Search Results (45)

Background: Previously, we found that the pathological changes in the corpus spongiosum (CS) in hypospadias were mainly localized within smooth muscle tissue, presenting as a transformation from the contraction phenotype to synthesis. The role of low-intensity pulsed ultrasound (LIPUS) in regulating smooth muscle cells (SMCs) and angiogenesis has been confirmed. Objectives: To demonstrate the feasibility of regulating the phenotypic transformation of corpus spongiosum smooth muscle cells (CSSMCs) in hypospadias using LIPUS and to explore the potential mechanisms. Materials and Methods: The CSSMCs were extracted from CS in patients with proximal hypospadias. In vitro experiments were conducted to explore the appropriate LIPUS irradiation intensity and duration which could promote the phenotypic transformation of CSSMCs. A total of 71 patients with severe hypospadias were randomly divided into a control group and a LIPUS group to verify the in vivo transition effect of LIPUS. Consequently, the potential mechanisms by which LIPUS regulates the phenotypic transformation of CSSMCs were explored in vitro. Results: In vitro experiments showed that LIPUS with an intensity of 100 mW/cm² and a duration of 10 min could significantly increase the expression of contraction markers in CSSMCs and decrease the expression of synthesis markers. Moreover, LIPUS stimulation could alter the phenotype of CSSMCs in patients with proximal hypospadias. RNA sequencing results revealed that peroxisome proliferator-activated receptor gamma (PPAR-γ) significantly increased after LIPUS stimulation. Overexpression of PPAR-γ significantly increased the expression of contraction markers in CSSMCs, and the knockdown of PPAR-γ blocked this effect. Conclusions: LIPUS can regulate the transition of CSSMCs from a synthetic to a contractile phenotype in hypospadias. The PPAR-γ-mediated signaling pathway is a possible mechanism involved in this process. Full article

Background: Gallbladder hypomotility is a key pathogenic factor in cholelithiasis. Non-invasive interventions to enhance gallbladder contractility remain limited. Ultrasound therapy has shown promise in various muscular disorders, but its effects on gallbladder function are unexplored. Methods: This study employed low-intensity pulsed ultrasound (LIPUS) at a 3 MHz frequency and 0.8 W/cm² intensity with a 20% duty cycle to irradiate the gallbladder region of fasting guinea pigs. Gallbladder contractile function was evaluated through multiple complementary approaches: in vivo assessment via two-dimensional/three-dimensional ultrasound imaging to monitor volumetric changes; quantitative functional evaluation using nuclear medicine scintigraphy (^99mTc-HIDA); and ex vivo experiments including isolated gallbladder muscle strip tension measurements, histopathological analysis, α-smooth muscle actin (α-SMA) immunohistochemistry, and intracellular calcium fluorescence imaging. Results: Ultrasound significantly enhanced gallbladder emptying, evidenced by the volume reduction and increased ejection fraction. Scintigraphy confirmed accelerated bile transport in treated animals. Ex vivo analyses demonstrated augmented contractile force, amplitude, and frequency in ultrasound-treated smooth muscle. Histological examination revealed smooth muscle hypertrophy, α-SMA upregulation, and elevated intracellular calcium levels. Extended ultrasound exposure produced sustained functional improvements without tissue damage. Conclusions: Ultrasound effectively enhances gallbladder contractile function through mechanisms involving smooth muscle structural modification and calcium signaling modulation. These findings establish the experimental foundation for ultrasound as a promising non-invasive therapeutic approach to improve gallbladder motility and potentially prevent gallstone formation. Full article

