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Hamour HM, Marangoz AH, Altun G, Kaplan S. Neuroprotective effects of Garcinia kolaand curcumin on diabetic transected sciatic nerve. Biomed Mater 2025; 20:035025. [PMID: 40267944 DOI: 10.1088/1748-605x/adcfe3] [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: 12/21/2024] [Accepted: 04/23/2025] [Indexed: 04/25/2025]
Abstract
The growing interest in peripheral nerve regeneration and developing post-traumatic repair methods under diabetes was the impetus for this study, which aims to investigate the effect of curcumin andGarcinia kola(GK) on the transected and diabetic sciatic nerves. Thirty-five male Wistar albino rats were used. The animals were divided into five groups; each consisted of seven rats. The sciatic nerve was transected in all groups of rats except the control (Cont) group, which underwent no treatment. In the transected animals, a 10 mm nerve stump was removed from the 2 cm distal to the sciatic notch. The external jugular vein was used as a conduit to repair the gap between the two ends of the sciatic nerve. Diabetes was induced in the transected + diabetes mellitus (T + DM), the transected + diabetes mellitus + GK (T + DM + GK), and the transected + diabetes mellitus + Curcumin (T + DM + Cur) groups except for the sham group. A dose of 300 mg kg-1d-1of curcumin dissolved in olive oil was administered to the T + DM + Cur group (via oral gavage every day for 28 d) and 200 mg kg-1d-1of GK to the T + DM + GK group (via oral gavage every day for 7 d). All animals were sacrificed after three months. Stereological analysis and functional and microscopic evaluations were done to evaluate the sciatic nerve regeneration and function. In the T + DM + GK and the sham groups, the number of axons increased. A slight improvement in the axonal area in the T + DM + Cur and the sham groups was also observed, and an increase in the myelin sheath thickness was found in the T + DM + GK and the sham group. When the SFI test results were evaluated, it was seen that GK had a stronger effect than curcumin in terms of functional regeneration. Additionally, no significant difference was observed between T + DM and Cont groups when the electrophysiological results were examined. The study showed GK's efficiency in treating diabetic peripheral nerve regeneration.
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Affiliation(s)
- Hala Mahgoub Hamour
- Department of Histology and Embryology, Ondokuz Mayıs University, Samsun, Turkey
| | | | - Gamze Altun
- Department of Histology and Embryology, Ondokuz Mayıs University, Samsun, Turkey
| | - Süleyman Kaplan
- Department of Histology and Embryology, Ondokuz Mayıs University, Samsun, Turkey
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2
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Eisenberg MT, Hustedt JW. Alginate Use in Orthopedics and Peripheral Nerve Repair: A Systematic Review. Cureus 2024; 16:e72480. [PMID: 39502971 PMCID: PMC11536484 DOI: 10.7759/cureus.72480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2024] [Indexed: 11/08/2024] Open
Abstract
The use of alginate, a derivative of seaweed, has been proposed for multiple orthopedic indications. We aimed to review the current use of alginate in orthopedics and to focus on the future applications of alginate for peripheral nerve repair. A comprehensive literature search was performed to identify biomechanical, laboratory, animal, and human studies where alginate has been utilized for orthopedic or nerve repair indications. A systematic review of orthopedic indications was conducted for safety and efficacy, and a specific focus was placed on alginate for use in peripheral nerve repair and reconstruction. Thirty-two studies were identified. Alginate has a strong history and safety profile for usage in orthopedic surgery. Its primary usage has been for the repair of articular cartilage, although it has also been used for disc regeneration of the lumbar spine and for cushioning joints in osteoarthritis. The primary indication in peripheral nerve repair is to create an environment that encourages Schwann cell migration and repair in nerve injuries while blocking fibrotic scar tissue formation by inhibiting the activity of fibroblasts. Alginate hydrogel may serve as a potential conduit for nerve regeneration in nerve injuries with small to medium-sized gaps.
