Oxygen-defect bismuth oxychloride nanosheets for ultrasonic cavitation effect enhanced sonodynamic and second near-infrared photo-induced therapy of breast cancer.

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

Semiconducting polymer nanoprodrugs enable tumor-specific therapy via sono-activatable ferroptosis.

Ferroptosis, a recently identified form of cell death, holds promise for cancer therapy, but concerns persist regarding its uncontrolled actions and potential side effects. Here, we present a semiconducting polymer nanoprodrug (SPNpro) featuring an innovative ferroptosis prodrug (DHU-CBA7) to induce sono-activatable ferroptosis for tumor-specific therapy. DHU-CBA7 prodrug incorporate methylene blue, ferrocene and urea bond, which can selectively and specifically respond to singlet oxygen (1O2) to turn on ferroptosis action via rapidly cleaving the urea bonds. DHU-CBA7 prodrug and a semiconducting polymer are self-assembled with an amphiphilic polymer to construct SPNpro. Ultrasound irradiation of SPNpro leads to the production of 1O2 via sonodynamic therapy (SDT) of the semiconducting polymer, and the generated 1O2 activated DHU-CBA7 prodrug to achieve sono-activatable ferroptosis. Consequently, SPNpro combine SDT with the controlled ferroptosis to effectively cure 4T1 tumors covered by 2-cm tissue with a tumor inhibition efficacy as high as 100 %, and also completely restrain tumor metastases. This study introduces a novel sono-activatable prodrug strategy for regulating ferroptosis, allowing for precise cancer therapy.

Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Bioactive Nanoliposomes for Enhanced Sonodynamic-Triggered Disulfidptosis-Like Cancer Cell Death via Lipid Peroxidation.

Introduction: Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death. Methods: Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed. Results: SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo. Conclusion: SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.

A review of sonodynamic therapy for brain tumors.

OBJECTIVE: Sonodynamic therapy (SDT) is gaining attention as a promising new noninvasive brain tumor treatment that targets and selectively kills tumor cells, with limited side effects. This review examines the mechanisms of SDT and ongoing clinical trials looking at optimization of sonication parameters for potential treatment of glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). The results in the first patient with recurrent GBM treated at the Mayo Clinic are briefly discussed. METHODS: The authors of this literature review used electronic databases including PubMed, EMBASE, and OVID. Articles reporting relevant preclinical and clinical trials were identified by searching for text words/phrases and MeSH terms, including the following: "sonodynamic therapy," "SDT," "focused ultrasound," "5-ALA," "ALA," "brain tumors," "diffuse pontine glioma," "glioblastoma," and "high grade glioma." RESULTS: Preclinical and clinical trials investigating the specific use of SDT in brain tumors were reviewed. In preclinical models of high-grade glioma and GBM, SDT has shown evidence of targeted tumor cell death via the production of reactive oxygen species. Emerging clinical trial results within recurrent GBM and DIPG show evidence of successful treatment response, with minimal side effects experienced by recruited patients. So far, SDT has been shown to be a promising noninvasive cancer treatment that is well tolerated by patients. The authors present pilot data suggesting good radiological response of GBM to a single SDT treatment, with unpublished observation of a lack of off-target effects even after multiple (monthly) sonication outpatient treatments. The scope of the clinical trials of SDT is to investigate whether it can be the means by which the fatal diagnosis of GBM or DIPG is converted into that of a chronic, treatable disease. CONCLUSIONS: SDT is safe, repeatable, and better tolerated than both chemotherapy and radiotherapy. It has been shown to have an effect in human cancer therapy, but more clinical trials are needed to establish standardized protocols for sonosensitizer delivery, treatment parameters, and combination therapies. The most appropriate timing of treatment also remains to be determined-whether to prevent recurrence in the postoperative period, or as a salvage option in patients with recurrent GBM for which redo surgery is inappropriate. It is hoped that SDT will also be developed for a wider spectrum of clinical indications, such as metastases, meningioma, and low-grade glioma. Further clinical trials are in preparation.

Real-time mapping of photo-sono therapy induced cavitation using Doppler optical coherence tomography.

Photo-sono therapy (PST) is an innovative anti-vascular approach based on cavitation-induced spallation. Currently, passive cavitation detection (PCD) is the prevalent technique for cavitation monitoring during treatment. However, the limitations of PCD are the lack of spatial information of bubbles and the difficulty of integration with the PST system. To address this, we proposed a new, to the best of our knowledge, cavitation mapping method that integrates Doppler optical coherence tomography (OCT) with PST to visualize bubble dynamics in real time. The feasibility of the proposed system has been confirmed through experiments on vascular-mimicking phantoms and in vivo rabbit ear vessels, and the results are compared to high-speed camera observations and PCD data. The findings demonstrate that Doppler OCT effectively maps cavitation in real time and holds promise for guiding PST treatments and other cavitation-related clinical applications.