Bone regeneration demands biomaterials capable of supporting tissue integration and mimicking the native piezodynamic properties of bone. In this study, hydroxyapatite–barium titanate (HA-BT) composite coatings with varying BT content (10, 30, and 50 wt%) were developed to enhance the piezoelectric response and corrosion resistance of Ti6Al4V implants. The coatings were synthesized via high-energy ball milling and atmospheric plasma spraying (APS). XRD analysis with Rietveld refinement confirmed the presence of HA along with secondary phases (TTCP, β-TCP, CaO). Electrochemical tests revealed lower corrosion current densities for the coatings containing ≤30% BT, indicating improved stability in physiological environments. Cytotoxicity assays (MTT) demonstrated biocompatibility across all formulations. Piezoresponse force microscopy (DART-SS-PFM) confirmed enhanced d₃₃-eff values for the 50% BT coating (>15 pm/V); however, biological assays under low-intensity pulsed ultrasound (LIPUS) stimulation showed increased osteocalcin expression for ≤30% BT, while 50% BT induced cellular stress. Overall, HA-BT coatings with up to 30% BT exhibited optimal electrochemical stability, favorable piezoelectric performance, and enhanced biological response, underscoring their potential for orthopedic implant applications and regenerative tissue engineering. Full article

(1) Background: Ischemic stroke is a major global public-health concern with complex pathogenesis. Current treatment strategies face challenges. Low-intensity pulsed ultrasound stimulation (LIPUS), a non-invasive neuromodulation technology, shows promise in treating ischemic stroke, yet its underlying mechanisms lack in-depth investigation, especially in quantitative efficacy evaluation. (2) Methods: This study aimed to develop a neuromuscular functional coupling-based dynamic time warping (DTW) model to evaluate LIPUS’s neuroprotective effects in a mouse model of ischemic stroke. A bilateral carotid artery occlusion (BCAO) model in mice was established, and LIPUS treatment was given. Time- and frequency-domain analyses of local field potentials (LFPs) and electromyography (EMG) were conducted, and outcomes were quantified using a percentage-based scoring system. (3) Results: The BCAO+LIPUS group scored significantly higher than the BCAO group. (4) Conclusions: This study demonstrated that LIPUS is neuroprotective in BCAO mice and that the DTW-100 assessment evaluation model can quantify the neuroprotective effects of LIPUS. Full article

Conservative treatment is primarily performed for the treatment of patients with lumbar disc herniation (LDH), but if it does not respond, surgical treatment can be performed. Surgical intervention has a positive effect on the rapid improvement of LDH symptoms. However, the effectiveness of surgical versus conservative treatment for LDH is controversial, especially regarding long-term effects. Recently, a treatment using platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), low-intensity pulsed ultrasound (LIPUS), etc., has been actively conducted as a treatment to avoid side effects of surgery and promote tissue regeneration. In this paper, the literature evaluating the effectiveness of non-surgical treatment options is reviewed with an emphasis on the effectiveness of clinical application. Several clinical studies have shown that PRP, biomaterials, BMAC, and LIPUS treatment promote tissue regeneration and alleviate symptoms. Although PRP-applied studies have suggested disc height changes, cell therapy and LIPUS treatment have many shortcomings in clinical aspects of tissue regeneration. Therefore, it is necessary to establish a unified, safe protocol and standardize the method of presenting results to confirm the clinical effect of the treatment for impaired intervertebral regeneration in patients with intervertebral disc degeneration (IDD), including LDH. Full article

Background: Cholesterol gallstone disease (CGS) is often accompanied by gallbladder contraction dysfunction and chronic inflammation, but effective therapeutic options remain limited. This study investigates whether a low-intensity pulsed ultrasound (LIPUS) treatment can improve gallbladder motility and alleviate chronic inflammation while exploring the underlying mechanisms. Methods: Gallbladder motility was assessed through in vitro and in vivo contraction tests, while bile condition was evaluated by observing bile crystal clearance. Tissue analysis and Western blotting were performed to examine the expression of the cholecystokinin A receptor (CCKAR) and α-smooth muscle actin (α-SMA) as markers of gallbladder smooth muscle health and the inflammatory microenvironment. Blood cholesterol levels were measured via biochemical assays. Results: LIPUS treatment obviously enhanced gallbladder contractility in response to CCK-8 stimulation and accelerated bile crystal clearance. It also reduced inflammatory cell infiltration and tissue edema, and promoted new capillary formation in the gallbladder, mitigating the progression of CGS. Furthermore, LIPUS restored CCKAR expression and improved the thickness of the gallbladder smooth muscle layer, providing a structural basis for increased smooth muscle contractility. Conclusion: LIPUS improves gallbladder motility and reduces chronic inflammation in CGS by enhancing CCKAR expression and smooth muscle integrity. These findings highlight the potential of LIPUS as a non-invasive therapeutic approach for managing CGS. Full article

