{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T16:21:09Z","timestamp":1768321269132,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T00:00:00Z","timestamp":1534896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["14-14961S"],"award-info":[{"award-number":["14-14961S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["17-11140S"],"award-info":[{"award-number":["17-11140S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["LO1309"],"award-info":[{"award-number":["LO1309"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Operational Programme Research, Development and Education in the framework of the project &quot;Centre of Reconstructive Neuroscience &quot;,","award":["CZ.02.1.01\/0.0.\/0.0\/15_003\/0000419"],"award-info":[{"award-number":["CZ.02.1.01\/0.0.\/0.0\/15_003\/0000419"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methacrylate hydrogels have been extensively used as bridging scaffolds in experimental spinal cord injury (SCI) research. As synthetic materials, they can be modified, which leads to improved bridging of the lesion. Fibronectin, a glycoprotein of the extracellular matrix produced by reactive astrocytes after SCI, is known to promote cell adhesion. We implanted 3 methacrylate hydrogels: a scaffold based on hydroxypropylmethacrylamid (HPMA), 2-hydroxyethylmethacrylate (HEMA) and a HEMA hydrogel with an attached fibronectin (HEMA-Fn) in an experimental model of acute SCI in rats. The animals underwent functional evaluation once a week and the spinal cords were histologically assessed 3 months after hydrogel implantation. We found that both the HPMA and the HEMA-Fn hydrogel scaffolds lead to partial sensory improvement compared to control animals and animals treated with plain HEMA scaffold. The HPMA scaffold showed an increased connective tissue infiltration compared to plain HEMA hydrogels. There was a tendency towards connective tissue infiltration and higher blood vessel ingrowth in the HEMA-Fn scaffold. HPMA hydrogels showed a significantly increased axonal ingrowth compared to HEMA-Fn and plain HEMA; while there were some neurofilaments in the peripheral as well as the central region of the HEMA-Fn scaffold, no neurofilaments were found in plain HEMA hydrogels. In conclusion, HPMA hydrogel as well as the HEMA-Fn scaffold showed better bridging qualities compared to the plain HEMA hydrogel, which resulted in very limited partial sensory improvement.<\/jats:p>","DOI":"10.3390\/ijms19092481","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T03:00:46Z","timestamp":1534993246000},"page":"2481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Modified Methacrylate Hydrogels Improve Tissue Repair after Spinal Cord Injury"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-1980","authenticated-orcid":false,"given":"Ale\u0161","family":"Hej\u010dl","sequence":"first","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"},{"name":"Department of Neurosurgery, J. E. Purkinje University, Masaryk Hospital, Soci\u00e1ln\u00ed P\u00e9\u010de 12A, 401 13 \u00dast\u00ed nad Labem, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u0159\u00ed","family":"R\u016f\u017ei\u010dka","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6451-9707","authenticated-orcid":false,"given":"Krist\u00fdna","family":"Kekulov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Svobodov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-7120","authenticated-orcid":false,"given":"Vladim\u00edr","family":"Proks","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsk\u00e9ho n\u00e1m.2, 162 06 Praha, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Mackov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsk\u00e9ho n\u00e1m.2, 162 06 Praha, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate\u0159ina","family":"Jir\u00e1nkov\u00e1","sequence":"additional","affiliation":[{"name":"Second Faculty of Medicine, Charles University, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krist\u00fdna","family":"K\u00e1rov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"},{"name":"Department of Neuroscience, 2nd Faculty of Medicine, Charles University, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Machov\u00e1 Urdzikov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0160\u00e1rka","family":"Kubinov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u0159\u00ed","family":"Cihl\u00e1\u0159","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Faculty of Science, J. E. Purkyn\u011b University, \u010cesk\u00e9 Ml\u00e1de\u017ee 8, 400 96 \u00dast\u00ed nad Labem, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Hor\u00e1k","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsk\u00e9ho n\u00e1m.2, 162 06 Praha, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4644-9212","authenticated-orcid":false,"given":"Pavla","family":"Jendelov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 142 20 Prague, Czech Republic"},{"name":"Department of Neuroscience, 2nd Faculty of Medicine, Charles University, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,22]]},"reference":[{"key":"ref_1","unstructured":"Atala, R., Langer, R., Thomson, J., and Nerem, R. (2008). Principles of Regenerative Medicine, Academic Press."