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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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Influence of immobilization and sensory re-education on the sensory recovery after reconstruction of digital nerves with direct suture or muscle-in-vein conduits

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Neural Regeneration Research 2016年第2期11卷 338-344页

作者： Theodora Manoli Jennifer Lynn Schiefer Lukas Schulz Thomas Fuchsberger Hans-Eberhard Schaller Department of Hand Plastic and Reconstructive Surgery Burn Unit BG Trauma Center University of Tuebingen

The influence of duration of immobilization and postoperative sensory re-education on the final outcome after reconstruction of digital nerves with direct suture or muscle-in-vein conduits was investigated. The final sensory outcome of 35 patients with 41 digital nerve injuries, who either underwent a direct suture（DS） or a nerve reconstruction with muscle-in-vein conduits（MVC）, was assessed the earliest 12 months postoperatively using static and moving two-point discrimination as well as Semmes-Weinstein monofilaments. There was no significant difference in sensory recovery in cases with an immobilization of 3–7 days versus 10 days in the DS or MVC group. Moreover, no statistically significant difference in sensory recovery was found in cases receiving postoperative sensory re-education versus those not receiving in the DS or MVC group. An early mobilization does not seem to have a negative impact on the final outcome after digital nerve reconstruction. The effect of sensory re-education after digital nerve reconstruction should be reconsidered.

关键词： nerve regeneration peripheral nerve digital nerve sensory re-education immobilization digital direct suture muscle-in-vein conduits

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Regulatory effect and mechanisms of carbon monoxidereleasing molecule Ⅱ on hepatic energy metabolism in septic mice

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World Journal of Gastroenterology 2014年第12期20卷 3301-3311页

作者： Feng Liang Jie Cao Wei-Ting Qin Xu Wang Xue-Feng Qiu Bing-Wei Sun Department of burn and plastic Surgery Affiliated HospitalJiangsu University

AIM: To investigate the possible mechanisms of exogenous carbon monoxide-releasing molecule II (CORM-2) intervention on hepatic energy metabolism in experimental sepsis.

关键词： Sepsis Carbon monoxide Liver Energy metabolism Regulation

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Mechanical tension promotes skin nerve regeneration by upregulating nerve growth factor expression

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Neural Regeneration Research 2013年第17期8卷 1576-1581页

作者： Hu Xiao Dechang Wang Ran Huo Yibing Wang Yongqiang Feng Qiang Li Department of burn and plastic Surgery Shandong Provincial Hospital Affiliated to Shandong University

This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve growth factor by western blot analysis. The results demonstrated that mechanical tension contributed to the formation of a hyperplastic scar in the back skin of rats, in conjunction with increases in both nerve density and nerve growth factor expression in the scar tissue. These experimental findings indicate that the cutaneous nervous system plays a role in hypertrophic scar formation caused by mechanical tension.

关键词： neural regeneration innervation nerve growth factor hypertrophic scar keloid mechanical tension wound healing surgery grants-supported paper neuroregeneration

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MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate burn-Induced Acute Lung Injury in Rats

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Biomedical and Environmental Sciences 2024年第9期37卷 1030-1043页

作者： Zhigang Jia Lin Li Peng Zhao Guo Fei Shuangru Li Qinqin Song Guangpeng Liu Jisong Liu Affiliated Hospital of Jiang nan University Department of Burn and Plastic SurgeryWuxi 214000JiangsuChina The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University Department of Burn and Plastic SurgeryBengbu 230000AnhuiChina

Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage *** Exosomes were isolated from *** burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 ***-eosin staining evaluated inflammatory ***-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1β***-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)*** regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter *** blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and *** analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy *** hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage ***-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted *** miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar *** TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 *** miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.