Background and Objectives: Cartilage repair remains a critical challenge in orthopaedic medicine due to the tissue’s limited self-healing ability, contributing to degenerative joint conditions such as osteoarthritis (OA). In response, regenerative medicine has developed advanced therapeutic strategies, including cell-based therapies, gene editing, and bioengineered scaffolds, to promote cartilage regeneration and restore joint function. This narrative review aims to explore the latest developments in cartilage repair techniques, focusing on mesenchymal stem cell (MSC) therapy, gene-based interventions, and biomaterial innovations. It also discusses the impact of patient-specific factors, such as age, defect size, and cost efficiency, on treatment selection and outcomes. Materials and Methods: This review synthesises findings from recent clinical and preclinical studies published within the last five years, retrieved from the PubMed, Scopus, and Web of Science databases. The search targeted key terms such as “cartilage repair”, “stem cell therapy”, “gene editing”, “biomaterials”, and “tissue engineering”. Results: Advances in MSC-based therapies, including autologous chondrocyte implantation (ACI) and platelet-rich plasma (PRP), have demonstrated promising regenerative potential. Gene-editing tools like CRISPR/Cas9 have facilitated targeted cellular modifications, while novel biomaterials such as hydrogels, biodegradable scaffolds, and 3D-printed constructs have improved mechanical support and tissue integration. Additionally, biophysical stimuli like low-intensity pulsed ultrasound (LIPUS) and electromagnetic fields (EMFs) have enhanced chondrogenic differentiation and matrix production. Treatment decisions are influenced by patient age, cartilage defect size, and financial considerations, highlighting the need for personalised and multimodal approaches. Conclusions: Combining regenerative techniques, including cell-based therapies, gene modifications, and advanced scaffolding, offers a promising pathway towards durable cartilage repair and joint preservation. Future research should focus on refining integrated therapeutic protocols, conducting long-term clinical evaluations, and embracing personalised treatment models driven by artificial intelligence and predictive algorithms. Full article

Peripheral nerve regeneration remains a major challenge in neuroscience, despite advancements in understanding its mechanisms. Current treatments, including nerve transplantation and drug therapies, face limitations such as invasiveness and incomplete recovery of nerve function. Physical therapies, like pulsed electromagnetic fields (PEMF) and low-intensity ultrasound (LIPUS), are gaining attention for their potential to enhance regeneration. This study analyzes the effects of PEMF and LIPUS on gene expression in human primary Schwann cells, which are crucial for nerve myelination and repair. Key genes involved in neurotrophin signaling (NGF, BDNF), inflammation (IL-1β, IL-6, IL-10, TNF-α, TGF-β), and regeneration (CRYAB, CSPG, Ki67) were assessed. The results of this study reveal that combined PEMF and LIPUS therapies promote Schwann cell proliferation, reduce inflammation, and improve the regenerative environment, offering potential for optimizing these therapies for clinical use in regenerative medicine. Full article

