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Li YX, Zhao LM, Zhang XZ, Ma XK, Liang JQ, Gan TJ, Gong H, Jiang YL, Wu Y, Song YT, Zhang Y, Li Y, Chen XT, Xu CH, Ouyang XY, Li-Ling J, Zhang H, Xie HQ. Smooth muscle extracellular matrix modified small intestinal submucosa conduits promote peripheral nerve repair. Biomaterials 2025; 321:123346. [PMID: 40253732 DOI: 10.1016/j.biomaterials.2025.123346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/10/2025] [Accepted: 04/13/2025] [Indexed: 04/22/2025]
Abstract
Challenges still exist to develop an ideal cell-free nerve guidance conduit (NGC) providing a favorable microenvironment for rapid and successful nerve regeneration. Proteomic analysis revealed that extracellular matrix (ECM) derived from smooth muscle cells (SMCs) was abundant in nerve-related active proteins and significantly enriched signaling pathways involved in nerve regeneration. However, whether NGCs based on SMCs-derived ECM modification strategy promote nerve regeneration remains unclear. In the study, we investigated the neuroregenerative effect of SMCs-derived ECM and developed a novel NGC (MyoNerve) by coating small intestinal submucosa (SIS) with SMCs-derived ECM. The SMCs-ECM was rich in neurotrophic factors, which endowed MyoNerve with remarkable neuroregenerative capabilities by promoting the expression of genes implicated in aspects of neuronal maintenance and activating signaling pathways involved in nerve regeneration. In vitro, MyoNerve exhibited excellent bioactivity for accelerating angiogenesis, regulating macrophages polarization, promoting the proliferation, migration and elongation of Schwann cells, enhancing differentiation of PC12 cells, and inducing the neurite outgrowth of dorsal root ganglia. In the model of rat sciatic nerve 10 mm defect, MyoNerve showed great potential for functional nerve regeneration by promoting angiogenesis, proliferation and migration of Schwann cells and neuron, axonal regeneration, remyelination, and neurological functional recovery.
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Affiliation(s)
- Ya-Xing Li
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Long-Mei Zhao
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Xiu-Zhen Zhang
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Xi-Kun Ma
- Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University Chengdu, Sichuan, 610041, China
| | - Jing-Qi Liang
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ting-Jiang Gan
- Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University Chengdu, Sichuan, 610041, China
| | - Heng Gong
- Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University Chengdu, Sichuan, 610041, China
| | - Yan-Lin Jiang
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ye Wu
- Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University Chengdu, Sichuan, 610041, China
| | - Yu-Ting Song
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yi Zhang
- Core Facilities of West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yue Li
- Core Facilities of West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiao-Ting Chen
- Animal Experimental Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Cong-Hui Xu
- Department of Radiology, Chengdu Shangjin Nanfu Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiang-Yu Ouyang
- Department of Orthopedics, Hospital of Chengdu Office of People's Government of Xizang Autonomous Region, Chengdu, Sichuan, 610041, China
| | - Jesse Li-Ling
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Hui Zhang
- Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University Chengdu, Sichuan, 610041, China.
| | - Hui-Qi Xie
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
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Su S, Wang J. A Comprehensive Review on Bioprinted Graphene-Based Material (GBM)-Enhanced Scaffolds for Nerve Guidance Conduits. Biomimetics (Basel) 2025; 10:213. [PMID: 40277612 PMCID: PMC12024949 DOI: 10.3390/biomimetics10040213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 03/21/2025] [Accepted: 03/27/2025] [Indexed: 04/26/2025] Open
Abstract
Peripheral nerve injuries (PNIs) pose significant challenges to recovery, often resulting in impaired function and quality of life. To address these challenges, nerve guidance conduits (NGCs) are being developed as effective strategies to promote nerve regeneration by providing a supportive framework that guides axonal growth and facilitates reconnection of severed nerves. Among the materials being explored, graphene-based materials (GBMs) have emerged as promising candidates due to their unique properties. Their unique properties-such as high mechanical strength, excellent electrical conductivity, and favorable biocompatibility-make them ideal for applications in nerve repair. The integration of 3D printing technologies further enhances the development of GBM-based NGCs, enabling the creation of scaffolds with complex architectures and precise topographical cues that closely mimic the natural neural environment. This customization significantly increases the potential for successful nerve repair. This review offers a comprehensive overview of properties of GBMs, the principles of 3D printing, and key design strategies for 3D-printed NGCs. Additionally, it discusses future perspectives and research directions that could advance the application of 3D-printed GBMs in nerve regeneration therapies.
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Affiliation(s)
- Siheng Su
- Department of Mechanical Engineering, California State University, Fullerton, CA 92831, USA
| | - Jilong Wang
- Key Laboratory of Clean Dyeing and Finishing Technology of Zhejiang Province, College of Textile and Garment, Shaoxing University, Shaoxing 312000, China
- Shaoxing Sub-Center of National Engineering Research Center for Fiber-Based Composites, Shaoxing University, Shaoxing 312000, China
- Shaoxing Key Laboratory of High Performance Fibers & Products, Shaoxing University, Shaoxing 312000, China
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Kalmar CL, Margulies IG, Sergesketter AR. PRS Journal Club: Reinforcement of Fundamental Concepts in Hand Surgery. Plast Reconstr Surg 2025; 155:587-588. [PMID: 39999239 DOI: 10.1097/prs.0000000000011904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2025]
Affiliation(s)
| | - Ilana G Margulies
- Department of Plastic Surgery, MedStar Georgetown University Hospital
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Hu K, Williams MCG, Kammien AJ, Canner J, Mukherjee T, Hill E, Colen D. Cost Comparison of Digital Nerve Repair Techniques. Plast Reconstr Surg 2025; 155:543e-552e. [PMID: 39085087 DOI: 10.1097/prs.0000000000011662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
BACKGROUND Direct cost comparisons of nerve allograft with other techniques for repairing short digital nerve gaps are lacking. This study compares the costs of various techniques for digital nerve repair, anticipating significant cost increases for allograft implants. METHODS The State Ambulatory Surgery and Services Databases for Florida, New York, and Wisconsin from 2015 through 2020 were used. Patients with primary repair, short autograft, conduit, and allograft were compared along total, surgical supply, operating room, and anesthesia charges. RESULTS Among 5009 patients, there were 2967 primary nerve repairs (59.2%), 77 autografts (1.5%), 1647 conduits (32.9%), and 318 allografts (6.3%). A total of 2886 patients were male (57.6%), and the mean patient age was 40.4 ± 16.3 years. Over the study period, primary repairs decreased (from 63.9% in 2015 to 56.3% in 2020), whereas allografts increased significantly (from 8.8% in 2018 to 12.6% in 2020). Median total charges varied significantly across procedures, with the most expensive being allograft ($35,295), followed by conduit ($25,717), autograft ($24,749), and primary repair ($18,767). On multivariable regression, allografts were significantly more expensive than autografts in total charges of $11,224 (95% CI, $4196 to $18,252) and supply charges of $10,484 (95% CI, $6073 to $14,896), but not in operating room or anesthesia charges. Flexor tendon repair was associated with greater total, operating room, and anesthesia charges, but had similar supply charges. CONCLUSIONS Nerve allografting is the most expensive digital nerve repair technique, most likely due to the cost of the implant. To minimize health care expenditure and ensure equitable patient access, surgeons should consider this cost along with clinical factors when choosing digital nerve repair techniques.
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Affiliation(s)
- Kevin Hu
- From the Division of Plastic and Reconstructive Surgery
| | | | | | | | | | - Elspeth Hill
- From the Division of Plastic and Reconstructive Surgery
| | - David Colen
- From the Division of Plastic and Reconstructive Surgery
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Tusnim J, Kutuzov P, Grasman JM. In Vitro Models for Peripheral Nerve Regeneration. Adv Healthc Mater 2024; 13:e2401605. [PMID: 39324286 DOI: 10.1002/adhm.202401605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 08/14/2024] [Indexed: 09/27/2024]
Abstract
Peripheral nerve injury (PNI) resulting in lesions is highly prevalent clinically, but current therapeutic approaches fail to provide satisfactory outcomes in many patients. While peripheral nerves have intrinsic regenerative capacity, the regenerative capabilities of peripheral nerves are often insufficient to restore full functionality. This highlights an unmet need for developing more effective strategies to repair damaged peripheral nerves and improve regenerative success. Consequently, researchers are actively exploring a variety of therapeutic strategies, encompassing the local delivery of trophic factors or bioactive molecules, the design of advanced biomaterials that interact with regenerating axons, and augmentation with nerve guidance conduits or complex prostheses. However, clinical translation of these technologies remains limited, emphasizing the need for continued research on peripheral nerve regeneration modalities that can enhance functional restoration. Experimental models that accurately recapitulate key aspects of peripheral nerve injury and repair biology can accelerate therapeutic development by enabling systematic testing of new techniques. Advancing regenerative therapies for PNI requires bridging the gap between basic science discoveries and clinical application. This review discusses different in vitro models of peripheral nerve injury and repair, including their advantages, limitations, and potential applications.
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Affiliation(s)
- Jarin Tusnim
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Peter Kutuzov
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Jonathan M Grasman
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
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Van Gheem J, Rounds A, Blackwood T, Cox C, Hernandez EJ, McKee D, MacKay B. Case Series of Traumatic Peripheral Nerve Injuries in Pediatric Patients Treated with Allograft Repair. JOURNAL OF HAND SURGERY GLOBAL ONLINE 2024; 6:801-807. [PMID: 39703582 PMCID: PMC11652274 DOI: 10.1016/j.jhsg.2024.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 05/14/2024] [Indexed: 12/21/2024] Open
Abstract
Purpose In the adult literature, allograft reconstruction of gapped peripheral nerve injuries has gained popularity over autologous nerve grafting. Allografts have demonstrated similar recovery while eliminating donor site morbidity. There is no well-defined incidence or treatment of such injuries in children. Our study explores the epidemiology and outcomes of traumatic pediatric peripheral nerve injuries treated with allograft. Methods This is a retrospective case series of a prospectively maintained database of all pediatric patients who underwent nerve allograft reconstruction at a Level I trauma center between September 2011 and July 2021. Results We identified 24 allograft nerve reconstructions in 18 patients, average age 12.9 years (range 1.5-17.0) and 78% male. Five patients (28%) were injured in a motor vehicle accident, and four were injured by sharp laceration, machinery, and blast injury (22%). The most injured nerve was digital (n = 10, 42%) followed by 8 (33%) ulnar, and 4 (17%) median. The average gap length was 30.3 ± 23.8 mm (range 4-87 mm). Fifteen nerves were repaired within 24 hours (63%). Average follow-up was 13.7 ± 14.5 months (range 1.6-46.8 months). At final follow-up, 9 (38%) had full sensory recovery, 6 (25%) protective sensation, 2 (8%) deep pressure, and 1 (4%) no sensation but a positive Tinel's sign. Conclusions Allograft reconstruction is a viable option for the treatment of traumatic pediatric peripheral nerve injuries with gaps not amenable to direct repair. Type of study/level of evidence Therapeutic IV.