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1021\/bm900366e","article-title":"Hydrogels cross-linked by native chemical ligation","volume":"10","author":"Hu","year":"2009","journal-title":"Biomacromolecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1002\/adma.200802106","article-title":"Hydrogels in regenerative medicine","volume":"21","author":"Slaughter","year":"2009","journal-title":"Adv. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1016\/S0142-9612(03)00340-5","article-title":"Hydrogels for tissue engineering: Scaffold design variables and applications","volume":"24","author":"Drury","year":"2003","journal-title":"Biomaterials"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(01)00239-3","article-title":"Hydrogels for biomedical applications","volume":"54","author":"Hoffman","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1021\/ma901530r","article-title":"Polymer scaffolds for Biomaterials Applications","volume":"43","author":"Shoichet","year":"2010","journal-title":"Macromolecules"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"914","DOI":"10.5966\/sctm.2015-0381","article-title":"Concise Review: Bridging the Gap: Novel Neuroregenerative and Neuroprotective Strategies in Spinal Cord Injury","volume":"5","author":"Ahuja","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.nbd.2014.03.018","article-title":"Long-lasting significant functional improvement in chronic severe spinal cord injury following scar resection and polyethylene glycol implantation","volume":"67","author":"Estrada","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/dneu.20540","article-title":"Laminin and fibronectin modulate inner ear spiral ganglion neurite outgrowth in an in vitro alternate choice assay","volume":"67","author":"Evans","year":"2007","journal-title":"Dev. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1089\/neu.2008.0610","article-title":"Axon regeneration through scaffold into distal spinal cord after transection","volume":"26","author":"Chen","year":"2009","journal-title":"J. Neurotrauma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0142-9612(00)00278-7","article-title":"Oriented Schwann cell growth on micropatterned biodegradable polymer substrates","volume":"22","author":"Miller","year":"2001","journal-title":"Biomaterials"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1089\/neu.2014.3703","article-title":"Fibronectin Matrix Assembly after Spinal Cord Injury","volume":"32","author":"Zhu","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.biomaterials.2007.11.033","article-title":"Biodegradable poly-beta-hydroxybutyrate scaffold seeded with Schwann cells to promote spinal cord repair","volume":"29","author":"Novikova","year":"2008","journal-title":"Biomaterials"},{"key":"ref_14","first-page":"996","article-title":"Extracellular matrix. 2: Role of extracellular matrix molecules and their receptors in the nervous system","volume":"7","author":"Venstrom","year":"1993","journal-title":"Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1523\/JNEUROSCI.0143-08.2008","article-title":"Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury","volume":"28","author":"Sahni","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S121","DOI":"10.33549\/physiolres.931606","article-title":"Biocompatible hydrogels in spinal cord injury repair","volume":"57","author":"Hejcl","year":"2008","journal-title":"Physiol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1007\/s10856-006-0611-y","article-title":"Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 5: Hydrolytically degradable materials","volume":"17","author":"Pradny","year":"2006","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/jbm.a.33221","article-title":"Highly superporous cholesterol-modified poly(2-hydroxyethyl methacrylate) scaffolds for spinal cord injury repair","volume":"99","author":"Kubinova","year":"2011","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/jbm.a.36311","article-title":"Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with rgd as scaffold for spinal cord injury repair","volume":"106","author":"Zaviskova","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s10571-006-9007-2","article-title":"Bone marrow stem cells and polymer hydrogels\u2014Two strategies for spinal cord injury repair","volume":"26","author":"Sykova","year":"2006","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3171\/SPI-08\/01\/067","article-title":"Acute and delayed implantation of positively charged 2-hydroxyethyl methacrylate scaffolds in spinal cord injury in the rat","volume":"8","author":"Hejcl","year":"2008","journal-title":"J. Neurosurg. Spine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/term.1694","article-title":"SIKVAV-modified highly superporous PHEMA scaffolds with oriented pores for spinal cord injury repair","volume":"9","author":"Kubinova","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1089\/scd.2012.0616","article-title":"Adjusting the chemical and physical properties of hydrogels leads to improved stem cell survival and tissue ingrowth in spinal cord injury reconstruction: A comparative study of four methacrylate hydrogels","volume":"22","author":"Hejcl","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1007\/s10856-009-3714-4","article-title":"Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydrogels with positive and negative surface charges and polyelectrolyte complexes in spinal cord injury repair","volume":"20","author":"Hejcl","year":"2009","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1089\/scd.2009.0378","article-title":"HPMA-RGD hydrogels seeded with mesenchymal stem cells improve functional outcome in chronic spinal cord injury","volume":"19","author":"Hejcl","year":"2010","journal-title":"Stem Cells Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9295","DOI":"10.1021\/la801472x","article-title":"Novel pH-responsive nanoparticles","volume":"24","author":"Filippov","year":"2008","journal-title":"Langmuir"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10616-015-9895-4","article-title":"Scaffolds and cells for tissue regeneration: Different scaffold pore sizes-different cell effects","volume":"68","author":"Bruzauskaite","year":"2016","journal-title":"Cytotechnology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1016\/S0142-9612(03)00334-X","article-title":"Fiber templating of poly(2-hydroxyethyl methacrylate) for neural tissue engineering","volume":"24","author":"Flynn","year":"2003","journal-title":"Biomaterials"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/S0142-9612(00)00354-9","article-title":"Spinal cord repair with PHPMA hydrogel containing RGD peptides (NeuroGel)","volume":"22","author":"Woerly","year":"2001","journal-title":"Biomaterials"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-3-7091-0673-0_3","article-title":"Experimental reconstruction of the injured spinal cord","volume":"37","author":"Hejcl","year":"2011","journal-title":"Adv. Technol. Stand. Neurosurg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1006\/exnr.2001.7692","article-title":"The regrowth of axons within tissue defects in the CNS is promoted by implanted hydrogel matrices that contain BDNF and CNTF producing fibroblasts","volume":"170","author":"Loh","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1006\/exnr.1997.6407","article-title":"Hydrogels containing peptide or aminosugar sequences implanted into the rat brain: Influence on cellular migration and axonal growth","volume":"143","author":"Plant","year":"1997","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000339589","article-title":"Localized and sustained delivery of fibroblast growth factor-2 from a nanoparticle-hydrogel composite for treatment of spinal cord injury","volume":"197","author":"Kang","year":"2013","journal-title":"Cells Tissues Organs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jcp.1137","article-title":"Fibronectin, integrins, and growth control","volume":"189","author":"Danen","year":"2001","journal-title":"J. Cell Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1755-1536-4-21","article-title":"Plasma and cellular fibronectin: Distinct and independent functions during tissue repair","volume":"4","author":"To","year":"2011","journal-title":"Fibrog. Tissue Repair"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1016\/j.biomaterials.2010.02.018","article-title":"The use of injectable forms of fibrin and fibronectin to support axonal ingrowth after spinal cord injury","volume":"31","author":"King","year":"2010","journal-title":"Biomaterials"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/85471","article-title":"Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis","volume":"7","author":"Sakai","year":"2001","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.neuroscience.2010.03.040","article-title":"The neuroprotective effects of fibronectin mats and fibronectin peptides following spinal cord injury in the rat","volume":"168","author":"King","year":"2010","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10856-018-6100-2","article-title":"Dynamics of tissue ingrowth in SIKVAV-modified highly superporous PHEMA scaffolds with oriented pores after bridging a spinal cord transection","volume":"29","author":"Hejcl","year":"2018","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1055\/s-2006-946711","article-title":"Free vascularized lateral femoral cutaneous nerve graft with anterolateral thigh flap for reconstruction of facial nerve defects","volume":"22","author":"Iida","year":"2006","journal-title":"J. Reconstr. Microsurg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/jnr.20982","article-title":"Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury","volume":"84","author":"Glaser","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"012001","DOI":"10.1088\/1748-6041\/7\/1\/012001","article-title":"Injectable hydrogel materials for spinal cord regeneration: A review","volume":"7","author":"Macaya","year":"2012","journal-title":"Biomed. Mater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/neu.1995.12.1","article-title":"A sensitive and reliable locomotor rating scale for open field testing in rats","volume":"12","author":"Basso","year":"1995","journal-title":"J. Neurotrauma"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2481\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:20:18Z","timestamp":1760196018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,22]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["ijms19092481"],"URL":"https:\/\/doi.org\/10.3390\/ijms19092481","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,22]]}}}