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Affiliation(s)
- Matthew T Eisenberg
- Orthopedic Surgery, University of Arizona College of Medicine - Phoenix, Phoenix, USA
| | - Joshua W Hustedt
- Hand Surgery, University of Arizona College of Medicine - Phoenix, Phoenix, USA
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3
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Kupczyk EK, Jakubietz RG, Paul MM, Schäfer S, Hölscher-Doht S. [A child's severe injury of the palm hand - challenges and opportunities]. HANDCHIR MIKROCHIR P 2024; 56:388-391. [PMID: 38857620 DOI: 10.1055/a-2234-0049] [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: 06/12/2024] Open
Abstract
Die Versorgung kindlicher traumatischer Hand- und Fingerverletzungen stellt in der
Handchirurgie eine besondere Herausforderung dar. Da solch komplexe Verletzungen
vergleichsweise selten sind 1, gibt es im
Gegensatz zu vergleichbaren Verletzungsmustern beim Erwachsenen kein genauso
etabliertes und allgemeingültiges Nachbehandlungskonzept 2
3.
Zusätzlich muss das Kind als Individuum immer gemeinsam mit den Eltern auf die
nächsten Schritte vorbereitet werden 1
3
4.
Die klinische Untersuchung ist zudem aufgrund der altersabhängig eingeschränkten
Mitarbeit der jungen Patienten erschwert 1
3. Um bestmögliche Resultate zu
erreichen, sind besondere Fähigkeiten in der Kommunikation Voraussetzung 4. Speziell die kleine Anatomie stellt
zusätzlich hohe Anforderungen an die Fertigkeiten des Operateurs.
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Affiliation(s)
- Eva K Kupczyk
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Rafael G Jakubietz
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Mila M Paul
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Susanne Schäfer
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Stefanie Hölscher-Doht
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie, Universitätsklinikum Würzburg, Würzburg, Germany
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4
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Wang S, Wen X, Fan Z, Ding X, Wang Q, Liu Z, Yu W. Research advancements on nerve guide conduits for nerve injury repair. Rev Neurosci 2024; 35:627-637. [PMID: 38517315 DOI: 10.1515/revneuro-2023-0093] [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: 08/23/2023] [Accepted: 11/19/2023] [Indexed: 03/23/2024]
Abstract
Peripheral nerve injury (PNI) is one of the most serious causes of disability and loss of work capacity of younger individuals. Although PNS has a certain degree of regeneration, there are still challenges like disordered growth, neuroma formation, and incomplete regeneration. Regarding the management of PNI, conventional methods such as surgery, pharmacotherapy, and rehabilitative therapy. Treatment strategies vary depending on the severity of the injury. While for the long nerve defect, autologous nerve grafting is commonly recognized as the preferred surgical approach. Nevertheless, due to lack of donor sources, neurological deficits and the low regeneration efficiency of grafted nerves, nerve guide conduits (NGCs) are recognized as a future promising technology in recent years. This review provides a comprehensive overview of current treatments for PNI, and discusses NGCs from different perspectives, such as material, design, fabrication process, and composite function.
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Affiliation(s)
- Shoushuai Wang
- China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun City 130033, Jilin Province, China
| | - Xinggui Wen
- China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun City 130033, Jilin Province, China
| | - Zheyuan Fan
- China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun City 130033, Jilin Province, China
| | - Xiangdong Ding
- China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun City 130033, Jilin Province, China
| | - Qianqian Wang
- China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun City 130033, Jilin Province, China
| | - Zhongling Liu
- China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun City 130033, Jilin Province, China
| | - Wei Yu
- China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun City 130033, Jilin Province, China
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5
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Azapagic A, Agarwal J, Gale B, Shea J, Wojtalewicz S, Sant H. A tacrolimus-eluting nerve guidance conduit enhances regeneration in a critical-sized peripheral nerve injury rat model. Biomed Microdevices 2024; 26:34. [PMID: 39102047 DOI: 10.1007/s10544-024-00717-y] [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] [Accepted: 07/22/2024] [Indexed: 08/06/2024]
Abstract
Critical-sized peripheral nerve injuries pose a significant clinical challenge and lead to functional loss and disability. Current regeneration strategies, including autografts, synthetic nerve conduits, and biologic treatments, encounter challenges such as limited availability, donor site morbidity, suboptimal recovery, potential immune responses, and sustained stability and bioactivity. An obstacle in peripheral nerve regeneration is the immune response that can lead to inflammation and scarring that impede the regenerative process. Addressing both the immunological and regenerative needs is crucial for successful nerve recovery. Here, we introduce a novel biodegradable tacrolimus-eluting nerve guidance conduit engineered from a blend of poly (L-lactide-co-caprolactone) to facilitate peripheral nerve regeneration and report the testing of this conduit in 15-mm critical-sized gaps in the sciatic nerve of rats. The conduit's diffusion holes enable the local release of tacrolimus, a potent immunosuppressant with neuro-regenerative properties, directly into the injury site. A series of in vitro experiments were conducted to assess the ability of the conduit to maintain a controlled tacrolimus release profile that could promote neurite outgrowth. Subsequent in vivo assessments in rat models of sciatic nerve injury revealed significant enhancements in nerve regeneration, as evidenced by improved axonal growth and functional recovery compared to controls using placebo conduits. These findings indicate the synergistic effects of combining a biodegradable conduit with localized, sustained delivery of tacrolimus, suggesting a promising approach for treating peripheral nerve injuries. Further optimization of the design and long-term efficacy studies and clinical trials are needed before the potential for clinical translation in humans can be considered.