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Affiliation(s)
- Jacqueline Van Gheem
- Department of Orthopedic Surgery, Texas Tech University of Health Sciences Center, Lubbock, TX
| | - Alexis Rounds
- Department of Orthopedic Surgery, Texas Tech University of Health Sciences Center, Lubbock, TX
| | - Taylor Blackwood
- Department of Orthopedic Surgery, Texas Tech University of Health Sciences Center, Lubbock, TX
| | - Cameron Cox
- Department of Orthopedic Surgery, Texas Tech University of Health Sciences Center, Lubbock, TX
| | - Evan J. Hernandez
- Department of Orthopedic Surgery, Texas Tech University of Health Sciences Center, Lubbock, TX
| | - Desirae McKee
- Department of Orthopedic Surgery, Texas Tech University of Health Sciences Center, Lubbock, TX
| | - Brendan MacKay
- Department of Orthopedic Surgery, Texas Tech University of Health Sciences Center, Lubbock, TX
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Yu JL, Cordero DM, Miller EA. Principles of microvascular surgery in the upper extremity. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY & TRAUMATOLOGY : ORTHOPEDIE TRAUMATOLOGIE 2024; 34:3647-3659. [PMID: 37875649 DOI: 10.1007/s00590-023-03749-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 09/25/2023] [Indexed: 10/26/2023]
Abstract
Upper extremity replantation and microsurgery can be challenging even for the experienced hand and upper extremity surgeon and requires thoughtful consideration and evaluation. This review aims to discuss the general considerations in upper extremity replantation management from the preoperative through the postoperative period.
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Affiliation(s)
- Jenny L Yu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Washington, 325 9th Ave. Mailstop 359796, Seattle, WA, 98104, USA
| | - Daniella M Cordero
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Washington, 325 9th Ave. Mailstop 359796, Seattle, WA, 98104, USA
| | - Erin A Miller
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Washington, 325 9th Ave. Mailstop 359796, Seattle, WA, 98104, USA.
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DeMartini S, Faust A, Navarro B, Dy CJ. Psychological Aspects of Nerve Gap Reconstruction: Addressing Patient Perspectives and Expectations. JOURNAL OF HAND SURGERY GLOBAL ONLINE 2024; 6:760-765. [PMID: 39381399 PMCID: PMC11457534 DOI: 10.1016/j.jhsg.2024.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Purpose Preoperative expectations play a major role in determining patient satisfaction after surgery. The aim of this study was to characterize patient's preoperative expectations and postoperative perceptions of nerve gap repair surgery. Methods We conducted a search of Embase, Scopus, and Web of Science databases for peer-reviewed articles that studied patient expectations, perceptions, and impressions of nerve gap repair in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies related to lumbar plexus radiculopathy, reimplantation, or patient satisfaction scores without patient testimony were excluded. Primary and secondary outcomes were patient's preoperative expectations and postoperative perceptions of nerve gap repair surgery, respectively. Results We included 11 studies evaluating a total of 462 patients. One study evaluated only patient expectations, six studies evaluated only patient perspectives, and four studies evaluated both. Patients were generally overly optimistic in their expectations of surgery. Postoperative satisfaction ranged from 82% to 86%, and 81% to 87% of patients would choose to undergo their surgery again knowing what they know now. Conclusions Patient expectations in nerve gap repair are optimistic, and at times unrealistic. Patient satisfaction with nerve gap repair is high and subject to influence from preoperative education and postoperative outcomes of functional and sensory recovery. Clinical relevance Surgeons should be aware that patient expectations of their postoperative outcomes can have substantial impacts on their perceived management and overall satisfaction. More emphasis should be placed on preoperative education and expectation management to optimize patient satisfaction.
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Affiliation(s)
- Stephen DeMartini
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO
| | - Amanda Faust
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO
| | - Brendan Navarro
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO
| | - Christopher J. Dy
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO
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Zou XF, Zhang BZ, Qian WW, Cheng FM. Bone marrow mesenchymal stem cells in treatment of peripheral nerve injury. World J Stem Cells 2024; 16:799-810. [PMID: 39219723 PMCID: PMC11362854 DOI: 10.4252/wjsc.v16.i8.799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 05/20/2024] [Accepted: 08/05/2024] [Indexed: 08/26/2024] Open
Abstract
Peripheral nerve injury (PNI) is a common neurological disorder and complete functional recovery is difficult to achieve. In recent years, bone marrow mesenchymal stem cells (BMSCs) have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous transplantation ability. This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI. The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury. BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors, extracellular matrix molecules, and adhesion molecules. Additionally, BMSCs release pro-angiogenic factors to promote the formation of new blood vessels. They modulate cytokine expression and regulate macrophage polarization, leading to immunomodulation. Furthermore, BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration, thereby promoting neuronal repair and regeneration. Moreover, this review explores methods of applying BMSCs in PNI treatment, including direct cell transplantation into the injured neural tissue, implantation of BMSCs into nerve conduits providing support, and the application of genetically modified BMSCs, among others. These findings confirm the potential of BMSCs in treating PNI. However, with the development of this field, it is crucial to address issues related to BMSC therapy, including establishing standards for extracting, identifying, and cultivating BMSCs, as well as selecting application methods for BMSCs in PNI such as direct transplantation, tissue engineering, and genetic engineering. Addressing these issues will help translate current preclinical research results into clinical practice, providing new and effective treatment strategies for patients with PNI.
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Affiliation(s)
- Xiong-Fei Zou
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing 100730, China
| | - Bao-Zhong Zhang
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
| | - Wen-Wei Qian
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Beijing 100730, China
| | - Florence Mei Cheng
- College of Nursing, The Ohio State University, Ohio, OH 43210, United States
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Kong L, Gao X, Yao X, Xie H, Kang Q, Sun W, You Z, Qian Y, Fan C. Multilevel neurium-mimetic individualized graft via additive manufacturing for efficient tissue repair. Nat Commun 2024; 15:6428. [PMID: 39079956 PMCID: PMC11289102 DOI: 10.1038/s41467-024-49980-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 06/24/2024] [Indexed: 08/02/2024] Open
Abstract
Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine.
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Affiliation(s)
- Lingchi Kong
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China
| | - Xin Gao
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Research Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society), Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, 201620, Shanghai, China
| | - Xiangyun Yao
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, 201306, Shanghai, China
| | - Haijiao Xie
- Hangzhou Yanqu Information Technology Co.Ltd., 310003, Hangzhou, China
| | - Qinglin Kang
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China
| | - Wei Sun
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Research Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society), Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, 201620, Shanghai, China.
| | - Zhengwei You
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Research Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society), Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, 201620, Shanghai, China.
| | - Yun Qian
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China.
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, 201306, Shanghai, China.
| | - Cunyi Fan
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China.
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, 201306, Shanghai, China.
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Mao X, Li T, Cheng J, Tao M, Li Z, Ma Y, Javed R, Bao J, Liang F, Guo W, Tian X, Fan J, Yu T, Ao Q. Nerve ECM and PLA-PCL based electrospun bilayer nerve conduit for nerve regeneration. Front Bioeng Biotechnol 2023; 11:1103435. [PMID: 36937756 PMCID: PMC10017983 DOI: 10.3389/fbioe.2023.1103435] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 02/16/2023] [Indexed: 03/06/2023] Open
Abstract
Introduction: The porcine nerve-derived extracellular matrix (ECM) fabricated as films has good performance in peripheral nerve regeneration. However, when constructed as conduits to bridge nerve defects, ECM lacks sufficient mechanical strength. Methods: In this study, a novel electrospun bilayer-structured nerve conduit (BNC) with outer poly (L-lactic acid-co-ε-caprolactone) (PLA-PCL) and inner ECM was fabricated for nerve regeneration. The composition, structure, and mechanical strength of BNC were characterized. Then BNC biosafety was evaluated by cytotoxicity, subcutaneous implantation, and cell affinity tests. Furthermore, BNC was used to bridge 10-mm rat sciatic nerve defect, and nerve functional recovery was assessed by walking track, electrophysiology, and histomorphology analyses. Results: Our results demonstrate that BNC has a network of nanofibers and retains some bioactive molecules, including collagen I, collagen IV, laminin, fibronectin, glycosaminoglycans, nerve growth factor, and brain-derived neurotrophic factor. Biomechanical analysis proves that PLA-PCL improves the BNC mechanical properties, compared with single ECM conduit (ENC). The functional evaluation of in vivo results indicated that BNC is more effective in nerve regeneration than PLA-PCL conduit or ENC. Discussion: In conclusion, BNC not only retains the good biocompatibility and bioactivity of ECM, but also obtains the appropriate mechanical strength from PLA-PCL, which has great potential for clinical repair of nerve defects.
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Affiliation(s)
- Xiaoyan Mao
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Ting Li
- Department of Tissue Engineering, China Medical University, Shenyang, China
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Junqiu Cheng
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Meihan Tao
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Zhiyuan Li
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Yizhan Ma
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Rabia Javed
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Jie Bao
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Fang Liang
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Weihong Guo
- Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohong Tian
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Jun Fan
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Tianhao Yu
- Liaoning Provincial Key Laboratory of Oral Diseases, The VIP Department, School and Hospital of Stomatology, China Medical University, Shenyang, China
| | - Qiang Ao
- Department of Tissue Engineering, China Medical University, Shenyang, China
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
- Institute of Regulatory Science for Medical Device, Sichuan University, Chengdu, China
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Talukder MAH, Elfar J, Lee J, Karuman Z, Gurjar A, Govindappa P, Guddadarangaiah J, Manto K, Wandling G, Hegarty J, Waning D. Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice: effects of 4-aminopyridine. Neural Regen Res 2023; 18:439-444. [PMID: 35900443 PMCID: PMC9396510 DOI: 10.4103/1673-5374.346456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
We recently demonstrated a repurposing beneficial effect of 4-aminopyridine (4-AP), a potassium channel blocker, on functional recovery and muscle atrophy after sciatic nerve crush injury in rodents. However, this effect of 4-AP is unknown in nerve transection, gap, and grafting models. To evaluate and compare the functional recovery, nerve morphology, and muscle atrophy, we used a novel stepwise nerve transection with gluing (STG), as well as 7-mm irreparable nerve gap (G-7/0) and 7-mm isografting in 5-mm gap (G-5/7) models in the absence and presence of 4-AP treatment. Following surgery, sciatic functional index was determined weekly to evaluate the direct in vivo global motor functional recovery. After 12 weeks, nerves were processed for whole-mount immunofluorescence imaging, and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber cross-sectional area and minimal Feret’s diameter. Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model. 4-AP did not affect the sciatic functional index recovery in any model. Compared to STG, nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting. While muscle weight, cross-sectional area, and minimal Feret’s diameter were significantly smaller in G-7/0 model compared with STG and G-5/7, 4-AP treatment significantly increased right TA muscle mass, cross-sectional area, and minimal Feret’s diameter in G-7/0 model. These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap, and 4-AP exerts differential effects on functional recovery and muscle atrophy.
