{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:53:38Z","timestamp":1782982418878,"version":"3.54.5"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RedDress Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>This preliminary study aimed to investigate an ActiGraft blood clot implant (RedDress Ltd., Pardes-Hanna, Israel) attempting to treat and induce the regeneration of a completely injured peripheral nerve with a massive loss defect. The tibial portion of the sciatic nerve in 11 rabbits was transected, and a 25 mm nerve gap was reconnected using a collagen tube. A comparison was performed between the treatment group (eight rabbits; reconnection using a tube filled with ActiGraft blood clot) and the control group (three rabbits; gap reconnection using an empty tube). The post-operative follow-up period lasted 18 weeks and included electrophysiological and histochemical assessments. The pathological severity score was high in the tube cross sections of the control group (1.33) compared to the ActiGraft blood clot treatment group (0.63). Morphometric analysis showed a higher percentage of the positive myelin basic protein (MBP) stained area in the ActiGraft blood clot group (19.57%) versus the control group (3.67%). These differences were not statistically significant due to the small group sizes and the large intra-group variability. The results of this preliminary study suggest that the application of an ActiGraft blood clot (into the collagen tube) can enable nerve recovery. However, a future study using a larger animal group is required to achieve objective statistical results.<\/jats:p>","DOI":"10.3390\/bioengineering11040298","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T05:10:53Z","timestamp":1711084253000},"page":"298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nerve Reconstruction Using ActiGraft Blood Clot in Rabbit Acute Peripheral Injury Model: Preliminary Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9590-9764","authenticated-orcid":false,"given":"Shimon","family":"Rochkind","sequence":"first","affiliation":[{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Sirota","sequence":"additional","affiliation":[{"name":"RedDress Ltd., Pardes Hana 3701142, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alon","family":"Kushnir","sequence":"additional","affiliation":[{"name":"RedDress Ltd., Pardes Hana 3701142, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/(SICI)1097-4598(200006)23:6<863::AID-MUS4>3.0.CO;2-0","article-title":"Traumatic injury to peripheral nerves","volume":"23","author":"Robinson","year":"2000","journal-title":"Muscle Nerve"},{"key":"ref_2","unstructured":"Hammi, C., and Yeung, B. (2023). StatPearls, StatPearls."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/1097-4598(200103)24:3<311::AID-MUS1001>3.0.CO;2-A","article-title":"Clinical spectrum of chronic acquired demyelinating polyneuropathies","volume":"24","author":"Saperstein","year":"2001","journal-title":"Muscle Nerve"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1212\/WNL.55.7.915","article-title":"Pharmacologic treatment of pain in polyneuropathy","volume":"55","author":"Sindrup","year":"2000","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"217","DOI":"10.4103\/0971-3026.137025","article-title":"Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications","volume":"24","author":"Chhabra","year":"2014","journal-title":"Indian J. Radiol. Imaging"},{"key":"ref_6","first-page":"167","article-title":"Anatomy and physiology of peripheral nerve injury and repair","volume":"29","author":"Flores","year":"2000","journal-title":"Am. J. Orthop."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.main.2011.04.010","article-title":"Gunshot injuries to the nerves","volume":"30","author":"Oberlin","year":"2011","journal-title":"Chir. Main"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1179\/016164104225013743","article-title":"A review of research endeavors to optimize peripheral nerve reconstruction","volume":"26","author":"Myckatyn","year":"2004","journal-title":"Neurol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00590-018-2344-2","article-title":"Current concepts in peripheral nerve surgery","volume":"29","author":"Beris","year":"2019","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.jcot.2019.08.003","article-title":"Management of peripheral nerve injury","volume":"10","author":"Bhandari","year":"2019","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3928\/01477447-20161019-01","article-title":"The present and future for peripheral nerve regeneration","volume":"40","author":"Panagopoulos","year":"2017","journal-title":"Orthopedics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1701713","DOI":"10.1002\/adfm.201701713","article-title":"Tissue-engineered peripheral nerve interfaces","volume":"28","author":"Spearman","year":"2018","journal-title":"Adv. Funct. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0749-0712(21)00503-5","article-title":"Techniques for nerve grafting","volume":"16","author":"Millesi","year":"2000","journal-title":"Hand Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.pneurobio.2010.10.002","article-title":"Repairing injured peripheral nerves: Bridging the gap","volume":"92","author":"Deumens","year":"2010","journal-title":"Prog. Neurob\u0131ol."