fig. 1c, d and Supplementary Fig. 24, BioUCT extends the effective time of ultrasound contrast imaging from several minutes to 15 days, meeting clinical needs for long-term and precise ultrasound imaging for internal soft tissues. The acoustic scattering properties of BioUCT’s air cells provide high imaging contrast in both B-mode and contrast-mode ultrasound images, as shown in Supplementary Fig. 25. Therefore, BioUCT can also be combined with other existing ultrasound contrast agents to achieve more ultrasound monitoring functions. Unlike ultrasound imaging implants with metal materials wrapped in soft materials (Supplementary Table 2), BioUCT consists of periodic air cells sealed with hydrogels. The all-hydrogel design of the BioUCT provides softness, conformal attachment to the complex surface of the small intestine, reduced risk of detachment, and minimal mechanical damage to surrounding tissues, enabling stable long-term ultrasound imaging monitoring of the small intestine (Supplementary Fig. 26).

Although the BioUCT in this work primarily focuses on tracing small intestinal motility, the application field of the BioUCT can be further explored for ultrasound contrast imaging of other organs, such as the stomach and heart. However, due to the inability of ultrasound waves to penetrate rigid bones, the BioUCT is not suitable for imaging tissues beneath the bone. Besides, the BioUCT manufactured in this study has a cutoff frequency of around 5.5 MHz. Although we have proposed designs for BioUCT with higher cutoff frequencies, the actual fabrication of the micro air cells was limited by the 3D printing precision of the mold. In addition, by combining with stimulus-responsive hydrogels33, the BioUCT proposed in this study can be used for monitoring more physiological environments through ultrasound imaging. In the future, the BioUCT can be integrated with wearable ultrasound devices22,47,48, achieving long-term continuous monitoring of soft organs for weeks.

Methods

Ethical Statement

All animal experiments were conducted by protocols approved by the Committee on Animal Care of Hubei Yizhicheng Biotechnology Co., Ltd. (Approval No. WDRM-202303001).

Numerical simulation

The underwater acoustic pressure field and reflectance of the BioUCT are investigated in COMSOL Multiphysics (Ver. 5.4) based on the finite element method. The type of the mesh element is free triangular, and the maximum size is 0.03 mm (< λ/5) in the simulation. The hyperelastic model is utilized to simulate the deformation of the BioUCT. The detailed simulation model and boundary condition settings are shown in Supplementary Fig. 2.

Preparation of tough hydrogel

Polyvinyl alcohol (PVA) / carboxymethyl chitosan (CMC) hydrogels were synthesized by ionic crosslinking and freezing-thawing methods to synthesize the tough hydrogel. Crystalline domains were used to form a hydrogel crosslinked in the Polyvinyl alcohol (PVA) network. Aluminum chloride solution was prepared for the tough hydrogel to provide the aluminum ion crosslinked with carboxymethyl chitosan.

Preparation of bioadhesive hydrogel

The bioadhesive hydrogel was synthesized by the PVA, poly(acrylic acid) grafted with N-hydroxysuccinimide ester (PAA-NHS), and chitosan. To prepare a bioadhesive hydrogel, we dissolved 5% (w/w) PVA, 20% (w/w) acrylic acid, 1% (w/w) chitosan, 2% (w/w) AAc-NHS ester, 0.1% (w/w) gelMA, and 0.2% (w/w) α-ketoglutaric acid in deionized water. The mixture was poured into a glass mold with a spacer and cured in an ultraviolet light (UV) chamber (365 nm) for 30 min. The bioadhesive hydrogel was then further dried under nitrogen flow to prepare the bioadhesive hydrogel.

Fabrication of the BioUCT

The BioUCT is realized by a synergistic combination of 4 distinct functional layers, as shown in Fig. 1h. An air-hydrogel layer with strong ultrasound reflection is sealed by the top sealing layer and bottom sealing layer, forming the metagel design of the BioUCT. A bioadhesive layer is then attached to the bottom of the metagel. To fabricate the air-hydrogel layer consisting of a single layer of periodic air cells, a resin mold with a single layer of periodic straight columns was designed and printed using a 3D printer (NanoArch S140, BMF Precision Material Technology, Inc.). The hydrogel sample with open channels is fabricated by pouring the pregel solution into the mold and crosslinking the pregel solution. Thereafter, the hydrogel sample with open channels is carefully separated from the mold. To seal the air-hydrogel layer with tough hydrogels, the hydrogel sample with open channels is packaged with a spin-coated 200 µm thick pregel solution and immersed in PBS solutions for at least 1 day to reach an equilibrium swollen state (Supplementary Fig. 27). To combine the metagel with the bioadhesive layer to form the BioUCT, the metagel was assembled with the bioadhesive hydrogel layer and sealed in a mold to apply compression, typically for 5–30 s.