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13
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Kong L, Gao X, Qian Y, Sun W, You Z, Fan C. Biomechanical microenvironment in peripheral nerve regeneration: from pathophysiological understanding to tissue engineering development. Am J Cancer Res 2022; 12:4993-5014. [PMID: 35836812 PMCID: PMC9274750 DOI: 10.7150/thno.74571] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 06/11/2022] [Indexed: 01/12/2023] Open
Abstract
Peripheral nerve injury (PNI) caused by trauma, chronic disease and other factors may lead to partial or complete loss of sensory, motor and autonomic functions, as well as neuropathic pain. Biological activities are always accompanied by mechanical stimulation, and biomechanical microenvironmental homeostasis plays a complicated role in tissue repair and regeneration. Recent studies have focused on the effects of biomechanical microenvironment on peripheral nervous system development and function maintenance, as well as neural regrowth following PNI. For example, biomechanical factors-induced cluster gene expression changes contribute to formation of peripheral nerve structure and maintenance of physiological function. In addition, extracellular matrix and cell responses to biomechanical microenvironment alterations after PNI directly trigger a series of cascades for the well-organized peripheral nerve regeneration (PNR) process, where cell adhesion molecules, cytoskeletons and mechanically gated ion channels serve as mechanosensitive units, mechanical effector including focal adhesion kinase (FAK) and yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) as mechanotransduction elements. With the rapid development of tissue engineering techniques, a substantial number of PNR strategies such as aligned nerve guidance conduits, three-dimensional topological designs and piezoelectric scaffolds emerge expected to improve the neural biomechanical microenvironment in case of PNI. These tissue engineering nerve grafts display optimized mechanical properties and outstanding mechanomodulatory effects, but a few bottlenecks restrict their application scenes. In this review, the current understanding in biomechanical microenvironment homeostasis associated with peripheral nerve function and PNR is integrated, where we proposed the importance of balances of mechanosensitive elements, cytoskeletal structures, mechanotransduction cascades, and extracellular matrix components; a wide variety of promising tissue engineering strategies based on biomechanical modulation are introduced with some suggestions and prospects for future directions.
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Affiliation(s)
- Lingchi Kong
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.,Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 200233, China.,Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Xin Gao
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Belt and Road Joint Laboratory of Advanced Fiber and Low-dimension Materials, College of Materials Science and Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai, 201620, China
| | - Yun Qian
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.,Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 200233, China.,Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.,✉ Corresponding authors: Yun Qian, E-mail: ; Wei Sun, E-mail: ; Zhengwei You, E-mail: ; Cunyi Fan, E-mail:
| | - Wei Sun
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Belt and Road Joint Laboratory of Advanced Fiber and Low-dimension Materials, College of Materials Science and Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai, 201620, China.,✉ Corresponding authors: Yun Qian, E-mail: ; Wei Sun, E-mail: ; Zhengwei You, E-mail: ; Cunyi Fan, E-mail:
| | - Zhengwei You
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Belt and Road Joint Laboratory of Advanced Fiber and Low-dimension Materials, College of Materials Science and Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai, 201620, China.,✉ Corresponding authors: Yun Qian, E-mail: ; Wei Sun, E-mail: ; Zhengwei You, E-mail: ; Cunyi Fan, E-mail:
| | - Cunyi Fan
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.,Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 200233, China.,Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.,✉ Corresponding authors: Yun Qian, E-mail: ; Wei Sun, E-mail: ; Zhengwei You, E-mail: ; Cunyi Fan, E-mail:
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14
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Singh VK, Haq A, Tiwari M, Saxena AK. Approach to management of nerve gaps in peripheral nerve injuries. Injury 2022; 53:1308-1318. [PMID: 35105440 DOI: 10.1016/j.injury.2022.01.031] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 01/17/2022] [Accepted: 01/17/2022] [Indexed: 02/02/2023]
Abstract
Peripheral nerve injuries (PNI) are a major clinical problem. In general, PNI results from motor vehicle accidents, lacerations with sharp objects, penetrating trauma (gunshot wounds) and stretching or crushing trauma and fractures. They can result in significant morbidity, including motor and/or sensory loss, which can affect significantly the life of the patient. Currently, the standard surgical technique for complete nerve transection is end-to-end neurorrhaphy. Unfortunately, there is segmental loss of the nerve trunk in some cases where nerve mobilization may permit end-to-end neurorrhaphy if the gap is less than 1 cm. When the nerve gap exceeds 1 cm, autologous nerve grafting is the gold standard of treatment. But in light of limited availability and concerned donor site morbidity, other techniques have been used: vascularized nerve grafts, cellular and acellular allografts, nerve conduits, nerve transfers and end-to-side neurorrhaphy. This review intends to present an overview of the literature on the applications of these techniques in repair of peripheral nerve injuries. This article also focuses on preoperative assessment, surgical timing, available options and future perspectives.
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Affiliation(s)
- Veena K Singh
- Department of Burns & Plastic surgery, All India Institute of Medical Sciences, Patna, Bihar, India.
| | - Ansarul Haq
- Department of Burns & Plastic surgery, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Meenakshi Tiwari
- Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Ajit K Saxena
- Department of Pathology/Lab Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
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15
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Bianchi S, Mauler F. Ultrasound Appearance of In Vitro Nerve Allografts and Conduits for Peripheral Nerve Reconstruction. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2022; 41:763-771. [PMID: 34037265 DOI: 10.1002/jum.15757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 05/04/2021] [Accepted: 05/09/2021] [Indexed: 06/12/2023]
Abstract
Ultrasound enables the accurate assessment of traumatic disorders of small peripheral nerves of extremities. Human nerve allografts and nerve conduits are increasingly used for the surgical treatment of nerve trauma but ultrasound reports on this field are scarce in the radiological literature. We present the macroscopic and in vitro ultrasound appearance of human allografts, and synthetic and biological conduits. In addition, we describe the ultrasound findings in some patients operated upon using the same devices. The in vitro ultrasound appearance correlated well with the macroscopic appearance of the devices. Awareness of their appearance in vitro can help sonologists when examining postsurgical patients.
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Affiliation(s)
| | - Flavien Mauler
- Division of Plastic Surgery and Hand Surgery, Kantonsspital Aarau, Aarau, Switzerland
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16
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Wolfe EM, Mathis SA, Ovadia SA, Panthaki ZJ. Comparison of Collagen and Human Amniotic Membrane Nerve Wraps and Conduits for Peripheral Nerve Repair in Preclinical Models: A Systematic Review of the Literature. J Reconstr Microsurg 2022; 39:245-253. [PMID: 35008116 DOI: 10.1055/s-0041-1732432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Collagen and human amniotic membrane (hAM) are Food and Drug Administration (FDA)-approved biomaterials that can be used as nerve wraps or conduits for repair of peripheral nerve injuries. Both biomaterials have been shown to reduce scarring and fibrosis of injured peripheral nerves. However, comparative advantages and disadvantages have not been definitively shown in the literature. The purpose of this systematic review is to comprehensively evaluate the literature regarding the roles of hAM and collagen nerve wraps and conduits on peripheral nerve regeneration in preclinical models. METHODS The MEDLINE database was queried using the PubMed search engine on July 7, 2019, with the following search strategy: ("amniotic membrane" OR "amnion") OR ("collagen conduit" OR "nerve wrap")] AND "nerve." All resulting articles were screened by two independent reviewers. Nerve type, lesion type/injury model, repair type, treatment, and outcomes were assessed. RESULTS Two hundred and fifty-eight articles were identified, and 44 studies remained after application of inclusion and exclusion criteria. Seventeen studies utilized hAM, whereas 27 studies utilized collagen wraps or conduits. Twenty-three (85%) of the collagen studies utilized conduits, and four (15%) utilized wraps. Six (35%) of the hAM studies utilized conduits and 11 (65%) utilized wraps. Two (9%) collagen studies involving a conduit and one (25%) involving a wrap demonstrated at least one significant improvement in outcomes compared with a control. While none of the hAM conduit studies showed significant improvements, eight (73%) of the studies investigating hAM wraps showed at least one significant improvement in outcomes. CONCLUSION The majority of studies reported positive outcomes, indicating that collagen and hAM nerve wraps and conduits both have the potential to enhance peripheral nerve regeneration. However, relatively few studies reported significant findings, except for studies evaluating hAM wraps. Preclinical models may help guide clinical practice regarding applications of these biomaterials in peripheral nerve repair.
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Affiliation(s)
- Erin M Wolfe
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
| | - Sydney A Mathis
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
| | - Steven A Ovadia
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
| | - Zubin J Panthaki
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
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17
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Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote the Proliferation of Schwann Cells by Regulating the PI3K/AKT Signaling Pathway via Transferring miR-21. Stem Cells Int 2021; 2021:1496101. [PMID: 34552631 PMCID: PMC8452411 DOI: 10.1155/2021/1496101] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/07/2021] [Indexed: 12/13/2022] Open
Abstract
As an alternative mesenchymal stem cell- (MSC-) based therapy, MSC-derived extracellular vesicles (EVs) have shown promise in the field of regenerative medicine. We previously found that human umbilical cord mesenchymal stem cell-derived EVs (hUCMSC-EVs) improved functional recovery and nerve regeneration in a rat model of sciatic nerve transection. However, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that hUCMSC-EVs promoted the proliferation of Schwann cells by activating the PI3K/AKT signaling pathway. Furthermore, we showed that hUCMSC-EVs mediated Schwann cell proliferation via transfer of miR-21. Our findings highlight a novel mechanism of hUCMSC-EVs in treating peripheral nerve injury and suggest that hUCMSC-EVs may be an attractive option for clinical application in the treatment of peripheral nerve injury.
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18
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Peripheral Nerve Regeneration Using Different Germ Layer-Derived Adult Stem Cells in the Past Decade. Behav Neurol 2021; 2021:5586523. [PMID: 34539934 PMCID: PMC8448597 DOI: 10.1155/2021/5586523] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 07/27/2021] [Accepted: 08/09/2021] [Indexed: 12/15/2022] Open
Abstract
Peripheral nerve injuries (PNIs) are some of the most common types of traumatic lesions affecting the nervous system. Although the peripheral nervous system has a higher regenerative ability than the central nervous system, delayed treatment is associated with disturbances in both distal sensory and functional abilities. Over the past decades, adult stem cell-based therapies for peripheral nerve injuries have drawn attention from researchers. This is because various stem cells can promote regeneration after peripheral nerve injuries by differentiating into neural-line cells, secreting various neurotrophic factors, and regulating the activity of in situ Schwann cells (SCs). This article reviewed research from the past 10 years on the role of stem cells in the repair of PNIs. We concluded that adult stem cell-based therapies promote the regeneration of PNI in various ways.
