{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:35:37Z","timestamp":1792233337226,"version":"4.4.0"},"reference-count":85,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-18-1-0593"],"award-info":[{"award-number":["W81XWH-18-1-0593"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R01EB026094"],"award-info":[{"award-number":["R01EB026094"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NIBIB","award":["W81XWH-18-1-0593"],"award-info":[{"award-number":["W81XWH-18-1-0593"]}]},{"name":"NIH\/NIBIB","award":["R01EB026094"],"award-info":[{"award-number":["R01EB026094"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Research on the capability of non-viral gene delivery systems to induce tissue regeneration is a continued effort as the current use of viral vectors can present with significant limitations. Despite initially showing lower gene transfection and gene expression efficiencies, non-viral delivery methods continue to be optimized to match that of their viral counterparts. Ultrasound-mediated gene transfer, referred to as sonoporation, occurs by the induction of transient membrane permeabilization and has been found to significantly increase the uptake and expression of DNA in cells across many organ systems. In addition, it offers a more favorable safety profile compared to other non-viral delivery methods. Studies have shown that microbubble-enhanced sonoporation can elicit significant tissue regeneration in both ectopic and disease models, including bone and vascular tissue regeneration. Despite this, no clinical trials on the use of sonoporation for tissue regeneration have been conducted, although current clinical trials using sonoporation for other indications suggest that the method is safe for use in the clinical setting. In this review, we describe the pre-clinical studies conducted thus far on the use of sonoporation for tissue regeneration. Further, the various techniques used to increase the effectiveness and duration of sonoporation-induced gene transfer, as well as the obstacles that may be currently hindering clinical translation, are explored.<\/jats:p>","DOI":"10.3390\/bioengineering9050190","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T13:40:57Z","timestamp":1651066857000},"page":"190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Applications of Ultrasound-Mediated Gene Delivery in Regenerative Medicine"],"prefix":"10.3390","volume":"9","author":[{"given":"Zoe","family":"Krut","sequence":"first","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-0028","authenticated-orcid":false,"given":"Dan","family":"Gazit","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-0889","authenticated-orcid":false,"given":"Zulma","family":"Gazit","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3857-5531","authenticated-orcid":false,"given":"Gadi","family":"Pelled","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/cts.12736","article-title":"The Progression of Regenerative Medicine and its Impact on Therapy Translation","volume":"13","author":"Jacques","year":"2020","journal-title":"Clin. Transl. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jessop, Z.M., Al-Sabah, A., Francis, W.R., and Whitaker, I.S. (2016). Transforming healthcare through regenerative medicine. BMC Med., 14.","DOI":"10.1186\/s12916-016-0669-4"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/jbm.b.33354","article-title":"Gene delivery in tissue engineering and regenerative medicine","volume":"103","author":"Fang","year":"2015","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/978-1-4614-2098-9_17","article-title":"New Tools in Regenerative Medicine: Gene Therapy","volume":"741","author":"Ruiz","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1582-4934.2007.00027.x","article-title":"Gene transfer strategies in tissue engineering","volume":"11","author":"Bleiziffer","year":"2007","journal-title":"J. Cell. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40824-019-0156-z","article-title":"Recent advances in the development of gene delivery systems","volume":"23","author":"Sung","year":"2019","journal-title":"Biomater. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrg2141","article-title":"Engineering targeted viral vectors for gene therapy","volume":"8","author":"Waehler","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/bjp.2008.349","article-title":"Viral vectors: From virology to transgene expression","volume":"157","author":"Bouard","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1517\/14712598.2015.995086","article-title":"Viral vector-mediated transgenic cell therapy in regenerative medicine: Safety of the process","volume":"15","author":"Liu","year":"2014","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s13770-019-00179-x","article-title":"Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine","volume":"16","author":"Venkatesan","year":"2019","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/gt.2013.66","article-title":"Suicide gene approach using a dual-expression lentiviral vector to enhance the safety of ex vivo gene therapy for bone repair","volume":"21","author":"Alaee","year":"2013","journal-title":"Gene Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/2277-9175.98152","article-title":"Viral and nonviral delivery systems for gene delivery","volume":"1","author":"Nayerossadat","year":"2012","journal-title":"Adv. Biomed. Res."},{"key":"ref_13","first-page":"3","article-title":"The Mechanism of Naked DNA Uptake and Expression","volume":"54","author":"Wolff","year":"2005","journal-title":"Adv. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1007\/s11095-008-9719-8","article-title":"A Fibrin Glue Composition as Carrier for Nucleic Acid Vectors","volume":"25","author":"Schillinger","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1007\/s00264-014-2499-3","article-title":"Evaluation of fibrin-based gene-activated matrices for BMP2\/7 plasmid codelivery in a rat nonunion model","volume":"38","author":"Kaipel","year":"2014","journal-title":"Int. Orthop."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1515\/BC.2003.082","article-title":"The Magnetofection Method: Using Magnetic Force to Enhance Gene Delivery","volume":"384","author":"Plank","year":"2003","journal-title":"Biol. Chem."},{"key":"ref_17","first-page":"GE01","article-title":"Non viral vectors in gene therapy\u2014An overview","volume":"9","author":"Ramamoorth","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1208\/s12248-021-00608-7","article-title":"Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects","volume":"23","author":"Zu","year":"2021","journal-title":"AAPS J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/sj.gt.3301913","article-title":"Microbubble ultrasound improves the efficiency of gene transduction in skeletal muscle in vivo with reduced tissue damage","volume":"10","author":"Lu","year":"2003","journal-title":"Gene Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1208\/s12248-016-9982-2","article-title":"Bone Regeneration Using Gene-Activated Matrices","volume":"19","author":"Atluri","year":"2017","journal-title":"AAPS J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"598466","DOI":"10.3389\/fbioe.2020.598466","article-title":"Non-viral Gene Delivery Methods for Bone and Joints","volume":"8","author":"Gantenbein","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/sj.gt.3303070","article-title":"Ultrasound-based nonviral gene delivery induces bone formation in vivo","volume":"15","author":"Sheyn","year":"2007","journal-title":"Gene Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.5662\/wjm.v3.i4.39","article-title":"Sonoporation: Gene transfer using ultrasound","volume":"3","author":"Tomizawa","year":"2013","journal-title":"World J. Methodol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10976","DOI":"10.1073\/pnas.1917125117","article-title":"Acoustofluidic sonoporation for gene delivery to human hematopoietic stem and progenitor cells","volume":"117","author":"Belling","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.addr.2014.01.009","article-title":"Nucleic acid delivery with microbubbles and ultrasound","volume":"72","author":"Rychak","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.1073\/pnas.84.23.8463","article-title":"Transfection of mammalian cells with plasmid DNA by scrape loading and sonication loading","volume":"84","author":"Fechheimer","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/S0140-6736(99)01244-1","article-title":"Induction of cell-membrane porosity by ultrasound","volume":"353","author":"Tachibana","year":"1999","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1097\/01.rli.0000199292.88189.0f","article-title":"Microbubble contrast agents: Targeted ultrasound imaging and ultrasound-assisted drug-delivery applications","volume":"41","author":"Klibanov","year":"2006","journal-title":"Investig. Radiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e005459","DOI":"10.1161\/CIRCIMAGING.116.005459","article-title":"Safety with Echocardiographic Contrast Agents","volume":"10","author":"Muskula","year":"2017","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"426710","DOI":"10.1155\/2014\/426710","article-title":"Effect of Nonviral Plasmid Delivered Basic Fibroblast Growth Factor and Low Intensity Pulsed Ultrasound on Mandibular Condylar Growth: A Preliminary