Waterproof coating on tough hydrogels

For enhanced waterproofing, a hydrophobic STA/EtOAc coating can be applied to the surfaces of the air-hydrogel structure before sealing (Supplementary Fig. 28). To prepare the BioUCT with a waterproof coating, the demolded hydrogel sample with open channels was pre-treated by plasma for 5 s and immediately immersed in 0.5 M STA/EtOAc solution for 1 min. After these processes, the hydrogel sample was dried at room temperature for 2 min to remove the EtOAc. The hydrogel layer used for sealing air columns was first treated by the STA solution to form an STA coating. Last, a small amount of pregel was applied on the area where the two parts of the hydrogel come into contact with each other to fabricate the BioUCT.

Regulation of the hydrogel’s biodegradation rate

To regulate the biodegradation rate of the tough PVA/CMC hydrogel, the crystallinity of the tough hydrogel was adjusted. Decreasing the concentration of CMC in the tough hydrogel from 2 wt% to 1 wt% can slightly reduce the crystallinity and Young’s modulus to accelerate the degradation. To significantly improve the crystallinity of the tough hydrogel and delay the degradation rate, the freeze-thawed PVA/CMC hydrogel was dried in an incubator at 37 °C for 2 h and then annealed at 100 °C for 90 min.

In vitro biodegradation

In vitro biodegradation test of the tough hydrogel was carried out using enzymatic degradation media as described. The enzymatic biodegradation medium was prepared by adding 5 mg collagenase and 5 mg lysozyme to 100 mL of DPBS. The sterilized hydrogel was cut into small samples (of width 10 mm and length 10 mm) and accurately weighed. Each sample was then immersed in 15 ml of the enzymatic medium within a centrifuge tube and incubated at 37 °C with shaking at 60 rpm. At each interval, the hydrogel was removed from the incubation medium, exhaustively washed with deionized water, and lyophilized. Weight loss was determined as the percentage ratio of the mass of the lyophilized sample at each time interval, normalized by the dry mass of the original lyophilized sample.

Mechanical test

To measure Young’s modulus, the dogbone-shaped sample had the dimensions at an as-prepared state with a width of 5 mm, a thickness of 0.8 mm, and a gauge length of 10 mm. was tested on a mechanical testing machine (RGM-6005, REGER) with a 20 N load cell at a strain rate of 0.01 s–1. A nominal stress–stretch curve was plotted for each specimen, and Young’s modulus was identified by the initial slope.

To measure adhesive energy, a bioadhesive hydrogel was adhered to the porcine intestine and tested by the 180-degree peel test with a mechanical testing machine (RGM-6005, REGER). All tests were conducted with a constant tensile speed of 50 mm min−1.

Ultrasound system for the wireless monitoring of the BioUCT

Ultrasound imaging systems are used in this work to wirelessly monitor the implanted BioUCT and provide continuous ultrasound images for analysis. Typically, a portable ultrasound imager (S9 pro, SonoScape) equipped with a convex array probe (3C-A) was used to enable various ultrasound imaging of the BioUCT. When using an M-mode scanning line for data acquisition, an integrated ultrasound system (128 piezoelectric elements with data acquisition, tailored by Stork Healthcare Co., Ltd) was employed to obtain the raw RF ultrasound data. MATLAB R2024a (Ver. 1.0.0.1) was used for ultrasonic data analysis. Ultrasound images were processed in Python (Ver. 3.11). Plots in this work were generated using OriginPro software (version 10.1) and subsequently reorganized in Adobe Illustrator (version 27.2).

Live/dead assay of in vitro cells

Human cardiac microvascular endothelial cells (HCMECS, WN-10341, Warner Biology) were cultured and removed from the flask using enzymatic digestion (trypsin/EDTA). The cell suspension was then centrifuged at 1000 rpm for 5 min. A total of 5 × 105 cells was inoculated in each well of a 6-well plate and incubated in a CO2 incubator (5% CO2 at 37 °C, > 90% humidity) for 24 h to allow the cells to adhere to the wall. Subsequently, the medium was removed, and 2 mL of the sample leaching solution from each group was added to the 6-well plate, and incubation continued for 48 h. Following two washes with PBS buffer, 0.5 mL of LIVE/DEAD staining solution (KTA1001, Abbkine, China) was added to each well and incubated for 15 min at 37 °C in the dark. Following two further washes with PBS, the cells were placed under a fluorescent microscope and photographed. The live-cell area was quantified using Image J (Ver. 1.51j).

To assess the adenosine triphosphate (ATP) content, 1 × 10^4 cells were added to each well of a 96-well plate. Following a washing step with phosphate-buffered saline (PBS), the ATP levels were quantified using the CellTiter-Glo® Luminescent Cell Viability Assay (Promega). ATP is a key energy source for various biological processes in living cells, and thus, ATP levels indicate the number of metabolically active cells present.