Porous Ti-6Al-4V scaffold materials can be used to heal massive bone defects because they can provide space for vascularisation and bone formation. During new bone tissue development, rapid vascular ingrowth into scaffold materials is very important. Osteoblast-derived exosomes are capable of facilitating angiogenesis–osteogenesis coupling. Low-intensity pulsed ultrasound (LIPUS) is a physical therapy modality widely utilised in the field of bone regeneration and has been proven to enhance the production and functionality of exosomes on two-dimensional surfaces. The impact of LIPUS on exosomes derived from osteoblasts cultured in three dimensions remains to be elucidated. In this study, exosomes produced by osteoblasts on porous Ti-6Al-4V scaffold materials under LIPUS and non-ultrasound stimulated conditions were co-cultured with endothelial cells. The findings indicated that the exosomes were consistently and stably taken up by the endothelial cells. Compared to the non-ultrasound group, the LIPUS group facilitated endothelial cell proliferation and angiogenesis. After 24 h of co-culture, the migration ability of endothelial cells in the LIPUS group was 17.30% higher relative to the non-ultrasound group. LIPUS may represent a potentially viable strategy to promote the efficacy of osteoblast-derived exosomes to enhance the angiogenesis of porous Ti-6Al-4V scaffold materials. Full article

Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that utilizes low-intensity pulsed waves. Its effect on bones that heal by intramembranous ossification has not been sufficiently investigated. In this study, we examined LIPUS and the autologous bone, to determine their effect on the healing of the critical-size bone defect (CSBD) of the rat calvaria. The bone samples underwent histological, histomorphometric and immunohistochemical analyses. Both LIPUS and autologous bone promoted osteogenesis, leading to almost complete closure of the bone defect. On day 30, the bone volume was the highest in the autologous bone group (20.35%), followed by the LIPUS group (19.12%), and the lowest value was in the control group (5.11%). The autologous bone group exhibited the highest intensities of COX-2 (167.7 ± 1.1) and Osx (177.1 ± 0.9) expression on day 30. In the LIPUS group, the highest intensity of COX-2 expression was found on day 7 (169.7 ±1.6) and day 15 (92.7 ± 2.2), while the highest Osx expression was on day 7 (131.9 ± 0.9). In conclusion, this study suggests that LIPUS could represent a viable alternative to autologous bone grafts in repairing bone defects that are ossified by intramembranous ossification. Full article

Low-intensity pulsed ultrasound (LIPUS) is a non-invasive medical therapy that has attracted recent research interest due to its therapeutic effects. However, most LIPUS driver systems currently available are large and expensive. We have proposed a LIPUS interface application-specific integrated circuit (ASIC) for use in wearable medical devices to address some of the challenges related to the size and cost of the current technologies. The proposed ASIC is a highly integrated system, incorporating a DCDC module based on a charge pump architecture, a high voltage level shifter, a half-bridge driver, a voltage-controlled oscillator, and a corresponding digital circuit module. Consequently, the functional realization of this ASIC as a LIPUS driver system requires only a few passive components. Experimental tests indicated that the chip is capable of an output of 184.2 mW or 107.2 mW with a power supply of 5 V or 3.7 V, respectively, and its power conversion efficiency is approximately 30%. This power output capacity allows the LIPUS driver system to deliver a spatial average temporal average (SATA) of 29.5 mW/cm² or 51.6 mW/cm² with a power supply of 3.7 V or 5 V, respectively. The total die area, including pads, is 4 mm². The ASIC does not require inductors, improving its magnetic resonance imaging (MRI) compatibility. In summary, the proposed LIPUS interface chip presents a promising solution for the development of MRI-compatible and cost-effective wearable medical therapy devices. Full article