关键词： Acute lung injury Human umbilical cord mesenchymal stem cell-derived exosomes MicroRNA-451 Tuberous sclerosis complex 1 Mammalian target of rapamycin pathway Autophagy

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Comparison of short- with long-term regeneration results after digital nerve reconstruction with musclein-vein conduits

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Neural Regeneration Research 2015年第10期10卷 1674-1677页

作者： Jennifer Lynn Schiefer Lukas Schulz Rebekka Rath Stéphane Stahl Hans-Eberhard Schaller Theodora Manoli Department of Hand Plastic and Reconstructive Surgery with Burn Center BG Trauma Center University of Tuebingen

Muscle-in-vein conduits are used alternatively to nerve grafts for bridging nerve defects. The purpose of this study was to examine short- and long-term regeneration results after digital nerve reconstruction with muscle-in-vein conduits. Static and moving two-point discriminations and Semmes-Weinstein Monofilaments were used to evaluate sensory recovery 6–12 months and 14–35 months after repair of digital nerves with muscle-in-vein in 7 cases. Both follow-ups were performed after clinical signs of progressing regeneration disappeared. In 4 of 7 cases, a further recovery of both two-point discriminations and in another case of only the static two-point discrimination of 1–3 mm could be found between the short-term and long-term follow-up examination. Moreover, a late recovery of both two-point discriminations was demonstrated in another case. Four of 7 cases showed a sensory improvement by one Semmes-Weinstein Monofilaments. This pilot study suggests that sensory recovery still takes place even when clinical signs of progressing regeneration disappear.

关键词： peripheral nerve regeneration muscle-in-vein conduits digital nerves sensory recovery Semmes-Weinstein two-point discrimination outcome short-term long-term

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Promoting axonal regeneration following nerve surgery： a perspective on ultrasound treatment for nerve injuries

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Neural Regeneration Research 2018年第9期13卷 1530-1533页

作者： Konstantin D. Bergmeister Simeon C. Daeschler Patrick Rhodius Philipp Schoenle Arne Bocker Ulrich Kneser Leila Harhaus Department of Hand Plastic and Reconstructive Surgery Burn Center Department of Plastic and Hand Surgery University of Heidelberg BG Trauma Hospital Ludwigshafen Ludwigshafen Germany

Nerve injury is often associated with limited axonal regeneration and thus leads to delayed or incomplete axonal *** a consequence of slow nerve regeneration,target muscle function is often insufficient and leads to a lifelong ***,the diagnosis of nerve injuries has been improved and likewise surgical reconstruction has undergone significant ***,the problem of slow nerve regeneration has not been *** a recent meta-analysis,we have shown that the application of low-intensity ultrasound promotes nerve regeneration experimentally and thereby can improve functional *** we want to demonstrate the experimental effect of low intensity ultrasound on nerve regeneration,the current state of investigations and its possible future clinical applications.

关键词： peripheral nerve injuries nerve regeneration reinnervation experimental studies low-intensityultrasound adjunct treatment nerve reconstruction nerve surgery axonal injury

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Therapeutic effect of autologous concentrated growth factor on lower-extremity chronic refractory wounds:A case report

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World Journal of Clinical Cases 2021年第18期9卷 4797-4802页

作者： Po Liu Yang Liu Chang-Neng Ke Wei-Shan Li Yue-Ming Liu Shi Xu Department of burn and plastic Surgery Shenzhen Longhua District Central HospitalShenzhen 518110Guangdong ProvinceChina

BACKGROUND Management of chronic refractory wounds is one of the toughest clinical challenges for *** of poor blood supply,less tissue coverage,and easy exposure,the lower leg is a common site for chronic refractory *** current therapeutic regimens often lead to prolonged hospital stay and higher healthcare *** growth factor(CGF)is a novel blood extract that contains various growth factors,platelets,and fibrins to promote wound healing ***,there has been little research reported on the treatment of lower extremity wounds with *** SUMMARY A 37-year-old man,without any past medical history,presented an ulcerated chronic wound on his right lower *** skin defect exhibited clear boundaries,with a size of 2.0 cm×3.5 *** depth of wound was up to the layer of deep *** aureus was detected by bacterial *** final diagnosis was right lower extremity ulcers with ***,silver sulfadiazine,and mupirocin cream were applied to control the *** gel was prepared from the patient’s blood sample,and was used to cover the wound after thorough *** skin wound was successfully healed after three times of CGF *** CGF displays an excellent wound healing promoting effect in patients with lowerextremity chronic refractory wounds.