Ex vivo functions assessment of BioUCT

The BioUCTs are attached to the porcine heart, stomach, and intestine, respectively, to verify the BioUCT’s contrast imaging capability. The fresh porcine heart, stomach, and intestine are obtained from the local slaughterhouse. To evaluate the effectiveness of BioUCT in enhancing organ ultrasound imaging, the porcine heart, stomach, and intestine with BioUCT attached were placed in a water tank. A portable ultrasound imaging device was used to image these organs underwater. To closely simulate the actual imaging conditions of BioUCT within the animal, a piece of pork with the skin was placed between the ultrasound probe and the organs to mimic the animal’s skin. The movement of the organs during the ex vivo test is achieved by pressing the underwater organs by hand.

In vivo function assessment of BioUCT

Female Bama minipigs weighing 30–40 kg were anesthetized, and abdominal surgery was performed to attach BioUCT to the pig’s small intestine. The abdomen was then closed with sutures. The pigs were re-anesthetized on 1 day and 15 days post-implantation for regular monitoring of the BioUCT on the small intestine using an ultrasound imaging device. To significantly change the intestinal motility, the minipig is anesthetized after a 12-hour fasting period, followed by the administration of domperidone (20 mg, Xian Janssen Pharmaceutical Ltd.) via the gastric gavage. The intestinal motility was monitored using the M-mode scanning line before and after the administration of domperidone. During the implantation of the BioUCT, blood counts and blood chemistry values of the minipig were monitored for 10 weeks.

The procedure for implanting BioUCT on the stomach is similar to that for the small intestine, involving an abdominal surgery for implantation and imaging with a portable ultrasound device post-implantation.

In vivo biodegradation

A subcutaneous transplantation model was employed to assess the degradation of tough hydrogel in vivo. Hydrogel samples were cut into 1 cm × 1 cm cubes and accurately weighed. The samples were then sterilized in 75% ethanol for 15 min and washed three times with DPBS. Following sterilization and preparation of the skin on the back of the rats, an incision of approximately 2 cm in length was made along the midline. The prepared tough hydrogel was then placed under the skin and sutured. The surgical incision was reopened at 3 days, 1 week, 2 weeks, 4 weeks, 8 weeks, and 12 weeks postoperatively, and the residual hydrogel was removed and accurately weighed after photographs were taken. Three replicates were established for each time point, and the ratio of net hydrogel weight to initial weight was calculated. Masson staining was used to evaluate the effect of the implant on the surrounding tissue after implantation. First, deparaffinize the tissue sections and rehydrate them. Stain the sections with hematoxylin to color the nuclei, then differentiate and rinse. Next, apply scarlet-acid fuchsin to stain cytoplasm and muscle, followed by aniline blue to stain collagen fibers. Dehydrate, clear, and mount the sections, and then view the results under a microscope (CX40, SOPTOP, China).

In vivo biocompatibility

A total of 4 mL of blood was collected from each group of rats by the cardiac blood collection method. 2 mL of blood was placed in EDTA anticoagulation tubes for the determination of blood routine tests using a fully automated hematology analyzer (BC-5000Vet, Mindray, China). The remaining 2 mL of blood was placed in heparin anticoagulant tubes and centrifuged at 3000 rpm for 15 min at 2–8 °C within 30 minutes of specimen collection. The supernatant was then analyzed for blood biochemistry (liver and kidney functions) in a biochemical analyzer (Chemray 800, Rayto Biotech, China). Following the collection of blood samples, tissues from the heart, liver, spleen, lungs, and kidneys were obtained from each group of rats and fixed in 4% paraformaldehyde. The sections were dewaxed and rehydrated in degraded ethanol, and then the sections were washed for 1 min before staining with hematoxylin for 5 min. Subsequently, the sections were differentiated with hydrochloric acid alcohol (0.8% to 1%) and rinsed in tap water for 1 to 2 min. The sections were then stained with eosin solution for 1-2 s and dehydrated. Finally, they were immersed in xylene and sealed for microscopic examination (CX40, SOPTOP, China).

Statistics and reproducibility

The representative SEM image in Fig. 1j is from three independent tests with similar results using a Quanta 200 ESEM (FEI, USA). Representative histological images in Fig. 4c, g are from three independent tests with similar results. The blood count, blood chemistry results in rats, and ATP content data are collected from independent biological samples, and no data are excluded. Statistical analyses were performed using unpaired two-tailed Student’s t tests for comparisons between two groups and one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for comparisons among three or more groups. A p-value < 0.05 was considered statistically significant. “n.s.” in the figures denotes “not significant”.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.