Ultrasonic neuromodulation as a new therapy for spasticity in an animal model of spastic cerebral palsy.

PURPOSE: This study aimed to evaluate a new therapeutic option for the spasticity using ultrasound neuromodulation in an animal model of spastic cerebral palsy. METHODS: Thirty-two adult male Wistar rats were randomly distributed in: negative control (NC); positive control (PC); untreated model (UTM); and treated model (TM). Rats in the control groups received sham surgery, and rats in the model groups received the spastic cerebral palsy model surgery. The rats' motor functions were evaluated by the Rotarod and CatWalk tests before and after surgery. PC and TM groups underwent ultrasonic neuromodulation by a physiotherapeutic ultrasound (intensity 0.1 W/cm2, at 1 MHz) continuous mode for 5 seconds, for seven days. RESULTS: Twelve rats showed a spastic pattern (UTM = 6 and TM = 6), motor limitations (UTM = 6 and TM = 6), and ten had difficulty feeding (UTM = 5 and TM = 5). One UTM group rat could not recover its preoperative latency time, while the other rats in the model groups did. The speed at which the limbs swung reduced after surgery and increased in subsequent assessments, demonstrating greater instability and a deficit in locomotion balance. CONCLUSIONS: Results were not yet sufficient to assert ultrasound neuromodulation as a possible therapy for spasticity in spastic cerebral palsy in the parameters used, and more studies are necessary.

Enhancing sonothrombolysis outcomes with dual-frequency ultrasound: Insights from an in silico microbubble dynamics study.

Sonothrombolysis is a technique that employs the ultrasound waves to break down the clot. Recent studies have demonstrated significant improvement in the treatment efficacy when combining two ultrasound waves of different frequencies. Nevertheless, the findings remain conflicted on the ideal frequency pairing that leads to an optimal treatment outcome. Existing experimental studies are constrained by the limited range of frequencies that can be investigated, while numerical studies are typically confined to spherical microbubble dynamics, thereby restricting the scope of the analysis. To overcome this, the present study investigated the microbubble dynamics caused by the different combinations of ultrasound frequencies. This was carried out using computational modelling as it enables the visualisation of the microbubble behaviour, which is difficult in experimental studies due to the opacity of blood. The results showed that the pairings of two ultrasound waves with low frequencies generally produced stronger cavitation and higher flow-induced shear stress on the clot surface. However, one should avoid the frequency pairings that are integer multipliers of each other, i.e., frequency ratio of 1/3, 1/2 and 2, as they led to resultant wave with low pressure amplitude that weakened the cavitation. At 0.5 + 0.85 MHz, the microbubble caused the highest shear stress of 60.5 kPa, due to its large translational distance towards the clot. Although the pressure threshold for inertial cavitation was reduced using dual-frequency ultrasound, the impact of the high-speed jet can only be realised when the microbubble travelled close to the clot. The results obtained from the present study provide groundwork for deeper understanding on the microbubble dynamics during dual-frequency sonothrombolysis, which is of paramount importance for its optimisations and the subsequent clinical translation.

[Classification and Application of Ultrasound-Responsive Nanomaterials in Anti-Inflammatory Therapy]. / è¶ å£°å“åº”åž‹çº³ç±³ææ–™åœ¨æŠ—ç‚Žæ²»ç–—ä¸­çš„åˆ†ç±»ä¸Žåº”ç”¨.

Ultrasound, a high-frequency mechanical wave with excellent tissue penetration, has been widely applied in medical diagnostic imaging. Furthermore, it has been reported that ultrasound has broad prospects for extensive applications in the field of disease treatment in recent years due to its non-invasiveness and high efficiency. Ultrasound-responsive nanomaterials have the unique advantages of a small size and a high reactivity. Such materials have the capability for precision control of drug release under ultrasound stimulation, which provides a new approach to enhancing the efficiency of drug therapy. Therefore, these materials have attracted the attention of a wide range of scholars. Inflammation is a defensive response produced by organisms to deal with injuries. However, excessive inflammatory response may lead to various tissue damages in organisms and even endanger patients' lives. Many studies have demonstrated that limiting the inflammatory response using ultrasound-responsive nanomaterials is a viable way of treating diseases. Currently, there are still challenges in the application of ultrasound-responsive nanomaterials in anti-inflammatory therapy. The design and synthesis process of nanomaterials is complicated, and further verification of the biocompatibility and safety of these materials is needed. Therefore, in this review, we summarized and classified common ultrasound-responsive nanomaterials in the field of anti-inflammation and systematically introduced the properties of different nanomaterials. In addition, the anti-inflammatory applications of ultrasound-responsive nanomaterials in various diseases, such as bone diseases, skin and muscle diseases, autoimmune diseases, and respiratory diseases, are also described in detail. It is expected that this review will provide insights for further research and clinical applications in the realms of precision treatment, targeted drug delivery, and clinical trial validation of ultrasound-responsive nanomaterials used in anti-inflammatory therapies.

