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The HAL was meant to improve the performance of our artificial nerve guides by giving additional structural and molecular support to regrowing axons. We filled hollow CNGs or two-chambered nerve guides with an inserted longitudinal chitosan film (CNG[F]s), with cell-free HAL or cell-free HA or additionally suspended either na\u00efve Schwann cells (SCs) or fibroblast growth factor 2-overexpressing Schwann cells (FGF2-SCs) within the gels. We subjected female Lewis rats to immediate 15 mm sciatic nerve gap reconstruction and comprehensively compared axonal and functional regeneration parameters with the gold standard autologous nerve graft (ANG) repair. Motor recovery was surveyed by means of electrodiagnostic measurements at 60, 90, and 120 days post-reconstruction. Upon explantation after 120 days, lower limb target muscles were harvested for calculation of muscle-weight ratios. Semi-thin cross-sections of nerve segments distal to the grafts were evaluated histomorphometrically. After 120 days of recovery, only ANG treatment led to full motor recovery. Surprisingly, regeneration outcomes revealed no regeneration-supportive effect of HAL alone and even an impairment of peripheral nerve regeneration when combined with SCs and FGF2-SCs. Furthermore, complementary in vitro studies, conducted to elucidate the reason for this unexpected negative result, revealed that SCs and FGF2-SCs suspended within the hydrogel relatively downregulated gene expression of regeneration-supporting neurotrophic factors. In conclusion, cell-free HAL in its current formulation did not qualify for optimizing regeneration outcome through CNG[F]s. In addition, we demonstrate that our HAL, when used as a carrier system for co-transplanted SCs, changed their gene expression profile and deteriorated the pro-regenerative milieu within the nerve guides.<\/jats:p>","DOI":"10.1177\/0963689720910095","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T02:09:30Z","timestamp":1584324570000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["In Vivo and In Vitro Evaluation of a Novel Hyaluronic Acid\u2013Laminin Hydrogel as Luminal Filler and Carrier System for Genetically Engineered Schwann Cells in Critical Gap Length Tubular Peripheral Nerve Graft in Rats"],"prefix":"10.1177","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3835-7606","authenticated-orcid":false,"given":"Nina","family":"Dietzmeyer","sequence":"first","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"},{"name":"Center for Systems Neuroscience, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"},{"name":"Center for Systems Neuroscience, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Sch\u00fcning","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"},{"name":"Center for Systems Neuroscience, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Rochkind","sequence":"additional","affiliation":[{"name":"Research Center for Nerve Reconstruction, Department of Neurosurgery, Tel-Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Almog","sequence":"additional","affiliation":[{"name":"Research Center for Nerve Reconstruction, Department of Neurosurgery, Tel-Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Nevo","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"},{"name":"Prof. Nevo passed away"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Lieke","sequence":"additional","affiliation":[{"name":"Transplant Laboratory, Department of General-, Visceral-, and Transplantation Surgery, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Kankowski","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Haastert-Talini","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"},{"name":"Center for Systems Neuroscience, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,3,15]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000197900"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-199807000-00025"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/2000656X.2010.542654"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.10.002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/698256"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2011.0438"},{"issue":"8","key":"e_1_3_3_8_2","first-page":"1421","article-title":"Modification of tubular chitosan-based peripheral nerve implants \u2013 applications for simple or more complex approaches","volume":"15","author":"Dietzmeyer N","year":"2019","unstructured":"Dietzmeyer N, F\u00f6rthmann M, Grothe C, Haastert-Talini K. 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