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Affiliation(s)
- Azur Azapagic
- Department of Mechanical Engineering, The University of Utah, 1495 E 100 S, Salt Lake City, UT, 84112, USA.
| | - Jayant Agarwal
- Department of Surgery, Division of Plastic Surgery, The University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT, 84132, USA
| | - Bruce Gale
- Department of Mechanical Engineering, The University of Utah, 1495 E 100 S, Salt Lake City, UT, 84112, USA
| | - Jill Shea
- Department of Surgery, The University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT, 84132 , USA
- Department of Biomedical Engineering, The University of Utah, 1495 E 100 S, Salt Lake City, UT, 84112, USA
| | - Susan Wojtalewicz
- Department of Surgery, The University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT, 84132 , USA
| | - Himanshu Sant
- Department of Chemical Engineering, The University of Utah, 1495 E 100 S, Salt Lake City, UT, 84112, USA
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Ashna M, Senthilkumar N, Sanpui P. Human Hair Keratin-Based Hydrogels in Regenerative Medicine: Current Status and Future Directions. ACS Biomater Sci Eng 2023; 9:5527-5547. [PMID: 37734053 DOI: 10.1021/acsbiomaterials.3c00883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/23/2023]
Abstract
Regenerative medicine (RM) is a multidisciplinary field that utilizes the inherent regenerative potential of human cells to generate functionally and physiologically acceptable human cells, tissues, and organs in vivo or ex vivo. An appropriate biomaterial scaffold with desired physicochemical properties constitutes an important component of a successful RM approach. Among various forms of biomaterials explored until the present day, hydrogels have emerged as a versatile candidate for tissue engineering and regenerative medicine (TERM) applications such as scaffolds for spatial patterning and delivering therapeutic agents, or substrates to enhance cell growth, differentiation, and migration. Although hydrogels can be prepared from a variety of synthetic polymers as well as biopolymers, the latter are preferred for their inherent biocompatibility. Specifically, keratins are fibrous proteins that have been recently explored for constructing hydrogels useful for RM purposes. The present review discusses the suitability of keratin-based biomaterials in RM, with a particular focus on human hair keratin hydrogels and their use in various RM applications.
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Affiliation(s)
- Mymuna Ashna
- Department of Biotechnology, BITS Pilani Dubai Campus, Dubai International Academic City, Dubai, United Arab Emirates
| | - Neeharika Senthilkumar
- Department of Biotechnology, BITS Pilani Dubai Campus, Dubai International Academic City, Dubai, United Arab Emirates
| | - Pallab Sanpui
- Department of Biotechnology, BITS Pilani Dubai Campus, Dubai International Academic City, Dubai, United Arab Emirates
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7
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Dahlin E, Gudinge H, Dahlin LB, Nyman E. Neuromas cause severe residual problems at long-term despite surgery. Sci Rep 2023; 13:15693. [PMID: 37735475 PMCID: PMC10514298 DOI: 10.1038/s41598-023-42245-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 09/07/2023] [Indexed: 09/23/2023] Open
Abstract
Pain, and disabilities after neuroma surgery, using patient reported outcome measurements (PROMs), were evaluated by QuickDASH and a specific Hand Questionnaire (HQ-8). The 69 responding individuals (response rate 61%; 59% women; 41% men; median follow up 51 months) reported high QuickDASH score, pain on load, cold sensitivity, ability to perform daily activities and sleeping difficulties. Individuals reporting impaired ability to perform daily activities and sleeping problems had higher scores for pain, stiffness, weakness, numbness/tingling, cold sensitivity and QuickDASH. Only 17% of individuals reported no limitations at all. No differences were observed between sexes. Surgical methods did not influence outcome. Symptoms and disabilities correlated moderately-strongly to each other and to ability to perform regular daily activities as well as to sleeping difficulties. Pain, cold sensitivity, sleeping difficulties and limitation to perform daily activities were associated to higher QuickDASH. A weak association was found between follow up time and QuickDASH score as well as pain on load, but not cold sensitivity. A major nerve injury was frequent among those with limitations during work/performing other regular daily activities. Despite surgical treatment, neuromas cause residual problems, which affect the capacity to perform daily activities and ability to sleep with limited improvement in long-term.