[Salphen-Based Fe-N2O2@C Nanomaterial Applied in Synergistic Sonodynamic and Chemodynamic Therapy of Tumors]. / 基于Salphen结构的Fe-N2O2@C材料用于声动力协同化学动力治疗肿瘤.

Objective: To synthesize a Salphen-based Fe-N2O2@C material with high peroxidase (POD)-mimicking activity and sonosensitivity for the synergistic sonodynamic (SDT) and chemodynamic (CDT) therapy of tumors. Methods: Fe-N2O2 was synthesized via the hydrothermal method, and Fe-N2O2@C was prepared by incorporating a ketjen black substrate. The morphology, structure, composition, enzyme mimic activity for reactive oxygen species (ROS) production, and sonosensitivity of the material were characterized. The ability and mechanism of Fe-N2O2@C to perform synergistic SDT and CDT killing of 4T1 mouse breast cancer cells were explored through in vitro experiments. The in vivo tumor-killing ability of Fe-N2O2@C combined with ultrasound irradiation was investigated using a subcutaneous 4T1 tumor-bearing mouse model. Results: FFe-N2O2 and Fe-N2O2@C were both irregularly shaped nanospheres with average particle sizes of 25.9 nm and 36.2 nm, respectively. XRD, FTIR, and XPS analyses confirmed that both Fe-N2O2 and Fe-N2O2@C possessed a Salphen covalent organic framework structure with M-N2O2 coordination, and the ketjen black loading had no significant impact on this structure. Compared to Fe-N2O2, Fe-N2O2@C exhibited high POD-mimicking activity (with K m reduced from 19.32 to 5.82 mmol/L and v max increased from 2.51×10-8 to 8.92×10-8 mol/[L·s]) and sonosensitivity. Fe-N2O2@C in combination with ultrasound irradiation could produce a large amount of ROS within cells and a subsequent significant decrease in mitochondrial membrane potential, thereby inducing TEM-observable mitochondrial damage and causing cell apoptosis and death. In addition, in vivo experiments showed that Fe-N2O2@C in combination with ultrasound irradiation could effectively inhibit tumor growth in a 4T1 subcutaneous tumor-bearing mouse model without significant in vivo toxicity. Conclusion: In this study, we prepared a Salphen-based Fe-N2O2@C material with good biocompatibility, which can be used in combination with ultrasound irradiation to achieve SDT and CDT synergistic killing of tumor cells and inhibit tumor growth. This Salphen-based Fe-N2O2@C nanomaterial shows promising potential for multimodal tumor therapy.

Patient satisfaction following treatment with micro-focused ultrasound with visualization: A retrospective cross-sectional study.

BACKGROUND: There has been increased public interest in noninvasive skin tightening procedures that produce the best possible cosmetic outcomes. Micro-focused ultrasound with visualization (MFU-V) is a secure, efficient method of treating skin laxity approved by the FDA. Few studies have assessed patient satisfaction following MFU-V. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted between January 2022 and 2023. After obtaining the author's permission, a previously examined and published questionnaire was used to contact all participants (n = 98) who had received MFU-V therapy in a private clinic in Riyadh, Saudi Arabia, between 2016 and 2020 via phone interview. RESULTS: All 98 patients undergoing MFU-V were female. About two-thirds indicated they were satisfied or very satisfied with the results. Those receiving treatment around the eye and submentum reported lower satisfaction levels than those receiving therapy in other regions. The number of treatment locations and satisfaction were positively correlated. Patients treated by consultants rather than laser experts reported much higher satisfaction levels. Satisfaction and the amount of time for improvement to occur following treatment were correlated statistically. Pain and tingling were the most frequent adverse effects the respondents reported, followed by skin redness and swelling; however, adverse effects were not connected with satisfaction. Cost (78.6%) was cited as the main deterrent to seeking treatment again. CONCLUSION: MFU-V, an FDA-approved procedure, has proven effective and safe for treating facial and neck skin laxity. When patients are carefully selected and physicians properly trained, higher satisfaction is achieved.

Recent Progress in Photothermal, Photodynamic and Sonodynamic Cancer Therapy: Through the cGAS-STING Pathway to Efficacy-Enhancing Strategies.