},{"key":"ref_15","unstructured":"Stefano, G., Pierluigi, T., and Bruno, B. (2009). International Review of Neurobiology, Academic Press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.injury.2010.12.030","article-title":"FDA approved guidance conduits and wraps for peripheral nerve injury: A review of materials and efficacy","volume":"43","author":"Kehoe","year":"2012","journal-title":"Injury"},{"key":"ref_17","first-page":"554","article-title":"Ueber Transplantation, Regeneration und entz\u00fcndliche Neubildung","volume":"18","author":"Gluck","year":"1881","journal-title":"Klin. Wochenschr."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Snyder, R.J., Schultz, G., Wachuku, C., Arij, M., Rashid, A.M., and Ead, J.K. (2023). Proposed Mechanism of Action of Topically Applied Autologous Blood Clot Tissue. A Quintessential Cellular and Tissue-Based Therapy. J. Am. Podiatr. Med. Assoc., 113.","DOI":"10.7547\/20-140"},{"key":"ref_19","first-page":"317","article-title":"Efficacy and safety of a novel autologous wound matrix in the management of complicated, chronic wounds: A pilot study","volume":"28","author":"Kushnir","year":"2016","journal-title":"Wounds"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1177\/039139880402700208","article-title":"Fibrin\/Schwann cell matrix in poly-epsilon-caprolactone conduits enhances guided nerve regeneration","volume":"27","author":"Galla","year":"2004","journal-title":"Int. J. Artif. Organs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/micr.20154","article-title":"Autologous fibrin glue in peripheral nerve regeneration in vivo","volume":"25","author":"Choi","year":"2005","journal-title":"Microsurgery"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.ijom.2016.06.003","article-title":"The effect of a platelet-rich fibrin conduit on neurosensory recovery following inferior alveolar nerve lateralization: A preliminary clinical study","volume":"45","author":"Khojasteh","year":"2016","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1055\/s-0037-1603355","article-title":"Platelet-rich fibrin conduits as an alternative to nerve autografts for peripheralnerve repair","volume":"33","author":"Roth","year":"2017","journal-title":"J. Reconstr. Microsurg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1089\/ten.tea.2017.0457","article-title":"An optimized collagen-fibrin blend engineered neural tissue promotes peripheral nerve repair","volume":"24","author":"Schuh","year":"2018","journal-title":"Tissue Eng. Part A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"026022","DOI":"10.1088\/1741-2560\/10\/2\/026022","article-title":"Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration","volume":"10","author":"Carriel","year":"2013","journal-title":"J. Neural. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3389\/fncel.2018.00501","article-title":"In vivo evaluation of nanostructured fibrin-agarose hydrogels with mesenchymal stem cells for peripheral nerve repair","volume":"12","author":"Campos","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.actbio.2017.04.010","article-title":"Prompt peripheral nerve regeneration induced by a hierarchically aligned fibrin nanofiber hydrogel","volume":"55","author":"Du","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1055\/s-0042-1747959","article-title":"A Rabbit Model for Peripheral Nerve Reconstruction Studies Avoiding Automutilation Behavior","volume":"17","author":"Sorkin","year":"2022","journal-title":"J. Brachial. Plex. Peripher. Nerve Inj."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1177\/0192623318761348","article-title":"Use of Severity Grades to characterize Histopathologic Changes","volume":"46","author":"Schafer","year":"2018","journal-title":"Toxicol. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.expneurol.2008.04.012","article-title":"The impact of motor and sensory nerve architecture on nerve regeneration","volume":"212","author":"Moradzadeh","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_31","first-page":"3515","article-title":"Peripheral nerve regeneration: An opinion on channels, scaffolds and anisotropy","volume":"27","author":"Bellamkonda","year":"2006","journal-title":"Biomaterials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0074-7742(09)87011-6","article-title":"Chapter 11: Tissue engineering of peripheral nerves","volume":"87","author":"Battiston","year":"2009","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.biomaterials.2007.08.045","article-title":"Differences between the effect of anisotropic and isotropic laminin and nerve growth factor presenting scaffolds on nerve regeneration across long peripheral nerve gaps","volume":"29","author":"Dodla","year":"2008","journal-title":"Biomaterials"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0074-7742(09)87010-4","article-title":"Chapter 10: Conduit luminal additives for peripheral nerve repair","volume":"87","author":"Yan","year":"2009","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1006\/exnr.1999.7095","article-title":"Guided neurite elongation and Schwann cell invasion into magnetically aligned collagen in simulated peripheral nerve regeneration","volume":"158","author":"Dubey","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1114\/1.1626118","article-title":"Rational design of contact guiding, neurotrophic matrices for peripheral nerve regeneration","volume":"31","author":"Rosner","year":"2003","journal-title":"Ann. Biomed. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1097\/MOT.0000000000000812","article-title":"The past the present and the future of face transplantation","volume":"25","author":"Siemionow","year":"2020","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.bioeng.5.011303.120731","article-title":"Neural tissue engineering: Strategies for repair and regeneration","volume":"5","author":"Schmidt","year":"2003","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1179\/016164104225013905","article-title":"Further development of reconstructive and cell tissue-engineering technology for treatment of complete peripheral nerve injury in rats","volume":"26","author":"Rochkind","year":"2004","journal-title":"Neurol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rochkind, S., and Nevo, Z. (2014). Recovery of Peripheral Nerve with Massive Loss Defect by Tissue Engineered Guiding Regenerative Gel. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/327578"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"609638","DOI":"10.3389\/fsurg.2020.609638","article-title":"Reviving Matrix for Nerve Reconstruction in Rabbit model of chronic peripheral nerve injury with massive loss defect","volume":"7","author":"Rochkind","year":"2021","journal-title":"Front. Surg."},{"key":"ref_42","first-page":"1","article-title":"Photobiomodulation therapy (PBMT) utilizes visible and near-infrared electromagnetic energy to induce therapeutic photochemical changes and improve clinical recovery outcomes","volume":"42","author":"Fellin","year":"2024","journal-title":"Photobiomodul. Photomed. Laser Surg."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Rosso, M.P.d.O., Buchaim, D.V., Kawano, N., Furlanette, G., Pomini, K.T., and Buchaim, R.L. (2018). Photobiomodulation Therapy (PBMT) in Peripheral Nerve Regeneration: A Systematic Review. Bioengineering, 5.","DOI":"10.3390\/bioengineering5020044"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1179\/016164104225013914","article-title":"Phototherapy promotes regeneration and functionalrecovery of injured peripheral nerve","volume":"26","author":"Anders","year":"2004","journal-title":"Neurol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/mus.20305","article-title":"Phototherapy for enhancing peripheral nerve repair: A review of the literature","volume":"31","author":"Geuna","year":"2005","journal-title":"Muscle Nerve"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0074-7742(09)87025-6","article-title":"Chapter 25 Phototherapy in Peripheral Nerve Injury: Effects on Muscle Preservation and Nerve Regeneration","volume":"87","author":"Rochkind","year":"2009","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1089\/pho.2007.2076","article-title":"Efficacy of 780-nm laser phototherapy on peripheral nerve regeneration after neurotube reconstruction procedure (double-blind randomized study)","volume":"25","author":"Rochkind","year":"2007","journal-title":"Photomed. Laser Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/jbm.a.34314","article-title":"Effects of large-area irradiated laser phototherapy on peripheral nerve regeneration across a large gap in a biomaterial conduit","volume":"101","author":"Shen","year":"2013","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.clindermatol.2004.07.020","article-title":"Treatment of nonhealing ulcers with allografts","volume":"23","author":"Snyder","year":"2005","journal-title":"Clin Dermato."},{"key":"ref_50","first-page":"205","article-title":"Safety and Efficacy of an Autologous Blood Clot Product in the Management of Texas 1A or 2A Neuropathic Diabetic Foot Ulcers: A Prospective, Multicenter, Open Label Pilot Study","volume":"30","author":"Snyder","year":"2018","journal-title":"Wounds"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gao, H., You, Y., Zhang, G., Zhao, F., Sha, Z., and Shen, Y. (2013). The use of fiber-reinforced scaffolds cocultured with Schwann cells and vascular endothelial cells to repair rabbit sciatic nerve defect with vascularization. Biomed. Res. Int., 2013.","DOI":"10.1155\/2013\/362918"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1179\/016164104225013752","article-title":"Bridging peripheral nerve defects with muscle-vein combined guides","volume":"26","author":"Geuna","year":"2004","journal-title":"Neurol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1016\/j.biomaterials.2011.01.065","article-title":"Peripheral nerve regeneration using a microporous polylactic acid asymmetric conduit in a rabbit long-gap sciatic nerve transection model","volume":"32","author":"Hsu","year":"2011","journal-title":"Biomaterials"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/11\/4\/298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:17:51Z","timestamp":1760105871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/11\/4\/298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":53,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["bioengineering11040298"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering11040298","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]}}}