关键词： Concentrated growth factors Chronic refractory wounds Lower extremity Ulcer Wound healing Case report

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Construction and expression of retroviral vector pLEGFP-N1-TERT in preparation of seed cells for skin tissue engineering

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Asian Pacific Journal of Tropical Medicine 2013年第12期6卷 960-963页

作者： Ting Tan Zhi-Qi Hu Epartment of burn And plastic Surgery Fuzhou General Hospital of Nanjing Command.PLA Department of plastic Surgery Nan fang Hospital of Southern Medical University

Objective:To construct the retroviral vector pLEGFP-N1-telomerase reverse transcriptase(TERT)and to investigate the expression of TERT in neonatal mouse bypodermal ***:The polymerase chain reaction(PCR)-amplified TERT gene was inserted into plasmid *** positive clone was identified by restriction enzyme digestion and sequencing,then was transfected into packaging cells to produce retrovirus *** mouse hypodermal cells were infected with the virus to generate a stable cell *** TERT mRNA expression level,telomerase activity,and enhanced green fluorescent protein(EGFP)expression level were ***:Retroviral vector pLEGFP-N1-TERT was constructed successfully,and a stable cell line of neonatal mouse hypodermal cells expressing EGFP was *** blot and immunohistochemical assay showed that the expression level of TERT was significantly elevated in the neonatal mouse hypodermal ***:A high titer of retrovirus pLEGFP-N1-TERT mediates high-level expression of the exogenous TERT gene in the neonatal mouse hypodermal *** protocol has potential applications for skin tissue engineering and cell transplantation therapy.

关键词： Telomerase reverse transcriptase Retroviral vector Hypodermal cells

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Evaluation of bone remodeling in regard to the age of scaphoid non-unions

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World Journal of Orthopedics 2016年第7期7卷 418-425页

作者： Susanne Rein Uwe Hanisch Hans-Eberhard Schaller Hans Zwipp Stefan Rammelt Stefan Weindel Department of plastic and Hand Surgery Burn UnitTrauma Center Bergmannstrost Center of Orthopaedics and Traumatology University Medicine "Carl Gustav Carus" DresdenTechnicalUniversity Dresden Institute of Pathology "Carl Thiem" Hospital Deptartment of plastic Hand Reconstructive and Burn SurgeryTrauma Center Tuebingen University Deptartment of Hand Aesthetic and Plastic SurgeryHospital of Linth

AIM: To analyse bone remodeling in regard to the age of scaphoid non-unions(SNU) with ***: Thirty-six patients with symptomatic SNU underwent surgery with resection of the pseudarthrosis. The resected material was evaluated histologically after staining with hematoxylin-eosin(HE), tartrate resistant acid phosphatase(TRAP), CD 68, osteocalcin(OC) and osteopontin(OP). Histological examination was performed in a blinded ***: The number of multinuclear osteoclasts in the TRAP-staining correlated with the age of the SNU and was significantly higher in younger SNU(P = 0.034; r = 0.75). A higher number of OP-immunoreactive osteoblasts significantly correlated with a higher number of OC-immunoreactive osteoblasts(P = 0.001; r = 0.55). Furthermore, a greater number of OP-immunoreactive osteoblasts correlated significantly with a higher number of OP-immunoreactive multinuclear osteoclasts(P = 0.008; r = 0.43). SNU older than 6 mo showed a signifi-cant decrease of the number of fibroblasts(P = 0.04). Smoking and the age of the patients had no influence on bone remodeling in ***: Multinuclear osteoclasts showed a significant decrease in relation to the age of SNU. However, most of the immunhistochemical findings of bone remodeling do not correlate with the age of the SNU. This indicates a permanent imbalance of bone formation and resorption as indicated by a concurrent increase in both osteoblast and osteoclast numbers. A clear histological differentiation into phases of bone remodeling in SNU is not possible.

关键词： Bone remodeling Histology Immunohistological staining Scaphoid non-union Scaphoid Wrist joint

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