In this work, electrospun polyvinylidene-trifluoroethylene (PVDF-TrFE) was utilized for its biocompatibility, mechanics, and piezoelectric properties to promote Schwann cell (SC) elongation and sensory neuron (SN) extension. PVDF-TrFE electrospun scaffolds were characterized over a variety of electrospinning parameters (1, 2, and 3 h aligned and unaligned electrospun fibers) to determine ideal thickness, porosity, and tensile strength for use as an engineered skin tissue. PVDF-TrFE was electrically activated through mechanical deformation using low-intensity pulsed ultrasound (LIPUS) waves as a non-invasive means to trigger piezoelectric properties of the scaffold and deliver electric potential to cells. Using this therapeutic modality, neurite integration in tissue-engineered skin substitutes (TESSs) was quantified including neurite alignment, elongation, and vertical perforation into PVDF-TrFE scaffolds. Results show LIPUS stimulation promoted cell alignment on aligned scaffolds. Further, stimulation significantly increased SC elongation and SN extension separately and in coculture on aligned scaffolds but significantly decreased elongation and extension on unaligned scaffolds. This was also seen in cell perforation depth analysis into scaffolds which indicated LIPUS enhanced perforation of SCs, SNs, and cocultures on scaffolds. Taken together, this work demonstrates the immense potential for non-invasive electric stimulation of an in vitro tissue-engineered-skin model. Full article

Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications. Full article

This study aims to present an ultrasound-mediated nanobubble (NB)-based gene delivery system that could potentially be applied in the future to treat bone disorders such as osteoporosis. NBs are sensitive to ultrasound (US) and serve as a controlled-released carrier to deliver a mixture of Cathepsin K (CTSK) siRNA and cerium oxide nanoparticles (CeNPs). This platform aimed to reduce bone resorption via downregulating CTSK expression in osteoclasts and enhance bone formation via the antioxidant and osteogenic properties of CeNPs. CeNPs were synthesized and characterized using transmission electron microscopy and X-ray photoelectron spectroscopy. The mixture of CTSK siRNA and CeNPs was adsorbed to the surface of NBs using a sonication method. The release profiles of CTSK siRNA and CeNPs labeled with a fluorescent tag molecule were measured after low-intensity pulsed ultrasound (LIPUS) stimulation using fluorescent spectroscopy. The maximum release of CTSK siRNA and the CeNPs for 1 mg/mL of NB-(CTSK siRNA + CeNPs) was obtained at 2.5 nM and 1 µg/mL, respectively, 3 days after LIPUS stimulation. Then, Alizarin Red Staining (ARS) was applied to human bone marrow-derived mesenchymal stem cells (hMSC) and tartrate-resistant acid phosphatase (TRAP) staining was applied to human osteoclast precursors (OCP) to evaluate osteogenic promotion and osteoclastogenic inhibition effects. A higher mineralization and a lower number of osteoclasts were quantified for NB-(CTSK siRNA + CeNPs) versus control +RANKL with ARS (p < 0.001) and TRAP-positive staining (p < 0.01). This study provides a method for the delivery of gene silencing siRNA and CeNPs using a US-sensitive NB system that could potentially be used in vivo and in the treatment of bone fractures and disorders such as osteoporosis. Full article

This study evaluated and compared the functional recovery and histopathological outcomes of treatment involving low-intensity pulsed ultrasound (LIPUS) and methylcobalamin (B12) on brachial plexus injury (BPI) in an experimental rat model. Three days after BPI, the rats were assigned to receive either LIPUS or methylcobalamin alone or in combination consecutively for 12 days. Serial changes in sensory and motor behavioral responses, as well as morphological and immunohistochemical changes for substance P (SP), ionized calcium-binding adapter molecule 1 (iba1), brain-derived neurotrophic factor (BDNF), and S100 were examined 28 days after BPI as the outcome measurements. Early intervention of LIPUS and methylcobalamin, whether alone or in combination, augmented the sensory and motor behavioral recovery as well as modulated SP and iba1 expression in spinal dorsal horns, BDNF, and S100 in the injured nerve. Moreover, the combined therapy with its synergistic effect gave the most beneficial effect in accelerating functional recovery. In view of the effective initiation of early recovery of sensory and motor functions, treatment with LIPUS and methylcobalamin in combination has a potential role in the clinical management of early-phase BPI. Full article