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19
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Ahmed MN, Shi D, Dailey MT, Rothermund K, Drewry MD, Calabrese TC, Cui XT, Syed-Picard FN. Dental Pulp Cell Sheets Enhance Facial Nerve Regeneration via Local Neurotrophic Factor Delivery. Tissue Eng Part A 2021; 27:1128-1139. [PMID: 33164704 PMCID: PMC8616747 DOI: 10.1089/ten.tea.2020.0265] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
An effective strategy for sustained neurotrophic factor (NTF) delivery to sites of peripheral nerve injury (PNI) would accelerate healing and enhance functional recovery, addressing the major clinical challenges associated with the current standard of care. In this study, scaffold-free cell sheets were generated using human dental pulp stem/progenitor cells, that endogenously express high levels of NTFs, for use as bioactive NTF delivery systems. Additionally, the effect of fibroblast growth factor 2 (FGF2) on NTF expression by dental pulp cell (DPC) sheets was evaluated. In vitro analysis confirmed that DPC sheets express high levels of NTF messenger RNA (mRNA) and proteins, and the addition of FGF2 to DPC sheet culture increased total NTF production by significantly increasing the cellularity of sheets. Furthermore, the DPC sheet secretome stimulated neurite formation and extension in cultured neuronal cells, and these functional effects were further enhanced when DPC sheets were cultured with FGF2. These neuritogenic results were reversed by NTF inhibition substantiating that DPC sheets have a positive effect on neuronal cell activity through the production of NTFs. Further evaluation of DPC sheets in a rat facial nerve crush injury model in vivo established that in comparison with untreated controls, nerves treated with DPC sheets had greater axon regeneration through the injury site and superior functional recovery as quantitatively assessed by compound muscle action potential measurements. This study demonstrates the use of DPC sheets as vehicles for NTF delivery that could augment the current methods for treating PNIs to accelerate regeneration and enhance the functional outcome. Impact statement The major challenges associated with current treatments of peripheral nerve injuries (PNIs) are prolonged repair times and insufficient functional recovery. Dental pulp stem/progenitor cells (DPCs) are known to endogenously express high levels of neurotrophic factors (NTFs), growth factors that enhance axon regeneration. In this study, we demonstrate that scaffold-free DPC sheets can act as effective carrier systems to facilitate the delivery and retention of NTF-producing DPCs to sites of PNIs and improve functional nerve regeneration. DPC sheets have high translational feasibility and could augment the current standard of care to enhance the quality of life for patients dealing with PNIs.
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Affiliation(s)
- Meer N. Ahmed
- Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Delin Shi
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Matthew T. Dailey
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kristi Rothermund
- Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Michelle D. Drewry
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Tia C. Calabrese
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Xinyan T. Cui
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Fatima N. Syed-Picard
- Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania USA
- Address correspondence to: Fatima N. Syed-Picard, MSE, PhD, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, 413 Salk Pavilion, 355 Sutherland Drive, Pittsburgh, PA 15213, USA
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20
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Wu F, Jiao C, Yang Y, Liu F, Sun Z. Nerve conduit based on HAP/PDLLA/PRGD for peripheral nerve regeneration with sustained release of valproic acid. Cell Biol Int 2021; 45:1733-1742. [PMID: 33851759 DOI: 10.1002/cbin.11613] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 04/03/2021] [Accepted: 04/12/2021] [Indexed: 11/06/2022]
Abstract
The nerve conduits have been developed for nerve defect repair. However, no artificial conduits have obtained comparable results to autografts to bridge the large gaps. A possible reason for this poor performance may be a lack of sustainable neurotrophic support for axonal regrowth. Previous studies suggested nanocomposite conduits can be used as a carrier for valproic acid (VPA), a common drug that can produce effects similar to the neurotrophic factors. Here, we developed the novel bioabsorbable conduits based on hydroxyapatite/poly d-l-lactic acid (PDLLA)/poly{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]} with sustained release of VPA. Firstly, the sustained release of VPA in this conduit was examined by high-performance liquid chromatography. Then Schwann cells were treated with the conduit extracts. The cell metabolic activity and proliferation were assayed by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide and bromodeoxyuridine staining. A 10-mm segment of rat sciatic nerve was resected and then repaired, respectively, using the VPA conduit (Group A), the PDLLA conduit (Group B), or the autografts (Group C). Nerve conduction velocities (NCVs), compound muscle action potentials (CMAPs), and histological staining were assayed following the surgery. The cell metabolic activity and proliferation were significantly increased (p < .05) by the extracts from VPA-conduit extract compared to others. NCVs and CMAPs were significantly higher in Groups A and C than Group B (p < .05). The nerve density of Groups A and C was higher than Group B. There was no significant difference between Groups A and C. Taken together, this study suggested the sustained-release VPA conduit promoted peripheral nerve regeneration that was comparable to the autografts. It holds potential for future use in nerve regeneration.
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Affiliation(s)
- Fei Wu
- Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan, Hubei, China
| | - Chuanjie Jiao
- Department of Orthopedics, Yangxin People's Hospital, Huangshi, Hubei, China
| | - Yue Yang
- Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan, Hubei, China
| | - Feng Liu
- Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan, Hubei, China
| | - Zhibo Sun
- Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan, Hubei, China
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21
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Li C, Liu SY, Pi W, Zhang PX. Cortical plasticity and nerve regeneration after peripheral nerve injury. Neural Regen Res 2021; 16:1518-1523. [PMID: 33433465 PMCID: PMC8323687 DOI: 10.4103/1673-5374.303008] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.
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Affiliation(s)
- Ci Li
- Department of Orthopedics and Trauma, Peking University People's Hospital; Key Laboratory of Trauma and Neural Regeneration, Peking University, Beijing, China
| | - Song-Yang Liu
- Department of Orthopedics and Trauma, Peking University People's Hospital; Key Laboratory of Trauma and Neural Regeneration, Peking University, Beijing, China
| | - Wei Pi
- Department of Orthopedics and Trauma, Peking University People's Hospital; Key Laboratory of Trauma and Neural Regeneration, Peking University, Beijing, China
| | - Pei-Xun Zhang
- Department of Orthopedics and Trauma, Peking University People's Hospital; Key Laboratory of Trauma and Neural Regeneration, Peking University; National Center for Trauma Medicine, Beijing, China
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22
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Millán D, Jiménez RA, Nieto LE, Poveda IY, Torres MA, Silva AS, Ospina LF, Mano JF, Fontanilla MR. Adjustable conduits for guided peripheral nerve regeneration prepared from bi-zonal unidirectional and multidirectional laminar scaffold of type I collagen. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 121:111838. [PMID: 33579476 DOI: 10.1016/j.msec.2020.111838] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 12/14/2020] [Accepted: 12/22/2020] [Indexed: 11/24/2022]
Abstract
Shortness of donor nerves has led to the development of nerve conduits that connect sectioned peripheral nerve stumps and help to prevent the formation of neuromas. Often, the standard diameters of these devices cannot be adapted at the time of surgery to the diameter of the nerve injured. In this work, scaffolds were developed to form filled nerve conduits with an inner matrix with unidirectional channels covered by a multidirectional pore zone. Collagen type I dispersions (5 mg/g and 8 mg/g) were sequentially frozen using different methods to obtain six laminar scaffolds (P1 to P5) formed by a unidirectional (U) pore/channel zone adjacent to a multidirectional (M) pore zone. The physicochemical and microstructural properties of the scaffolds were determined and compared, as well as their biodegradability, residual glutaraldehyde and cytocompatibility. Also, the Young's modulus of the conduits made by rolling up the bizonal scaffolds from the unidirectional to the multidirectional zone was determined. Based on these comparisons, the proliferation and differentiation of hASC were assessed only in the P3 scaffolds. The cells adhered, aligned in the same direction as the unidirectional porous fibers, proliferated, and differentiated into Schwann-like cells. Adjustable conduits made with the P3 scaffold were implanted in rats 10 mm sciatic nerve lesions to compare their performance with that of autologous sciatic nerve grafted lesions. The in vivo results demonstrated that the tested conduit can be adapted to the diameter of the nerve stumps to guide their growth and promote their regeneration.
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Affiliation(s)
- Diana Millán
- Tissue Engineering Group, Department of Pharmacy, Universidad Nacional de Colombia, Av. Carrera 30 # 45-10, 111321 Bogotá, Colombia; Universidad El Bosque, Facultad de Medicina, Colombia.
| | - Ronald A Jiménez
- Tissue Engineering Group, Department of Pharmacy, Universidad Nacional de Colombia, Av. Carrera 30 # 45-10, 111321 Bogotá, Colombia; Universidad El Bosque, Facultad de Ciencias, Colombia.
| | - Luis E Nieto
- Facultad de Medicina, Pontificia Universidad Javeriana, Carrera 7 # 40-62 Of 726, Bogotá, Colombia.
| | - Ivan Y Poveda
- Tissue Engineering Group, Department of Pharmacy, Universidad Nacional de Colombia, Av. Carrera 30 # 45-10, 111321 Bogotá, Colombia.
| | - Maria A Torres
- Tissue Engineering Group, Department of Pharmacy, Universidad Nacional de Colombia, Av. Carrera 30 # 45-10, 111321 Bogotá, Colombia.
| | - Ana S Silva
- Department of Chemistry, CICECO, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Luis F Ospina
- Department of Pharmacy, Universidad Nacional de Colombia, 111321, Av. Carrera 30 # 45-10, Bogotá, Colombia.
| | - João F Mano
- Department of Chemistry, CICECO, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Marta R Fontanilla
- Tissue Engineering Group, Department of Pharmacy, Universidad Nacional de Colombia, Av. Carrera 30 # 45-10, 111321 Bogotá, Colombia.
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23
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Smith TA, Ghergherehchi CL, Mikesh M, Shores JT, Tucker HO, Bittner GD. Polyethylene glycol-fusion repair of sciatic allografts in female rats achieves immunotolerance via attenuated innate and adaptive responses. J Neurosci Res 2020; 98:2468-2495. [PMID: 32931034 DOI: 10.1002/jnr.24720] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 07/31/2020] [Accepted: 08/11/2020] [Indexed: 12/17/2022]
Abstract
Ablation/segmental loss peripheral nerve injuries (PNIs) exhibit poor functional recovery due to slow and inaccurate outgrowth of regenerating axons. Viable peripheral nerve allografts (PNAs) as growth-guide conduits are immunologically rejected and all anucleated donor/host axonal segments undergo Wallerian degeneration. In contrast, we report that ablation-type sciatic PNIs repaired by neurorrhaphy of viable sciatic PNAs and a polyethylene glycol (PEG)-fusion protocol using PEG immediately restored axonal continuity for many axons, reinnervated/maintained their neuromuscular junctions, and prevented much Wallerian degeneration. PEG-fused PNAs permanently restored many sciatic-mediated behaviors within 2-6 weeks. PEG-fused PNAs were not rejected even though host/donors were neither immunosuppressed nor tissue-matched in outbred female Sprague Dawley rats. Innate and adaptive immune responses to PEG-fused sciatic PNAs were analyzed using electron microscopy, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction for morphological features, T cell and macrophage infiltration, major histocompatibility complex (MHC) expression, apoptosis, expression of cytokines, chemokines, and cytotoxic effectors. PEG-fused PNAs exhibited attenuated innate and adaptive immune responses by 14-21 days postoperatively, as evidenced by (a) many axons and cells remaining viable, (b) significantly reduced infiltration of cytotoxic and total T cells and macrophages, (c) significantly reduced expression of inflammatory cytokines, chemokines, and MHC proteins, (d) consistently low apoptotic response. Morphologically and/or biochemically, PEG-fused sciatic PNAs often resembled sciatic autografts or intact sciatic nerves. In brief, PEG-fused PNAs are an unstudied, perhaps unique, example of immune tolerance of viable allograft tissue in a nonimmune-privileged environment and could greatly improve the clinical outcomes for PNIs relative to current protocols.