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Affiliation(s)
- Emma Dahlin
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
- Department of Translational Medicine-Hand Surgery, Lund University, Jan Waldenströms gata 5, 20502, Malmö, Sweden.
- Varberg Hospital, Region Halland, Varberg, Sweden.
| | - Hanna Gudinge
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Department of Translational Medicine-Hand Surgery, Lund University, Jan Waldenströms gata 5, 20502, Malmö, Sweden
| | - Lars B Dahlin
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Department of Translational Medicine-Hand Surgery, Lund University, Jan Waldenströms gata 5, 20502, Malmö, Sweden
- Department of Hand Surgery, Skåne University Hospital, Malmö, Sweden
| | - Erika Nyman
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Department of Hand Surgery, Plastic Surgery and Burns, Linköping University Hospital, Linköping, Sweden
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8
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Lecoq FA, Barnouin L, Ardouin L, Hartmann D, Obert L. Inverted human umbilical artery as a 3D scaffold for sciatic nerve regeneration in rats. Cell Tissue Bank 2022; 23:909-922. [PMID: 35503142 PMCID: PMC9675695 DOI: 10.1007/s10561-022-10006-8] [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: 10/29/2021] [Accepted: 04/03/2022] [Indexed: 11/02/2022]
Abstract
Treatment of peripheral nerve injuries (PNIs) remains a challenge. Interposing a graft delivers better regenerative outcomes. Autografts present major drawbacks which have given rise to the development of alternatives such as artificial scaffolds, some of which are very promising. This study was designed to investigate the potential use of an inverted human umbilical cord artery (iHUA) as a 3D scaffold nerve chamber, for nerve regeneration after transection of the sciatic nerve (SN) in rats. Rats underwent surgical SN transection in their right hindlimb, followed by suture of the device at the resected stumps. Local tolerance, insert biodegradability and nerve reconstruction over time were thoroughly studied by histopathological and morphometric analysis, completed by functional test assessment of sensitivity and motricity recovery. We have demonstrated that nerve reconstruction in the presence of an iHUA insert is effective. The device is well tolerated and highly biodegraded. Although the regenerated nerve is still immature at the end of our study, signs of sensitivity and partial functional recovery were witnessed, confirming our histological findings. Our results support the potential clinical use of iHUA as a 3D scaffold to bridge nerve discontinuity and guide axonal regrowth in selected cases of PNIs.
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Affiliation(s)
- Flore-Anne Lecoq
- Institut de la Main Nantes Atlantique, Elsan Santé Atlantique, Saint Herblain, France
| | | | - Ludovic Ardouin
- Institut de la Main Nantes Atlantique, Elsan Santé Atlantique, Saint Herblain, France
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9
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Li X, Zhang X, Hao M, Wang D, Jiang Z, Sun L, Gao Y, Jin Y, Lei P, Zhuo Y. The application of collagen in the repair of peripheral nerve defect. Front Bioeng Biotechnol 2022; 10:973301. [PMID: 36213073 PMCID: PMC9542778 DOI: 10.3389/fbioe.2022.973301] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve injury to promote peripheral nerve regeneration. Moreover, its biological properties, such as low immunogenicity, excellent biocompatibility, and biodegradability make it a suitable biomaterial for peripheral nerve repair. Collagen provides a suitable microenvironment to support Schwann cells’ growth, proliferation, and migration, thereby improving the regeneration and functional recovery of peripheral nerves. This review aims to summarize the characteristics of collagen as a biomaterial, analyze its role in peripheral nerve regeneration, and provide a detailed overview of the recent advances concerning the optimization of collagen nerve conduits in terms of physical properties and structure, as well as the application of the combination with the bioactive component in peripheral nerve regeneration.