Study","volume":"2014","author":"Kaur","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e250","DOI":"10.1002\/term.2406","article-title":"Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation","volume":"12","author":"Nomikou","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/term.1730","article-title":"Ultrasound-mediated gene transfer (sonoporation) in fibrin-based matrices: Potential for use in tissue regeneration","volume":"10","author":"Nomikou","year":"2016","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.addr.2013.11.008","article-title":"Understanding ultrasound induced sonoporation: Definitions and underlying mechanisms","volume":"72","author":"Lentacker","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ultsonch.2015.12.001","article-title":"Effect of non-acoustic parameters on heterogeneous sonoporation mediated by single-pulse ultrasound and microbubbles","volume":"31","author":"Qin","year":"2016","journal-title":"Ultrason. Sonochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/hgtb.2013.113","article-title":"Sonoporation Increases Therapeutic Efficacy of Inducible and Constitutive BMP2\/7 In Vivo Gene Delivery","volume":"25","author":"Feichtinger","year":"2014","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.actbio.2011.09.010","article-title":"Studies on neutral, cationic and biotinylated cationic microbubbles in enhancing ultrasound-mediated gene delivery in vitro and in vivo","volume":"8","author":"Nomikou","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.canlet.2008.07.030","article-title":"Optimising ultrasound-mediated gene transfer (sonoporation) in vitro and prolonged expression of a transgene in vivo: Potential applications for gene therapy of cancer","volume":"273","author":"Li","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1097\/01.brs.0000219945.70675.dd","article-title":"Sustained Transgene Expression in Intervertebral Disc Cells In Vivo Mediated by Microbubble-Enhanced Ultrasound Gene Therapy","volume":"31","author":"Nishida","year":"2006","journal-title":"Spine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"eaal3128","DOI":"10.1126\/scitranslmed.aal3128","article-title":"In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs","volume":"9","author":"Bez","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1016\/j.ymthe.2018.04.020","article-title":"Ultrasound-Mediated Gene Delivery Enhances Tendon Allograft Integration in Mini-Pig Ligament Reconstruction","volume":"26","author":"Bez","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.canlet.2008.02.041","article-title":"Enhancing ultrasound-mediated cell membrane permeabilisation (sonoporation) using a high frequency pulse regime and implications for ultrasound-aided cancer chemotherapy","volume":"266","author":"Li","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.addr.2012.03.009","article-title":"Naturally and synthetic smart composite biomaterials for tissue regeneration","volume":"65","author":"Perez","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/jgm.1331","article-title":"Osteoinduction by microbubble-enhanced transcutaneous sonoporation of human bone morphogenetic protein-2","volume":"11","author":"Osawa","year":"2009","journal-title":"J. Gene Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.jcmg.2009.04.008","article-title":"Ultrasound-Targeted Gene Delivery Induces Angiogenesis After a Myocardial Infarction in Mice","volume":"2","author":"Fujii","year":"2009","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2015.11.020","article-title":"Increased local delivery of antagomir therapeutics to the rodent myocardium using ultrasound and microbubbles","volume":"222","author":"Kwekkeboom","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1093\/eurheartj\/ehq475","article-title":"Repeated and targeted transfer of angiogenic plasmids into the infarcted rat heart via ultrasound targeted microbubble destruction enhances cardiac repair","volume":"32","author":"Fujii","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1016\/j.biomaterials.2012.11.041","article-title":"The use of cationic microbubbles to improve ultrasound-targeted gene delivery to the ischemic myocardium","volume":"34","author":"Sun","year":"2013","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/sj.gt.3301678","article-title":"Development of safe and efficient novel nonviral gene transfer using ultrasound: Enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle","volume":"9","author":"Taniyama","year":"2002","journal-title":"Gene Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1161\/CIRCRESAHA.107.148676","article-title":"Therapeutic Arteriogenesis by Ultrasound-Mediated VEGF165 Plasmid Gene Delivery to Chronically Ischemic Skeletal