Photothermal, photodynamic and sonodynamic cancer therapies offer opportunities for precise tumor ablation and reduce side effects. The cyclic guanylate adenylate synthase-stimulator of interferon genes (cGAS-STING) pathway has been considered a potential target to stimulate the immune system in patients and achieve a sustained immune response. Combining photothermal, photodynamic and sonodynamic therapies with cGAS-STING agonists represents a newly developed cancer treatment demonstrating noticeable innovation in its impact on the immune system. Recent reviews have concentrated on diverse materials and their function in cancer therapy. In this review, we focus on the molecular mechanism of photothermal, photodynamic and sonodynamic cancer therapies and the connected role of cGAS-STING agonists in treating cancer.

Effect of the low-intensity pulsed ultrasound therapy on healing of Achilles tendinopathy in a rat model.

OBJECTIVE:  This study aimed to investigate the effect of the low-intensity pulsed ultrasound (LIPUS) on the healing of Achilles tendinopathy in a rat model induced by type 1 collagenase. METHODS:  The study was conducted on 144 Achilles tendons of 72 Wistar albino female rats with typical activity and weighing 300-350 g. The model of Achilles tendinopathy was created by injecting type 1 collagenase. According to the sampling time, 4 groups served as the control group, while 8 groups received treatment at varying periods. Low-intensity pulsed ultrasound therapy was initiated in 8 groups at 1, 7, and 15 days. Treatment was extended for 1 and 2 weeks. Achilles tendons were removed from the treatment and control groups on the 15th, 21st, 30th, and 45th days for biomechanical and pathologic examination. RESULTS:  Compared to the control groups, LIPUS treatment administered in the first days of the proliferation phase increased tensile strength by approximately 30%, modulus of elasticity by approximately 53%, fibrillar appearance by 53%, and inflammation by 53%-33% in a shorter time. It was also demonstrated that starting treatment in the first days of the proliferation phase resulted in comparable success even with 1-week treatment compared to 2-week treatment. CONCLUSION:  Low-intensity pulsed ultrasound therapy can provide positive results in managing Achilles tendinopathy in the rat model. Its capacity to shorten recuperation time has piqued the interest of conservative treatment approaches. As a result, more clinical research is required. Cite this article as: Kurtulmus T, Çelebi ME, Bektas E, Arican ÇD, Kucukyildirim BO, Demirkol M. Effect of the low-intensity pulsed ultrasound therapy on healing of Achilles tendinopathy in a rat model. Acta Orthop Traumatol Turc., 2024;58(2):102-109.

In-Situ Grown Nanocrystal TiO2 on 2D Ti3C2 Nanosheets with Anti-Tumor Activity from Photo-Sonodynamic Treatment and Immunology.

Introduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo. Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth. Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment. Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.

Effect of low-intensity pulsed ultrasound on postoperative rehabilitation of rotator cuff tears: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tears are a common shoulder injury that significantly impacts patients' daily lives and work abilities. Although surgical treatment methods for rotator cuff tears have been continuously improved with advances in medical technology, postoperative rehabilitation remains challenging. Therefore, finding effective rehabilitation treatments is crucial for improving patient prognosis and enhancing quality of life. This study will aim to systematically evaluate the impact of low-intensity pulsed ultrasound (LIPUS) on postoperative rehabilitation of rotator cuff tears, comprehensively assessing the efficacy and safety of LIPUS in postoperative recovery. METHODS: This protocol will search multiple databases including PubMed/MEDLINE, Embase, Cochrane Library, CNKI, Scopus, and Web of Science to identify randomized controlled trials related to LIPUS for postoperative rehabilitation of rotator cuff tears. The search will encompass literature published from the inception of the databases up to April 2024. Methodological quality assessment and data extraction will be conducted using the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. Meta-analysis will be performed on appropriate studies using either random-effects or fixed-effects models, and subgroup analyses will be conducted to explore potential heterogeneity. Studies meeting the inclusion criteria will be included in the analysis. All analyses will be performed using Stata version 16.0. RESULTS: The incidence of rotator cuff tear rates will be assessed by imaging techniques such as MRI or ultrasound. Pain intensity will be scored using standardized pain assessment scales, such as the Visual Analog Scale (VAS). Improved range of motion (ROM) in shoulder flexion, abduction, and rotation. Functional outcomes will be evaluated using effective measures such as Constant-Murley scores (CMS) and shoulder joint scores by American Shoulder and Elbow Surgeons (ASES). Adverse events associated with LIPUS therapy, including skin irritation, increased pain, or any other complications. Subgroup analysis will also be carried out if possible. DISCUSSION AND CONCLUSION: Following the meta-analysis, we will assess the overall effect of LIPUS on postoperative rehabilitation of rotator cuff tears, and further explore its impact on aspects such as pain relief, functional improvement, and postoperative complications. It is anticipated that this study will provide comprehensive evidence regarding the role of LIPUS in postoperative rehabilitation of rotator cuff tears, guiding clinical practice and future research. The resultant manuscript will be submitted for publication in a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER: CRD42024530798.