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Affiliation(s)
- Tyler A Smith
- Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA
| | | | - Michelle Mikesh
- Department of Neuroscience, University of Texas at Austin, Austin, TX, USA
| | - Jaimie T Shores
- Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Haley O Tucker
- Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA
| | - George D Bittner
- Department of Neuroscience, University of Texas at Austin, Austin, TX, USA
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Smith TA, Ghergherehchi CL, Tucker HO, Bittner GD. Coding transcriptome analyses reveal altered functions underlying immunotolerance of PEG-fused rat sciatic nerve allografts. J Neuroinflammation 2020; 17:287. [PMID: 33008419 PMCID: PMC7532577 DOI: 10.1186/s12974-020-01953-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 09/16/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Current methods to repair ablation-type peripheral nerve injuries (PNIs) using peripheral nerve allografts (PNAs) often result in poor functional recovery due to immunological rejection as well as to slow and inaccurate outgrowth of regenerating axonal sprouts. In contrast, ablation-type PNIs repaired by PNAs, using a multistep protocol in which one step employs the membrane fusogen polyethylene glycol (PEG), permanently restore sciatic-mediated behaviors within weeks. Axons and cells within PEG-fused PNAs remain viable, even though outbred host and donor tissues are neither immunosuppressed nor tissue matched. PEG-fused PNAs exhibit significantly reduced T cell and macrophage infiltration, expression of major histocompatibility complex I/II and consistently low apoptosis. In this study, we analyzed the coding transcriptome of PEG-fused PNAs to examine possible mechanisms underlying immunosuppression. METHODS Ablation-type sciatic PNIs in adult Sprague-Dawley rats were repaired using PNAs and a PEG-fusion protocol combined with neurorrhaphy. Electrophysiological and behavioral tests confirmed successful PEG-fusion of PNAs. RNA sequencing analyzed differential expression profiles of protein-coding genes between PEG-fused PNAs and negative control PNAs (not treated with PEG) at 14 days PO, along with unoperated control nerves. Sequencing results were validated by quantitative reverse transcription PCR (RT-qPCR), and in some cases, immunohistochemistry. RESULTS PEG-fused PNAs display significant downregulation of many gene transcripts associated with innate and adaptive allorejection responses. Schwann cell-associated transcripts are often upregulated, and cellular processes such as extracellular matrix remodeling and cell/tissue development are particularly enriched. Transcripts encoding several potentially immunosuppressive proteins (e.g., thrombospondins 1 and 2) also are upregulated in PEG-fused PNAs. CONCLUSIONS This study is the first to characterize the coding transcriptome of PEG-fused PNAs and to identify possible links between alterations of the extracellular matrix and suppression of the allorejection response. The results establish an initial molecular basis to understand mechanisms underlying PEG-mediated immunosuppression.
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Affiliation(s)
- Tyler A Smith
- Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA
| | | | - Haley O Tucker
- Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA
| | - George D Bittner
- Department of Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA.
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25
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Stewart CE, Kan CFK, Stewart BR, Sanicola HW, Jung JP, Sulaiman OAR, Wang D. Machine intelligence for nerve conduit design and production. J Biol Eng 2020; 14:25. [PMID: 32944070 PMCID: PMC7487837 DOI: 10.1186/s13036-020-00245-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 08/13/2020] [Indexed: 02/08/2023] Open
Abstract
Nerve guidance conduits (NGCs) have emerged from recent advances within tissue engineering as a promising alternative to autografts for peripheral nerve repair. NGCs are tubular structures with engineered biomaterials, which guide axonal regeneration from the injured proximal nerve to the distal stump. NGC design can synergistically combine multiple properties to enhance proliferation of stem and neuronal cells, improve nerve migration, attenuate inflammation and reduce scar tissue formation. The aim of most laboratories fabricating NGCs is the development of an automated process that incorporates patient-specific features and complex tissue blueprints (e.g. neurovascular conduit) that serve as the basis for more complicated muscular and skin grafts. One of the major limitations for tissue engineering is lack of guidance for generating tissue blueprints and the absence of streamlined manufacturing processes. With the rapid expansion of machine intelligence, high dimensional image analysis, and computational scaffold design, optimized tissue templates for 3D bioprinting (3DBP) are feasible. In this review, we examine the translational challenges to peripheral nerve regeneration and where machine intelligence can innovate bottlenecks in neural tissue engineering.
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Affiliation(s)
- Caleb E. Stewart
- Current Affiliation: Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport Louisiana, USA
| | - Chin Fung Kelvin Kan
- Current Affiliation: Department of General Surgery, Brigham and Women’s Hospital, Boston, MA 02115 USA
| | - Brody R. Stewart
- Current Affiliation: Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905 USA
| | - Henry W. Sanicola
- Current Affiliation: Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport Louisiana, USA
| | - Jangwook P. Jung
- Department of Biological Engineering, Louisiana State University, Baton Rouge, LA 70803 USA
| | - Olawale A. R. Sulaiman
- Ochsner Neural Injury & Regeneration Laboratory, Ochsner Clinic Foundation, New Orleans, LA 70121 USA
- Department of Neurosurgery, Ochsner Clinic Foundation, New Orleans, 70121 USA
| | - Dadong Wang
- Quantitative Imaging Research Team, Data 61, Commonwealth Scientific and Industrial Research Organization, Marsfield, NSW 2122 Australia
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The Potential of Acellular Dermal Matrix Combined With Neural Stem Cells Induced From Human Adipose-Derived Stem Cells in Nerve Tissue Engineering. Ann Plast Surg 2020; 82:S108-S118. [PMID: 30540605 DOI: 10.1097/sap.0000000000001731] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Reconstruction of segmental peripheral nerve gap is still challenging when the autografts are unavailable owing to limited availability of donor site and functional recovery. The creation of artificial conduits composed of biological or synthetic materials is still developing. Acellular dermal matrix (ADM) has been widely studied and its extension and plasticity properties may become suitable nerve conduits under different forms of nerve gaps. Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell types of different germ layers including neural stem cells (NSCs). The purpose of this experiment is to use ADM as a scaffold combined with NSCs induced by ADSCs to establish neural tissue engineering. METHODS The ADSCs were isolated from syringe-liposuction adipose tissue harvested from abdominal fat and then cultured in keratinocyte serum free media to trigger into neural stem cells. Stem cells were confirmed by the expression of surface markers nestin and SOX2 in NSCs with Western blot and immunofluorescent staining. Matrix enzyme treatment was used to obtain ADM to remove immunogenic cells while maintaining the integrity of the basement membrane complex and the extracellular matrix structure of the dermis. The NSCs were cocultured with ADM for 3 days, and survival markers Ki67 and neural stem cell markers nestin were detected. RESULTS These NSCs can form neurospheres and express nestin and SOX2. The NSC can further coculture with ADM, and it will continue to express survivor markers and neural stem cell markers on ADM. CONCLUSIONS These findings provide evidence that the combination of ADM and NSC has the same potential as neural tissue engineering as other acellular sciatic nerve.
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Wei S, Hu Q, Cheng X, Ma J, Liang X, Peng J, Xu W, Sun X, Han G, Ma X, Wang Y. Differences in the Structure and Protein Expression of Femoral Nerve Branches in Rats. Front Neuroanat 2020; 14:16. [PMID: 32322192 PMCID: PMC7156789 DOI: 10.3389/fnana.2020.00016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 03/18/2020] [Indexed: 11/13/2022] Open
Affiliation(s)
- Shuai Wei
- Tianjin Hospital Tianjin University, Tianjin, China
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Qian Hu
- Department of Geriatrics, The Second People’s Hospital of Nantong, Nantong, China
| | - Xiaoqing Cheng
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Jianxiong Ma
- Tianjin Hospital Tianjin University, Tianjin, China
| | - Xuezhen Liang
- The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Shandong, China
| | - Jiang Peng
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Wenjing Xu
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Xun Sun
- Tianjin Hospital Tianjin University, Tianjin, China
| | - Gonghai Han
- The First People’s Hospital of Yunnan Province, Kunming, China
| | - Xinlong Ma
- Tianjin Hospital Tianjin University, Tianjin, China
- *Correspondence: Xinlong Ma Yu Wang
| | - Yu Wang
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
- *Correspondence: Xinlong Ma Yu Wang
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28
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Bagher Z, Ehterami A, Nasrolahi M, Azimi M, Salehi M. Hesperidin promotes peripheral nerve regeneration based on tissue engineering strategy using alginate/chitosan hydrogel: in vitro and in vivo study. INT J POLYM MATER PO 2020. [DOI: 10.1080/00914037.2020.1713781] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Zohreh Bagher
- ENT and Head & Neck Research Center and Department, the Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Arian Ehterami
- Department of Mechanical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mohammad Nasrolahi
- Faculty of Tissue Engineering, Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Maryam Azimi
- Immunology Research Center, Institute of Immunology and Infection Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Majid Salehi
- Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
- Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
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Li T, Sui Z, Matsuno A, Ten H, Oyama K, Ito A, Jiang H, Ren X, Javed R, Zhang L, Ao Q. Fabrication and Evaluation of a Xenogeneic Decellularized Nerve-Derived Material: Preclinical Studies of a New Strategy for Nerve Repair. Neurotherapeutics 2020; 17:356-370. [PMID: 31758411 PMCID: PMC7007487 DOI: 10.1007/s13311-019-00794-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The repair and regeneration of transected peripheral nerves is an important area of clinical research, and the adhesion of anastomosis sites to surrounding tissues is a vital factor affecting the quality of nerve recovery after nerve anastomosis. This study involves the generation of a novel nerve repair membrane derived from decellularized porcine nerves using a unique, innovative technique. The decellularized nerve matrix was verified to be effective in eliminating cellular components, and it still retained some neural extracellular matrix components and bioactive molecules (collagens, glycosaminoglycans, laminin, fibronectin, TGF-β, etc.), which were mainly determined by proteomic analysis, histochemistry, immunohistochemistry, and enzyme-linked immunosorbent assay. Cytotoxicity, intracutaneous reactivity, hemolysis, and cell affinity analyses were conducted to confirm the biosecurity of the nerve repair membrane. The in vivo functionality was assessed in a rat sciatic nerve transection model, and indices of functional nerve recovery, including the measurement of the claw-spread reflex, nerve anastomosis site adhesion, electrophysiological properties, and the number of regenerated nerve fibers, were evaluated. The results indicated that the nerve repair membrane could effectively prevent adhesion between the nerve anastomosis sites and the surrounding tissues and enhance nerve regeneration, which could be attributed to its various bioactive components. In conclusion, the novel nerve repair membrane derived from xenogeneic decellularized nerves described in this study shows great potential auxiliary clinical treatment for peripheral nerve injuries.