Muscle","volume":"101","author":"Kuliszewski","year":"2007","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.jacc.2009.07.023","article-title":"Comparison of Gene Delivery Techniques for Therapeutic Angiogenesis: Ultrasound-Mediated Destruction of Carrier Microbubbles Versus Direct Intramuscular Injection","volume":"54","author":"Kobulnik","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.jacc.2011.12.025","article-title":"Sustained Improvement in Perfusion and Flow Reserve After Temporally Separated Delivery of Vascular Endothelial Growth Factor and Angiopoietin-1 Plasmid Deoxyribonucleic Acid","volume":"59","author":"Smith","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1161\/ATVBAHA.115.306506","article-title":"Therapeutic Angiogenesis by Ultrasound-Mediated MicroRNA-126-3p Delivery","volume":"35","author":"Cao","year":"2015","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/gt.2010.85","article-title":"Regeneration of pancreatic islets in vivo by ultrasound-targeted gene therapy","volume":"17","author":"Chen","year":"2010","journal-title":"Gene Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.4161\/cc.19928","article-title":"Ectopic transgenic expression of NKX2.2 induces differentiation of adult pancreatic progenitors and mediates islet regeneration","volume":"11","author":"Chen","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"695","DOI":"10.4161\/cc.11.4.19120","article-title":"Transient overexpression of cyclin D2\/CDK4\/GLP1 genes induces proliferation and differentiation of adult pancreatic progenitors and mediates islet regeneration","volume":"11","author":"Chen","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1007\/s00125-015-3521-z","article-title":"In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in rats","volume":"58","author":"Chen","year":"2015","journal-title":"Diabetologia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"216","DOI":"10.4248\/BR201303002","article-title":"Bone Regeneration Based on Tissue Engineering Conceptions\u2014A 21st Century Perspective","volume":"1","author":"Henkel","year":"2013","journal-title":"Bone Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/mt.2010.190","article-title":"Targeted Gene-and-host Progenitor Cell Therapy for Nonunion Bone Fracture Repair","volume":"19","author":"Pelled","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nbt0998-867","article-title":"Gene transfer into muscle by electroporation in vivo","volume":"16","author":"Aihara","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/sj.gt.3301692","article-title":"Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth\/differentiation factor 11 (Gdf11)","volume":"9","author":"Nakashima","year":"2002","journal-title":"Gene Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/cgt.2011.73","article-title":"Sonoporation-mediated anti-angiogenic gene transfer into muscle effectively regresses distant orthotopic tumors","volume":"19","author":"Liao","year":"2011","journal-title":"Cancer Gene Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/sj.gt.3300718","article-title":"Inflammatory responses following direct injection of plasmid DNA into skeletal muscle","volume":"5","author":"McMahon","year":"1998","journal-title":"Gene Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/sj.gt.3302956","article-title":"Delayed administration of adenoviral BMP-2 vector improves the formation of bone in osseous defects","volume":"14","author":"Betz","year":"2007","journal-title":"Gene Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ultras.2009.09.035","article-title":"Ultrasound-assisted microbubbles gene transfer in tendons for gene therapy","volume":"50","author":"Delalande","year":"2010","journal-title":"Ultrasonics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jconrel.2015.12.001","article-title":"Multiparameter evaluation of in vivo gene delivery using ultrasound-guided, microbubble-enhanced sonoporation","volume":"223","author":"Shapiro","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1093\/cvr\/cvn292","article-title":"Post-infarct remodelling: Contribution of wound healing and inflammation","volume":"81","author":"Frantz","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/gt.2012.89","article-title":"Stimulation of adult resident cardiac progenitor cells by durable myocardial expression of thymosin beta 4 with ultrasound-targeted microbubble delivery","volume":"20","author":"Chen","year":"2012","journal-title":"Gene Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7088","DOI":"10.7150\/thno.34895","article-title":"Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function","volume":"9","author":"Kopechek","year":"2019","journal-title":"Theranostics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1111\/echo.12876","article-title":"Ultrasound-Targeted Microbubble Destruction Enhances Gene Expression of microRNA-21 in Swine Heart via Intracoronary Delivery","volume":"32","author":"Liu","year":"2015","journal-title":"Echocardiography"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.ultrasmedbio.2022.01.004","article-title":"Pre-transplantation of Bone Marrow Mesenchymal Stem Cells Amplifies the Therapeutic Effect of Ultrasound-Targeted Microbubble Destruction\u2013Mediated Localized Combined Gene Therapy in Post-Myocardial Infarction Heart Failure Rats","volume":"48","author":"Wang","year":"2022","journal-title":"Ultrasound Med. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/iub.1658","article-title":"Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design","volume":"69","author":"Bastarrachea","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1089\/104303403764539369","article-title":"Induction of Reparative Dentin Formation by Ultrasound-Mediated Gene Delivery of Growth\/Differentiation Factor 11","volume":"14","author":"Nakashima","year":"2003","journal-title":"Hum. Gene Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1177\/00220345940730090601","article-title":"Induction of Dentin Formation on Canine Amputated Pulp by Recombinant Human Bone Morphogenetic Proteins (BMP)-2 and -4","volume":"73","author":"Nakashima","year":"1994","journal-title":"J. Dent. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/jre.12119","article-title":"Gene delivery to periodontal tissue using Bubble liposomes and ultrasound","volume":"49","author":"Sugano","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"668754","DOI":"10.3389\/fphar.2021.668754","article-title":"Minoxidil-Coated Lysozyme-Shelled Microbubbes Combined with Ultrasound for the Enhancement of Hair Follicle Growth: Efficacy In Vitro and In Vivo","volume":"12","author":"Liao","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"119736","DOI":"10.1016\/j.biomaterials.2019.119736","article-title":"Ultrasound-activated particles as CRISPR\/Cas9 delivery system for androgenic alopecia therapy","volume":"232","author":"Ryu","year":"2020","journal-title":"Biomaterials"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.clinimag.2012.02.017","article-title":"Attenuation of hepatic fibrosis through ultrasound-microbubble-mediated HGF gene transfer in rats","volume":"37","author":"Jiang","year":"2013","journal-title":"Clin. Imaging"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1038\/gt.2013.41","article-title":"Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and cationic liposome-bearing microbubbles","volume":"20","author":"Yang","year":"2013","journal-title":"Gene Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"113847","DOI":"10.1016\/j.addr.2021.113847","article-title":"Ultrasound and microbubbles to beat barriers in tumors: Improving delivery of nanomedicine","volume":"177","author":"Snipstad","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1158\/1078-0432.CCR-18-3643","article-title":"Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma","volume":"25","author":"Idbaih","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1166\/jbn.2019.2776","article-title":"Ultrasound-Targeted Microbubble Destruction-Mediated Co-Delivery of Cxcl12 (Sdf-1alpha) and Bmp2 Genes for Myocardial Repair","volume":"15","author":"Yang","year":"2019","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_82","first-page":"547","article-title":"Low-Intensity Pulsed Ultrasound Stimulation for Bone Fractures Healing: A Review","volume":"41","author":"Be","year":"2021","journal-title":"J. Ultrasound Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Yuana, Y., Jiang, L., Lammertink, B.H.A., Vader, P., Deckers, R., Bos, C., Schiffelers, R.M., and Moonen, C.T. (2017). Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081610"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jconrel.2013.03.017","article-title":"Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound","volume":"169","author":"Rifai","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Filippi, M., Dasen, B., and Scherberich, A. (2021). Rapid Magneto-Sonoporation of Adipose-Derived Cells. Materials, 14.","DOI":"10.3390\/ma14174877"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/9\/5\/190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:02:02Z","timestamp":1760137322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/9\/5\/190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":85,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["bioengineering9050190"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering9050190","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]}}}