{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:40:58Z","timestamp":1772728858090,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T00:00:00Z","timestamp":1616889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107-2314-B-002-045-MY3, MOST 107-2314-B-002-232-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-002-045-MY3, MOST 107-2314-B-002-232-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["NTUH 108-M4366, 108-M4277, 109-M4670"],"award-info":[{"award-number":["NTUH 108-M4366, 108-M4277, 109-M4670"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression\u2013edema\u2013ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat\u2019s sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineural cellular infiltration, deposition of irregular collagen fibers, and a possible early demyelination process, thus indicating the existence of adhesions. The novel method provides a surgery-free and cost-effective way to establish a small-animal model of EN that has mixed compression and adhesion features, thus facilitating the additional elucidation of the pathophysiology of EN and the search for promising treatments.<\/jats:p>","DOI":"10.3390\/ijms22073494","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T22:09:01Z","timestamp":1616969341000},"page":"3494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pathogenic Hydrogel? A Novel-Entrapment Neuropathy Model Induced by Ultrasound-Guided Perineural Injections"],"prefix":"10.3390","volume":"22","author":[{"given":"Ming-Yen","family":"Hsiao","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei 10048, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei 10048, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Wen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei 10048, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-5164","authenticated-orcid":false,"given":"Wen-Shiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei 10048, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei 10048, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei 10048, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei 10048, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9958-2204","authenticated-orcid":false,"given":"Po-Ling","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei 10048, Taiwan"},{"name":"Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3979-3541","authenticated-orcid":false,"given":"Chueh-Hung","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei 10048, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei 10048, Taiwan"},{"name":"Department of Physical Medicine &amp; Rehabilitation, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 302058, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/S1474-4422(16)30231-9","article-title":"Carpal tunnel syndrome: Clinical features, diagnosis, and management","volume":"15","author":"Padua","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_2","first-page":"4","article-title":"Pathophysiology of carpal tunnel syndrome","volume":"20","author":"Aboonq","year":"2015","journal-title":"Neurosciences"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1097\/01.prs.0000239593.55293.c7","article-title":"Changes in the Functional Structure of the Tenosynovium in Idiopathic Carpal Tunnel Syndrome: A Scanning Electron Microscope Study","volume":"118","author":"Ettema","year":"2006","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jelekin.2017.10.007","article-title":"The biomechanics of subsynovial connective tissue in health and its role in carpal tunnel syndrome","volume":"38","author":"Amadio","year":"2018","journal-title":"J. Electromyogr. Kinesiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.apmr.2008.07.028","article-title":"The Effects of Hypertonic Dextrose Injection on Connective Tissue and Nerve Conduction Through the Rabbit Carpal Tunnel","volume":"90","author":"Yoshii","year":"2009","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11552-013-9599-1","article-title":"Effects of Multiple Injections of Hypertonic Dextrose in the Rabbit Carpal Tunnel: A Potential Model of Carpal Tunnel Syndrome Development","volume":"9","author":"Yoshii","year":"2013","journal-title":"Hand"},{"key":"ref_7","first-page":"824","article-title":"Morphological changes of collagen fibrils in the subsynovial connective tissue in carpal tunnel syndrome","volume":"88","author":"Oh","year":"2006","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s10194-016-0665-2","article-title":"Contributions of p38 and ERK to the antinociceptive effects of TGF-beta1 in chronic constriction injury-induced neuropathic rats","volume":"17","author":"Chen","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/00000637-198408000-00004","article-title":"Chronic Nerve Compression\u2014An Experimental Model in the Rat","volume":"13","author":"MacKinnon","year":"1984","journal-title":"Ann. Plast. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1097\/00000637-198711000-00008","article-title":"A Model of Chronic Nerve Compression in the Rat","volume":"19","author":"MacKinnon","year":"1987","journal-title":"Ann. Plast. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neulet.2009.09.014","article-title":"c-Jun, krox-20, and integrin beta4 expression following chronic nerve compression injury","volume":"465","author":"Phame","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1021\/acsami.7b17020","article-title":"Injectable and Thermosensitive Hydrogel and PDLLA Electrospun Nanofiber Membrane Composites for Guided Spinal Fusion","volume":"10","author":"Qu","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jelekin.2003.09.009","article-title":"Entrapment neuropathies: Pathophysiology and pathogenesis","volume":"14","author":"Rempel","year":"2004","journal-title":"J. Electromyogr. Kinesiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0749-0712(21)00307-3","article-title":"The pathophysiology of carpal tunnel syndrome","volume":"12","author":"Kerwin","year":"1996","journal-title":"Hand Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0022-510X(75)90248-8","article-title":"Sub-clinical entrapment neuropathy in man","volume":"24","author":"Neary","year":"1975","journal-title":"J. Neurol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1055\/s-0034-1394133","article-title":"Carpal Tunnel Syndrome Pathophysiology: Role of Subsynovial Connective Tissue","volume":"3","author":"Werthel","year":"2014","journal-title":"J. Wrist Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00776-009-1416-x","article-title":"Current concepts of carpal tunnel syndrome: Pathophysiology, treatment, and evaluation","volume":"15","author":"Uchiyama","year":"2010","journal-title":"J. Orthop. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/micr.20071","article-title":"Biochemistry of carpal tunnel syndrome","volume":"25","author":"Sud","year":"2005","journal-title":"Microsurgery"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Peng, K.-T., Hsieh, M.Y., Lin, C.T., Chen, C.F., Lee, M.S., Huang, Y.Y., and Chang, P.J. (2016). Treatment of critically sized femoral defects with recombinant BMP-2 delivered by a modified mPEG-PLGA biodegradable thermosensitive hydrogel. BMC Musculoskelet. Disord., 17.","DOI":"10.1186\/s12891-016-1131-7"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104875","DOI":"10.1016\/j.ultsonch.2019.104875","article-title":"One injection for one-week controlled release: In vitro and in vivo assessment of ultrasound-triggered drug release from injectable thermoresponsive biocompatible hydrogels","volume":"62","author":"Wu","year":"2020","journal-title":"Ultrason. Sonochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.3171\/FOC.2009.26.2.E7","article-title":"Understanding the mechanisms of entrapment neuropathies","volume":"26","author":"Pham","year":"2009","journal-title":"Neurosurg. Focus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.orthres.2004.12.010","article-title":"Shear stress alters the expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) in Schwann cells","volume":"23","author":"Gupta","year":"2005","journal-title":"J. Orthop. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/cpr.12151","article-title":"Cyclic mechanical stress modulates neurotrophic and myelinating gene expression of Schwann cells","volume":"48","author":"Zhang","year":"2014","journal-title":"Cell Prolif."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/mus.26358","article-title":"Nerve hydrodissection for carpal tunnel syndrome: A prospective, randomized, double-blind, controlled trial","volume":"59","author":"Wu","year":"2019","journal-title":"Muscle Nerve"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1177\/1558944717731855","article-title":"Ultrasound-Guided Hydroneurolysis of the Median Nerve for Recurrent Carpal Tunnel Syndrome","volume":"14","author":"Fried","year":"2019","journal-title":"Hand"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.mayocp.2017.05.025","article-title":"Six-month Efficacy of Perineural Dextrose for Carpal Tunnel Syndrome: A Prospective, Randomized, Double-Blind, Controlled Trial","volume":"92","author":"Wu","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"625830","DOI":"10.3389\/fphar.2020.625830","article-title":"Volume Matters in Ultrasound-Guided Perineural Dextrose Injection for Carpal Tunnel Syndrome: A Randomized, Double-Blinded, Three-Arm Trial","volume":"11","author":"Lin","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.3233\/BME-141003","article-title":"Controlled release bevacizumab in thermoresponsive hydrogel found to inhibit angiogenesis","volume":"24","author":"Hu","year":"2014","journal-title":"Bio-Med. Mater. 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