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Affiliation(s)
- Ting Li
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Zhigang Sui
- Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
| | - Akira Matsuno
- Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Hirotomo Ten
- Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan
- Department of Judo Physical Therapy, Faculty of Health, Teikyo Heisei University, Tokyo, Japan
| | - Kenichi Oyama
- Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Akihiro Ito
- Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Hong Jiang
- Shandong Junxiu Biotechnology Company, Limited, Yantai, China
| | - Xiaomin Ren
- Shandong Junxiu Biotechnology Company, Limited, Yantai, China
| | - Rabia Javed
- Department of Tissue Engineering, China Medical University, Shenyang, China
| | - Lihua Zhang
- Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
| | - Qiang Ao
- Department of Tissue Engineering, China Medical University, Shenyang, China.
- Institute of Regulatory Science for Medical Devices, Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China.
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30
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De Masi A, Tonazzini I, Masciullo C, Mezzena R, Chiellini F, Puppi D, Cecchini M. Chitosan films for regenerative medicine: fabrication methods and mechanical characterization of nanostructured chitosan films. Biophys Rev 2019; 11:807-815. [PMID: 31529358 PMCID: PMC6815298 DOI: 10.1007/s12551-019-00591-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 09/02/2019] [Indexed: 12/17/2022] Open
Abstract
Regenerative medicine is continuously facing new challenges and it is searching for new biocompatible, green/natural polymer materials, possibly biodegradable and non-immunogenic. Moreover, the critical importance of the nano/microstructuring of surfaces is overall accepted for their full biocompatibility and in vitro/in vivo performances. Chitosan is emerging as a promising biopolymer for tissue engineering and its application can be further improved by exploiting its nano/microstructuration. Here, we report the state of the art of chitosan films and scaffolds nano/micro-structuration. We show that it is possible to obtain, by solvent casting, chitosan thin films with good mechanical properties and to structure them at the microscale and even nanoscale level, with resolutions down to 100 nm.
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Affiliation(s)
- Alessia De Masi
- NEST, Scuola Normale Superiore, Piazza San Silvestro 12, 56127, Pisa, Italy
| | - Ilaria Tonazzini
- NEST, Istituto Nanoscienze-CNR, Piazza San Silvestro 12, 56127, Pisa, Italy.
| | - Cecilia Masciullo
- NEST, Scuola Normale Superiore, Piazza San Silvestro 12, 56127, Pisa, Italy
| | - Roberta Mezzena
- NEST, Scuola Normale Superiore, Piazza San Silvestro 12, 56127, Pisa, Italy
| | - Federica Chiellini
- Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM PISA, Via G. Moruzzi 13, 56124, Pisa, Italy
| | - Dario Puppi
- Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM PISA, Via G. Moruzzi 13, 56124, Pisa, Italy
| | - Marco Cecchini
- NEST, Scuola Normale Superiore, Piazza San Silvestro 12, 56127, Pisa, Italy
- NEST, Istituto Nanoscienze-CNR, Piazza San Silvestro 12, 56127, Pisa, Italy
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31
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Syu WZ, Hueng DY, Chen WL, Chan JYH, Chen SG, Huang SM. Adipose-Derived Neural Stem Cells Combined with Acellular Dermal Matrix as a Neural Conduit Enhances Peripheral Nerve Repair. Cell Transplant 2019; 28:1220-1230. [PMID: 31148461 PMCID: PMC6767887 DOI: 10.1177/0963689719853512] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Reconstruction to close a peripheral nerve gap continues to be a challenge for clinical
medicine, and much effort is being made to develop nerve conduits facilitate nerve gap
closure. Acellular dermal matrix (ADM) is mainly used to aid wound healing, but its
malleability and plasticity potentially enable it to be used in the treatment of nerve
gaps. Adipose-derived stem cells (ADSCs) can be differentiated into three germ layer
cells, including neurospheres. We tested the ability of ADSC-derived neural stem cells
(NSCs) in combination with ADM or acellular sciatic nerve (ASN) to repair a transected
sciatic nerve. We found that NSCs form neurospheres that express Nestin and Sox2, and
could be co-cultured with ADM in vitro, where they express the survival marker Ki67.
Following sciatic nerve transection in rats, treatment with ADM+NSC or ASN+NSC led to
increases in relative gastrocnemius weight, cross-sectional muscle fiber area, and sciatic
functional index as compared with untreated rats or rats treated with ADM or ASN alone.
These findings suggest that ADM combined with NSCs can improve peripheral nerve gap repair
after nerve transection and may also be useful for treating other types of neurological
gaps.
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Affiliation(s)
- Wei-Ze Syu
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei
| | - Dueng-Yuan Hueng
- Department of Biochemistry, National Defense Medical Center, Taipei.,Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Wei-Liang Chen
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, and School of Medicine, National Defense Medical Center, Taipei
| | - James Yi-Hsin Chan
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei.,Superintendent's Office, National Defense Medical Center, Taipei
| | - Shyi-Gen Chen
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei.,Division of Plastic and Reconstructive Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Shih-Ming Huang
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei.,Department of Biochemistry, National Defense Medical Center, Taipei
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32
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Bassilios Habre S, Bond G, Jing XL, Kostopoulos E, Wallace RD, Konofaos P. The Surgical Management of Nerve Gaps: Present and Future. Ann Plast Surg 2019; 80:252-261. [PMID: 29166306 DOI: 10.1097/sap.0000000000001252] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Peripheral nerve injuries can result in significant morbidity, including motor and/or sensory loss, which can affect significantly the life of the patient. Nowadays, the gold standard for the treatment of nerve section is end-to-end neurorrhaphy. Unfortunately, in some cases, there is segmental loss of the nerve trunk. Nerve mobilization allows primary repair of the sectioned nerve by end-to-end neurorrhaphy if the gap is less than 1 cm. When the nerve gap exceeds 1 cm, autologous nerve grafting is the gold standard of treatment. To overcome the limited availability and the donor site morbidity, other techniques have been used: vascularized nerve grafts, cellular and acellular allografts, nerve conduits, nerve transfers, and end-to-side neurorrhaphy. The purpose of this review is to present an overview of the literature on the applications of these techniques in peripheral nerve repair. Furthermore, preoperative evaluation, timing of repair, and future perspectives are also discussed.
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33
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Jia Y, Yang W, Zhang K, Qiu S, Xu J, Wang C, Chai Y. Nanofiber arrangement regulates peripheral nerve regeneration through differential modulation of macrophage phenotypes. Acta Biomater 2019; 83:291-301. [PMID: 30541701 DOI: 10.1016/j.actbio.2018.10.040] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 10/09/2018] [Accepted: 10/25/2018] [Indexed: 12/20/2022]
Abstract
Topographical cues presented by aligned nanofibers have been demonstrated to stimulate peripheral nerve regeneration across long gaps, but the underlying mechanisms remain incompletely elucidated. Because macrophages play a crucial role in peripheral nerve regeneration and can be phenotypically modulated by topographical cues, we hypothesized that aligned nanofibers might induce the development of macrophage phenotypes that facilitate the regeneration of peripheral nerves. Here, macrophages were seeded on aligned and random poly(l-lactic acid-co-ε-caprolactone) nanofibers and their morphology and phenotypes were compared. Aligned nanofibers drastically stimulated macrophage elongation along the nanofibers, and, more importantly, induced the development of a pro-healing macrophage phenotype (M2 type), whereas random nanofibers induced a proinflammatory phenotype (M1 type). Notably, the macrophages polarized by aligned nanofibers potently promoted the proliferation and migration of Schwann cells in vitro. Thus, we constructed nerve-guidance conduits by using aligned and random nanofibers and evaluated their effects on macrophage polarization and nerve regeneration in a rat sciatic nerve defect model. Our in vivo results showed that the ratio of pro-healing macrophages was again higher in the aligned-nanofiber group, and further that Schwann cell infiltration and axon numbers were 2.0- and 2.84-fold higher in the aligned group than in the random group, respectively. This study demonstrates that nanofiber arrangement differentially regulates macrophage activation and that nerve-guidance conduits constructed from aligned nanofibers markedly facilitate peripheral nerve regeneration at least partly by promoting the pro-healing phenotype in macrophages. STATEMENT OF SIGNIFICANCE: The effect of aligned nanofibers on peripheral nerve regeneration has been well established. However, the underlying mechanism remains unclear. Since macrophages play an important role in peripheral nerve regeneration, and can be phenotypically modulated by topographical cues, we hypothesized that aligned nanofibers may exert their beneficial effects via modulating macrophage phenotypes. This study demonstrates for the first time that nanofiber arrangement differentially modulates macrophage shape and polarization, and this subsequently influences the outcome of peripheral nerve regeneration. These findings reveals a novel relationship between biomaterial structure and macrophage activation, contributes to clarifying the mechanism of surface topography in tissue regeneration, and highlight the potential application prospect of aligned nanofiber scaffolds in nerve regeneration and wound healing.
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Affiliation(s)
- Yachao Jia
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Weichao Yang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Kuihua Zhang
- College of Materials and Textile Engineering, Jiaxing University, Zhejiang 314001, China
| | - Shuo Qiu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Jia Xu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Chunyang Wang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
| | - Yimin Chai
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
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Achyranthes bidentata polypeptides promotes migration of Schwann cells via NOX4/DUOX2-dependent ROS production in rats. Neurosci Lett 2018; 696:99-107. [PMID: 30572102 DOI: 10.1016/j.neulet.2018.12.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/29/2018] [Accepted: 12/16/2018] [Indexed: 12/30/2022]
Abstract
Achyranthes bidentata polypeptides (ABPP), an active polypeptides isolated from the aqueous extract of Achyranthes bidentata Blume, contributes to the regeneration of injured peripheral nerves by promoting migration of Schwann cells (SCs). In this study, we aimed to investigate the possible mechanism underlying the ABPP-induced migration of primary cultured rat SCs. Transwell migration assays indicated that ABPP promoted SCs migration in a concentration-dependent manner by inducing production of NADPH-oxidase (NOX)-derived reactive oxygen species (ROS). Inhibition of ROS production by NOXs inhibitor apocynin (APO) or diphenyleneiodonium (DPI) partially blocked ABPP-mediated SCs migration. Furthermore, by using real-time polymerase chain reaction analysis and siRNA interference technique, we verified the participation of NOX subunit 4 (NOX4) and dual oxidase 2 (DUOX2) in ABPP-induced ROS production and consequential SCs migration. Taken together, these results demonstrated that ABPP promoted SCs migration via NOX4/DUOX2-activated ROS in SCs.
