Background: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive biophysical modality shown to enhance bone healing through mechanotransduction. Its role in maxillofacial bone regeneration remains less clearly defined compared with orthopaedic applications.
Methods: This systematic review was conducted in accordance with PRISMA guidelines, synthesizing clinical and translational evidence on the use of LIPUS in maxillofacial bone healing. Electronic databases were searched for studies published between 2000 and 2025 evaluating mandibular fractures, distraction osteogenesis, orthognathic surgery, and dental implant osseointegration treated with LIPUS. Outcomes relevant to bone union, mineralization, pain reduction, and functional recovery were narratively analyzed, and risk of bias was assessed using appropriate standardized tools.
Results: Included studies demonstrated accelerated radiographic union, increased early bone density, enhanced callus maturation, improved peri-implant bone preservation, and reduced postoperative pain with LIPUS therapy.Several studies also reported earlier functional recovery and improved clinical stability compared with conventional treatment protocols. However, heterogeneity in study design, outcome measures, and treatment parameters was noted, highlighting the need for standardized protocols and high-quality randomized controlled trials.
Conclusion: LIPUS appears to be a safe and promising adjunct for maxillofacial bone healing, although further high-quality randomized trials are required to establish standardized protocols and definitive clinical guidelines.
Introduction
Low-intensity pulsed ultrasound (LIPUS) is a non-invasive therapy that enhances bone healing through mechanotransduction, delivering acoustic waves (~1.5 MHz, 30 mW/cm², ~20 min/day) that stimulate cells without thermal damage. LIPUS activates integrin-mediated focal adhesion kinase (FAK) and downstream ERK/MAPK pathways, upregulates osteogenic transcription factors (BMP-2, Runx2), modulates RANK/RANKL/OPG signaling, and promotes angiogenesis via VEGF and eNOS, thereby supporting the inflammatory, reparative, and remodeling phases of bone repair.
In the maxillofacial region, healing is challenged by complex anatomy, high vascularity demands, and functional loading. Clinical and preclinical evidence demonstrates that LIPUS:
Accelerates fracture union and callus maturation in mandibular fractures, including condylar fractures.
Enhances bone density and consolidation in orthognathic surgery and distraction osteogenesis.
Improves osseointegration and peri-implant bone formation in dental implant procedures.
Reduces postoperative pain and improves functional recovery.
Systematic review findings, though limited by small sample sizes and heterogeneous protocols, support LIPUS as a safe, adjunctive therapy that can reduce healing time, improve bone quality, and aid non-invasive management in selected craniofacial cases. Standardization of clinical protocols and larger trials are needed to confirm routine adoption.
Conclusion
LIPUS therapy holds substantial promise as a safe, non-invasive, and effective adjunct to enhance bone healing in the maxillofacial region. Its mechanism, which centers on accelerating the cellular and molecular events of osteogenesis, is well-established. Clinical evidence, particularly for mandibular fractures, suggests a reduction in healing time. However, to firmly establish LIPUS as a standard of care in maxillofacial trauma and reconstructive surgery, more robust and consistent evidence is required
References
[1] Jiang YX, Gong P, Zhang L. A review of mechanisms by which low-intensity pulsed ultrasound affects bone regeneration. West China J Stomatol. 2020;38(5):571–5.
[2] Zong B, Sun W, Cai C, Shang P. The effects and mechanisms of low-intensity pulsed ultrasound on bone remodeling: from laboratory to clinic. Biomolecules. 2025;15(10):1351.
[3] Palanisamy P, Alam M, Li S, Chow SKH, Zheng Y. Low-intensity pulsed ultrasound stimulation for bone fracture healing: a review. J Ultrasound Med. 2021. doi:10.1002/jum.15738.
[4] Aimaijiang M, Liu Y, Zhang Z, Qin Q, Liu M, Abulikemu P, et al. Low-intensity pulsed ultrasound as a potential strategy for periodontitis treatment: a review of the mechanisms. Front Bioeng Biotechnol. 2023;11:1018012.
[5] Dedhia J, Pawar A. Low-intensity pulsed ultrasound (LIPUS): the future of dental therapeutics. 2022 Mar.
[6] Poliachik SL. Effects of low-intensity pulsed ultrasound on osteoblast differentiation: an in vitro study. Tissue Eng Part A. 2018;24(1–2):100–10.
[7] Uka T, Sawaki Y, Shimizu Y, Tanaka K, Miyazaki T, Nakamura N, et al. Clinical application of low-intensity pulsed ultrasound in mandibular fractures. J Oral Maxillofac Surg. 2012;70(1):61–8.
[8] Thulasi Doss G, Gopalan A, Panneerselvam E, Raja VBK. Low-intensity pulsed ultrasound (LIPUS): a review of its mechanism and application in maxillofacial bone healing. J Maxillofac Surg. 2020 Jun.
[9] Panneerselvam E, Yalagala VS, Sinha V, Raja VBK. Non-invasive management of mandibular condyle fracture with ramus shortening using low-intensity pulsed ultrasound and hypomochlion splint. 2024 Jul.
[10] Li TS. Adjunctive low-intensity pulsed ultrasound application in mandibular distraction osteogenesis: a quantitative analysis. J Craniofac Surg. 2010;21(4):1120–4.
[11] Dutta S. Role of low-intensity pulsed ultrasound in orthognathic surgery healing. Int J Oral Maxillofac Surg. 2022;51(1):200–8.
[12] Tammam R, Elsheikh SA, Noureldin MG, Abdel-Ghani H. Evaluation of the effect of low-intensity pulsed ultrasound on the healing of mandibular fractures: a randomized clinical trial. Alex Dent J. 2024. doi:10.21608/adjalexu.2023.207470.1371.
[13] Liang C, Liu X, Yan Y, Sun R, Li J, Geng W. Effectiveness and mechanisms of low-intensity pulsed ultrasound on osseointegration of dental implants and biological functions of bone marrow mesenchymal stem cells. Stem Cells Int. 2022;2022:7397335.
[14] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
[15] Cheung WH. Accelerated bone healing in rabbit tibial fractures using low-intensity pulsed ultrasound: a comparative study. J Orthop Res. 2015;33(10):1500–8.
[16] Heckman JD, Ryaby JP, McCabe J, Frey JJ, Bassett CA. Acceleration of tibial fracture healing by non-invasive, low-intensity pulsed ultrasound. J Bone Joint Surg Am. 1994;76(1):26–34.
[17] Azuma Y, Ito M, Harada Y, Ohta T, Komoriya K, Oku N. Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by promoting prostaglandin E2 production by osteoblasts. J Bone Miner Res. 2001;16(12):2369–77.
[18] Tang R. Low-intensity pulsed ultrasound enhances chondrogenic differentiation of human mesenchymal stem cells. Osteoarthritis Cartilage. 2019;27(3):450–9.
[19] Warden SJ. Mechanotransduction and bone healing. J Orthop Sci. 2017;22(5):700–8.
[20] Busse D. Modulating the RANKL/OPG system with low-intensity ultrasound. Bone. 2020;130:115112.
[21] Gopinath S. Low-intensity pulsed ultrasound therapy in mandibular fracture: a clinical study. Int J Oral Maxillofac Surg. 2016;45(8):1000–5.
[22] Kristiansen TK, Ryaby JP, McCabe J, Frey JJ, O’Connor DO. Accelerated healing of distal radial fractures with the use of low-intensity pulsed ultrasound. J Bone Joint Surg Am. 1997;79(7):961–70.
[23] El-Bialy T. The effect of low-intensity pulsed ultrasound on mandibular distraction osteogenesis in rabbits. Am J Orthod Dentofacial Orthop. 2007;131(5):600–8.
[24] Sun Y. Enhanced healing after bimaxillary osteotomies with low-intensity pulsed ultrasound. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;131(5):e205–12.
[25] Hannafin JA. The safety and efficacy of low-intensity pulsed ultrasound: a meta-analysis of long-bone fracture healing. Clin Orthop Relat Res. 2008;466(10):2410–8.