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35
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Dixon AR, Jariwala SH, Bilis Z, Loverde JR, Pasquina PF, Alvarez LM. Bridging the gap in peripheral nerve repair with 3D printed and bioprinted conduits. Biomaterials 2018; 186:44-63. [DOI: 10.1016/j.biomaterials.2018.09.010] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 09/06/2018] [Accepted: 09/07/2018] [Indexed: 01/14/2023]
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36
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Vascularized Brachial Plexus Allotransplantation-An Experimental Study in Brown Norway and Lewis Rats. Transplantation 2018; 103:149-159. [PMID: 30048401 DOI: 10.1097/tp.0000000000002387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Brachial plexus injuries are devastating. Current reconstructive treatments achieve limited partial functionality. Vascularized brachial plexus allotransplantation could offer the best nerve graft fulfilling the like-with-like principle. In this experimental study, we assessed the feasibility of rat brachial plexus allotransplantation and analyzed its functional outcomes. METHODS A free vascularized brachial plexus with a chimeric compound skin paddle flap based on the subclavian vessels was transplanted from a Brown Norway rat to a Lewis rat. This study has 2 parts. Protocol I aimed to develop the vascularized brachial plexus allotransplantation (VBP-allo) model. Four groups are compared: no reconstruction, VBP-allo with and without cyclosporine A immunosuppression, VBP autotransplantation (VBP-auto). Protocol II compared the recovery of the biceps muscle and forearm flexors when using all 5, 2 (C5 + C6) or 1 (isolated C6) spinal nerve as the donor nerves. The assessment was performed on week 16 and included muscle weight, functionality (grooming tests, muscle strength), electrophysiology and histomorphology of the targeted muscles. RESULTS Protocol I showed, the VBP-allo with cyclosporine A immunosuppression was electrophysiologically and functionally comparable to VBP-auto and significantly superior to negative controls and absent immunosuppression. In protocol II, all groups had a comparable functional recovery in the biceps muscle. Only with 5 donor nerves did the forearm show good results compared with only 1 or 2 donor nerves. CONCLUSIONS This study demonstrated a useful vascularized complete brachial plexus allotransplantation rodent model with successful forelimb function restoration under immunosuppression. Only the allotransplantation including all 5 roots as donor nerves achieved a forearm recovery.
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Gu L. [Construction of Chinese peripheral nerve society and progress in repair and reconstruction of peripheral nerve injury]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2018; 32:786-791. [PMID: 30129296 DOI: 10.7507/1002-1892.201807020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The peripheral nerve group of the reparative and reconstructive surgery committee (branch of Chinese association of rehabilitation medicine) was established in 1995. Major research progress has been made in the repair, regeneration, and reconstruction of peripheral nerve injury. Professor GU Yudong initiated the contralateral cervical7 root (CC7) transfer for the treatment of total brachial plexus root injury in 1986. Now this method has been applied safely and effectively for 30 years with profound progress and refinement. In addition, the repair and reconstruction of peripheral nerve injury had achieved great development such as the treatment of spastic paralysis of upper limb, CC7 transfer using a modified prespinal route, the reconstruction of bladder function after spinal cord injury, the development of acellular allograft nerve, the small gap suture technique, the functioning free gracilis muscle transplantation, and contralateral S 1 transfer which have been widely used in clinical application with good outcomes. With the progress of the biological manufacturing of peripheral nerve bio-materials and the remodeling of central nervous system after brachial plexus injury, a novel peripheral neuroscience research field was growing up. It is still a challenge for surgeons and scholars in this field to insist on the popularization and improvement of peripheral nerve repair and reconstruction by microsurgical technique, and to make efforts to transform the results of peripheral nerve research into clinical practice.
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Affiliation(s)
- Liqiang Gu
- Division of Orthopedic Trauma, Hand and Microsurgery, Department of Orthopedics and Microsurgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou Guangdong, 510080,
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Lin T, Liu S, Chen S, Qiu S, Rao Z, Liu J, Zhu S, Yan L, Mao H, Zhu Q, Quan D, Liu X. Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects. Acta Biomater 2018; 73:326-338. [PMID: 29649641 DOI: 10.1016/j.actbio.2018.04.001] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2017] [Revised: 03/29/2018] [Accepted: 04/02/2018] [Indexed: 12/24/2022]
Abstract
Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. STATEMENT OF SIGNIFICANCE Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy of decellularized nerve allograft for nerve regeneration, with limited success. Xenogeneic decellularized tissue matrices or hydrogels have been widely used for surgical applications owing to their ease of harvesting and low immunogenicity. Moreover, decellularized tissue matrix hydrogels show good biocompatibility and are highly tunable. In this study, we prepared a porcine decellularized nerve matrix (pDNM-G) and evaluated its potential for promoting nerve regeneration. Our results demonstrate that pDNM-G can support Schwann cell proliferation and peripheral nerve regeneration by means of residual primary extracellular matrix components and nano-fibrous structure features.
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Affiliation(s)
- Tao Lin
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Sheng Liu
- PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Shihao Chen
- PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Shuai Qiu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Zilong Rao
- PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Jianghui Liu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Shuang Zhu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Liwei Yan
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China
| | - Haiquan Mao
- Institute for NanoBioTechnology, and Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, USA
| | - Qingtang Zhu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China.
| | - Daping Quan
- PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China.
| | - Xiaolin Liu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Peripheral Nerve Tissue-engineering and Technology Research Center, Guangdong Provincial Functional Biomaterials Engineering Technology Research Center, Guangzhou, China.
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Du J, Chen H, Qing L, Yang X, Jia X. Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration. Biomater Sci 2018; 6:1299-1311. [PMID: 29725688 PMCID: PMC5978680 DOI: 10.1039/c8bm00260f] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Peripheral nerve injury is a common disease that affects more than 20 million people in the United States alone and remains a major burden to society. The current gold standard treatment for critical-sized nerve defects is autologous nerve graft transplantation; however, this method is limited in many ways and does not always lead to satisfactory outcomes. The limitations of autografts have prompted investigations into artificial neural scaffolds as replacements, and some neural scaffold devices have progressed to widespread clinical use; scaffold technology overall has yet to be shown to be consistently on a par with or superior to autografts. Recent advances in biomimetic scaffold technologies have opened up many new and exciting opportunities, and novel improvements in material, fabrication technique, scaffold architecture, and lumen surface modifications that better reflect biological anatomy and physiology have independently been shown to benefit overall nerve regeneration. Furthermore, biomimetic features of neural scaffolds have also been shown to work synergistically with other nerve regeneration therapy strategies such as growth factor supplementation, stem cell transplantation, and cell surface glycoengineering. This review summarizes the current state of neural scaffolds, highlights major advances in biomimetic technologies, and discusses future opportunities in the field of peripheral nerve regeneration.
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Affiliation(s)
- Jian Du
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. ; Tel: +1 410-706-5025
| | - Huanwen Chen
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. ; Tel: +1 410-706-5025
| | - Liming Qing
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. ; Tel: +1 410-706-5025
| | - Xiuli Yang
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. ; Tel: +1 410-706-5025
| | - Xiaofeng Jia
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. ; Tel: +1 410-706-5025
- Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Lin T, Qiu S, Yan L, Zhu S, Zheng C, Zhu Q, Liu X. Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury. Muscle Nerve 2018; 57:821-828. [PMID: 29211920 DOI: 10.1002/mus.26033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 11/28/2017] [Accepted: 12/02/2017] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. METHODS Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. RESULTS Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. DISCUSSION Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018.
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Affiliation(s)
- Tao Lin
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, 5180080, PR China
| | - Shuai Qiu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, 5180080, PR China
| | - Liwei Yan
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, 5180080, PR China
| | - Shuang Zhu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, 5180080, PR China
| | - Canbin Zheng
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, 5180080, PR China
| | - Qingtang Zhu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, 5180080, PR China
| | - Xiaolin Liu
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, 5180080, PR China
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Rebowe R, Rogers A, Yang X, Kundu SC, Smith TL, Li Z. Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions. J Hand Microsurg 2018; 10:61-65. [PMID: 30154617 DOI: 10.1055/s-0038-1626687] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 01/02/2018] [Indexed: 01/09/2023] Open
Abstract
Nerve conduits are becoming increasingly popular for the repair of peripheral nerve injuries. Their ease of application and lack of donor site morbidity make them an attractive option for nerve repair in many situations. Today, there are many different conduits to choose in different sizes and materials, giving the reconstructive surgeon many options for any given clinical problem. However, to properly utilize these unique reconstructive tools, the peripheral nerve surgeon must be familiar not only with their standard indications but also with their functional limitations. In this review, the authors identify the common applications of nerve conduits, expected results, and shortcomings of current techniques. Furthermore, future directions for nerve conduit use are identified.
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Affiliation(s)
- Ryan Rebowe
- Department of Orthopaedics, Wake Forest Baptist Medical Center, Winston Salem, North Carolina, United States
| | - Ashley Rogers
- Department of Orthopaedics, Wake Forest Baptist Medical Center, Winston Salem, North Carolina, United States
| | - Xuebin Yang
- Department of Oral Biology, University of Leeds, Leeds, United Kingdom
| | - S C Kundu
- Department of Biotechnology, Indian Institute of Technology, Kharagpur, West Bengal, India
| | - Thomas L Smith
- Department of Orthopaedics, Wake Forest Baptist Medical Center, Winston Salem, North Carolina, United States
| | - Zhongyu Li
- Department of Orthopaedics, Wake Forest Baptist Medical Center, Winston Salem, North Carolina, United States
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Pepper JP, Wang TV, Hennes V, Sun SY, Ichida JK. Human Induced Pluripotent Stem Cell-Derived Motor Neuron Transplant for Neuromuscular Atrophy in a Mouse Model of Sciatic Nerve Injury. JAMA FACIAL PLAST SU 2017; 19:197-205. [PMID: 27978547 DOI: 10.1001/jamafacial.2016.1544] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance Human motor neurons may be reliably derived from induced pluripotent stem cells (iPSCs). In vivo transplant studies of human iPSCs and their cellular derivatives are essential to gauging their clinical utility. Objective To determine whether human iPSC-derived motor neurons can engraft in an immunodeficient mouse model of sciatic nerve injury. Design, Setting, and Subjects This nonblinded interventional study with negative controls was performed at a biomedical research institute using an immunodeficient, transgenic mouse model. Induced pluripotent stem cell-derived motor neurons were cultured and differentiated. Cells were transplanted into 32 immunodeficient mice with sciatic nerve injury aged 6 to 15 weeks. Tissue analysis was performed at predetermined points after the mice were killed humanely. Animal experiments were performed from February 24, 2015, to May 2, 2016, and data were analyzed from April 7, 2015, to May 27, 2016. Interventions Human iPSCs were used to derive motor neurons in vitro before transplant. Main Outcomes and Measures Evidence of engraftment based on immunohistochemical analysis (primary outcome measure); evidence of neurite outgrowth and neuromuscular junction formation (secondary outcome measure); therapeutic effect based on wet muscle mass preservation and/or electrophysiological evidence of nerve and muscle function (exploratory end point). Results In 13 of the 32 mice undergoing the experiment, human iPSC-derived motor neurons successfully engrafted and extended neurites to target denervated muscle. Human iPSC-derived motor neurons reduced denervation-induced muscular atrophy (mean [SD] muscle mass preservation, 54.2% [4.0%]) compared with negative controls (mean [SD] muscle mass preservation, 33.4% [2.3%]) (P = .04). No electrophysiological evidence of muscle recovery was found. Conclusions and Relevance Human iPSC-derived motor neurons may have future use in the treatment of peripheral motor nerve injury, including facial paralysis. Level of Evidence NA.
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Affiliation(s)
- Jon-Paul Pepper
- USC (University of Southern California) Caruso Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine, USC, Los Angeles
| | - Tiffany V Wang
- USC (University of Southern California) Caruso Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine, USC, Los Angeles
| | - Valerie Hennes
- Department of Regenerative Medicine and Stem Cell Biology, Broad CIRM (California Institute for Regenerative Medicine) Center, Keck School of Medicine, USC, Los Angeles
| | - Soo Yeon Sun
- Division of Biokinesiology and Physical Therapy, Herman Ostrow School of Dentistry, USC, Los Angeles
| | - Justin K Ichida
- Department of Regenerative Medicine and Stem Cell Biology, Broad CIRM (California Institute for Regenerative Medicine) Center, Keck School of Medicine, USC, Los Angeles
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Panagopoulos GN, Megaloikonomos PD, Mavrogenis AF. The Present and Future for Peripheral Nerve Regeneration. Orthopedics 2017; 40:e141-e156. [PMID: 27783836 DOI: 10.3928/01477447-20161019-01] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 08/23/2016] [Indexed: 02/03/2023]
Abstract
Peripheral nerve injury can have a potentially devastating impact on a patient's quality of life, resulting in severe disability with substantial social and personal cost. Refined microsurgical techniques, advances in peripheral nerve topography, and a better understanding of the pathophysiology and molecular basis of nerve injury have all led to a decisive leap forward in the field of translational neurophysiology. Nerve repair, nerve grafting, and nerve transfers have improved significantly with consistently better functional outcomes. Direct nerve repair with epineural microsutures is still the surgical treatment of choice when a tension-free coaptation in a well-vascularized bed can be achieved. In the presence of a significant gap (>2-3 cm) between the proximal and distal nerve stumps, primary end-to-end nerve repair often is not possible; in these cases, nerve grafting is the treatment of choice. Indications for nerve transfer include brachial plexus injuries, especially avulsion type, with long distance from target motor end plates, delayed presentation, segmental loss of nerve function, and broad zone of injury with dense scarring. Current experimental research in peripheral nerve regeneration aims to accelerate the process of regeneration using pharmacologic agents, bioengineering of sophisticated nerve conduits, pluripotent stem cells, and gene therapy. Several small molecules, peptides, hormones, neurotoxins, and growth factors have been studied to improve and accelerate nerve repair and regeneration by reducing neuronal death and promoting axonal outgrowth. Targeting specific steps in molecular pathways also allows for purposeful pharmacologic intervention, potentially leading to a better functional recovery after nerve injury. This article summarizes the principles of nerve repair and the current concepts of peripheral nerve regeneration research, as well as future perspectives. [Orthopedics. 2017; 40(1):e141-e156.].
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Wang C, Lu CF, Peng J, Hu CD, Wang Y. Roles of neural stem cells in the repair of peripheral nerve injury. Neural Regen Res 2017; 12:2106-2112. [PMID: 29323053 PMCID: PMC5784362 DOI: 10.4103/1673-5374.221171] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.
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Affiliation(s)
- Chong Wang
- Central Hospital of Handan, Handan, Hebei Province; Institute of Orthopedics, Chinese PLA General Hospital, Beijing; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
| | - Chang-Feng Lu
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing, ; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
| | - Jiang Peng
- Institute of Orthopedics, Chinese PLA General Hospital; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Lab of Musculoskeletal Trauma & War Injuries of Chinese PLA, Beijing, China
| | - Cheng-Dong Hu
- Central Hospital of Handan, Handan, Hebei Province, China
| | - Yu Wang
- Institute of Orthopedics, Chinese PLA General Hospital; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Lab of Musculoskeletal Trauma & War Injuries of Chinese PLA, Beijing, China
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Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue–Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration–Approved Nerve Conduit. Plast Reconstr Surg 2016; 138:132-139. [DOI: 10.1097/prs.0000000000002291] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Sahyouni R, Bhatt J, Djalilian HR, Tang WC, Middlebrooks JC, Lin HW. Selective stimulation of facial muscles with a penetrating electrode array in the feline model. Laryngoscope 2016; 127:460-465. [PMID: 27312936 DOI: 10.1002/lary.26078] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Revised: 03/13/2016] [Accepted: 04/12/2016] [Indexed: 01/13/2023]
Abstract
OBJECTIVES/HYPOTHESIS Permanent facial nerve injury is a difficult challenge for both patients and physicians given its potential for debilitating functional, cosmetic, and psychological sequelae. Although current surgical interventions have provided considerable advancements in facial nerve rehabilitation, they often fail to fully address all impairments. We aim to introduce an alternative approach to facial nerve rehabilitation. STUDY DESIGN Acute experiments in animals with normal facial function. METHODS The study included three anesthetized cats. Four facial muscles (levator auris longus, orbicularis oculi, nasalis, and orbicularis oris) were monitored with a standard electromyographic (EMG) facial nerve monitoring system with needle electrodes. The main trunk of the facial nerve was exposed, and a 16-channel penetrating electrode array was placed into the nerve. Electrical current pulses were delivered to each stimulating electrode individually. Elicited EMG voltage outputs were recorded for each muscle. RESULTS Stimulation through individual channels selectively activated restricted nerve populations, resulting in selective contraction of individual muscles. Increasing stimulation current levels resulted in increasing EMG voltage responses. Typically, selective activation of two or more distinct muscles was successfully achieved via a single placement of the multi-channel electrode array by selection of appropriate stimulation channels. CONCLUSION We have established in the animal model the ability of a penetrating electrode array to selectively stimulate restricted fiber populations within the facial nerve and to selectively elicit contractions in specific muscles and regions of the face. These results show promise for the development of a facial nerve implant system. LEVEL OF EVIDENCE N/A.Laryngoscope, 2016 127:460-465, 2017.
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Affiliation(s)
- Ronald Sahyouni
- Medical Scientist Training Program, University of California, Irvine, Irvine, California, U.S.A
| | - Jay Bhatt
- Department of Otolaryngology-Head & Neck Surgery, University of California, Irvine, Irvine, California, U.S.A
| | - Hamid R Djalilian
- Department of Otolaryngology-Head & Neck Surgery, University of California, Irvine, Irvine, California, U.S.A
| | - William C Tang
- School of Medicine, Department of Biomedical Engineering, University of California, Irvine, Irvine, California, U.S.A
| | - John C Middlebrooks
- Department of Otolaryngology-Head & Neck Surgery, University of California, Irvine, Irvine, California, U.S.A
| | - Harrison W Lin
- Department of Otolaryngology-Head & Neck Surgery, University of California, Irvine, Irvine, California, U.S.A
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Leibig N, Boyle V, Kraus D, Stark GB, Penna V. Il10 and poly-dl
-lactide-ɛ-caprolactone conduits in critical size nerve defect bridging-An experimental study. Microsurgery 2015; 36:410-416. [DOI: 10.1002/micr.22423] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 04/07/2015] [Accepted: 04/10/2015] [Indexed: 12/17/2022]
Affiliation(s)
- Nico Leibig
- Department of Hand; Plastic and Reconstructive Surgery, BG Trauma Centre; Ludwigshafen Germany
| | - Veronika Boyle
- Clinic for Neurology, Ortenau Klinikum Lahr-Ettenheim; Lahr Germany
| | - Daniel Kraus
- Clinic of Plastic and Hand Surgery, University Medical Center; Freiburg Germany
| | | | - Vincenzo Penna
- Clinic of Plastic and Hand Surgery, University Medical Center; Freiburg Germany
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Update in facial nerve paralysis: tissue engineering and new technologies. Curr Opin Otolaryngol Head Neck Surg 2015; 22:291-9. [PMID: 24979369 DOI: 10.1097/moo.0000000000000062] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE OF REVIEW To present the recent advances in the treatment of facial paralysis, emphasizing the emerging technologies. This review will summarize the current state of the art in the management of facial paralysis and discuss the advances in nerve regeneration, facial reanimation, and use of novel biomaterials. This review includes surgical innovations in reinnervation and reanimation as well as progress with bioelectrical interfaces. RECENT FINDINGS The last decade has witnessed major advances in the understanding of nerve injury and approaches for management. Key innovations include strategies to accelerate nerve regeneration, provide tissue-engineered constructs that may replace nonfunctional nerves, approaches to influence axonal guidance, limiting of donor-site morbidity, and optimization of functional outcomes. Approaches to muscle transfer continue to evolve, and new technologies allow for electrical nerve stimulation and use of artificial tissues. SUMMARY The fields of biomedical engineering and facial reanimation increasingly intersect, with innovative surgical approaches complementing a growing array of tissue engineering tools. The goal of treatment remains the predictable restoration of natural facial movement, with acceptable morbidity and long-term stability. Advances in bioelectrical interfaces and nanotechnology hold promise for widening the window for successful treatment intervention and for restoring both lost neural inputs and muscle function.
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Zhang PX, Li-Ya A, Kou YH, Yin XF, Xue F, Han N, Wang TB, Jiang BG. Biological conduit small gap sleeve bridging method for peripheral nerve injury: regeneration law of nerve fibers in the conduit. Neural Regen Res 2015; 10:71-8. [PMID: 25788923 PMCID: PMC4357121 DOI: 10.4103/1673-5374.150709] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/14/2014] [Indexed: 11/04/2022] Open
Abstract
The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair peripheral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good histocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration (2-8 weeks), the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objective and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury.
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Affiliation(s)
- Pei-Xun Zhang
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
| | - A Li-Ya
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
| | - Yu-Hui Kou
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
| | - Xiao-Feng Yin
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
| | - Feng Xue
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
| | - Na Han
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
| | - Tian-Bing Wang
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
| | - Bao-Guo Jiang
- Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, China
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Nerve Gaps. Plast Reconstr Surg 2014. [DOI: 10.1097/prs.0000000000000243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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