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Affiliation(s)
- Xiaolan Li
- Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiang Zhang
- Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Ming Hao
- School of Acupuncture-Moxi Bustion and Tuina, Changchun University of Chinese Medicine, Changchun, China
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Dongxu Wang
- Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China
| | - Ziping Jiang
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Liqun Sun
- Department of Pediatrics, First Hospital of Jilin University, Changchun, China
| | - Yongjian Gao
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ye Jin
- Department of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Peng Lei
- Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Peng Lei, ; Yue Zhuo,
| | - Yue Zhuo
- School of Acupuncture-Moxi Bustion and Tuina, Changchun University of Chinese Medicine, Changchun, China
- *Correspondence: Peng Lei, ; Yue Zhuo,
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10
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Hydrogel, Electrospun and Composite Materials for Bone/Cartilage and Neural Tissue Engineering. MATERIALS 2021; 14:ma14226899. [PMID: 34832300 PMCID: PMC8624846 DOI: 10.3390/ma14226899] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/09/2021] [Accepted: 11/11/2021] [Indexed: 12/15/2022]
Abstract
Injuries of the bone/cartilage and central nervous system are still a serious socio-economic problem. They are an effect of diversified, difficult-to-access tissue structures as well as complex regeneration mechanisms. Currently, commercially available materials partially solve this problem, but they do not fulfill all of the bone/cartilage and neural tissue engineering requirements such as mechanical properties, biochemical cues or adequate biodegradation. There are still many things to do to provide complete restoration of injured tissues. Recent reports in bone/cartilage and neural tissue engineering give high hopes in designing scaffolds for complete tissue regeneration. This review thoroughly discusses the advantages and disadvantages of currently available commercial scaffolds and sheds new light on the designing of novel polymeric scaffolds composed of hydrogels, electrospun nanofibers, or hydrogels loaded with nano-additives.
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11
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Carnicer-Lombarte A, Chen ST, Malliaras GG, Barone DG. Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics. Front Bioeng Biotechnol 2021; 9:622524. [PMID: 33937212 PMCID: PMC8081831 DOI: 10.3389/fbioe.2021.622524] [Citation(s) in RCA: 185] [Impact Index Per Article: 46.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 03/19/2021] [Indexed: 12/04/2022] Open
Abstract
The implantation of any foreign material into the body leads to the development of an inflammatory and fibrotic process-the foreign body reaction (FBR). Upon implantation into a tissue, cells of the immune system become attracted to the foreign material and attempt to degrade it. If this degradation fails, fibroblasts envelop the material and form a physical barrier to isolate it from the rest of the body. Long-term implantation of medical devices faces a great challenge presented by FBR, as the cellular response disrupts the interface between implant and its target tissue. This is particularly true for nerve neuroprosthetic implants-devices implanted into nerves to address conditions such as sensory loss, muscle paralysis, chronic pain, and epilepsy. Nerve neuroprosthetics rely on tight interfacing between nerve tissue and electrodes to detect the tiny electrical signals carried by axons, and/or electrically stimulate small subsets of axons within a nerve. Moreover, as advances in microfabrication drive the field to increasingly miniaturized nerve implants, the need for a stable, intimate implant-tissue interface is likely to quickly become a limiting factor for the development of new neuroprosthetic implant technologies. Here, we provide an overview of the material-cell interactions leading to the development of FBR. We review current nerve neuroprosthetic technologies (cuff, penetrating, and regenerative interfaces) and how long-term function of these is limited by FBR. Finally, we discuss how material properties (such as stiffness and size), pharmacological therapies, or use of biodegradable materials may be exploited to minimize FBR to nerve neuroprosthetic implants and improve their long-term stability.
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Affiliation(s)
- Alejandro Carnicer-Lombarte
- Electrical Engineering Division, Department of Engineering, University of Cambridge, Cambridge, United Kingdom
| | - Shao-Tuan Chen
- Electrical Engineering Division, Department of Engineering, University of Cambridge, Cambridge, United Kingdom
| | - George G. Malliaras
- Electrical Engineering Division, Department of Engineering, University of Cambridge, Cambridge, United Kingdom
| | - Damiano G. Barone
- Electrical Engineering Division, Department of Engineering, University of Cambridge, Cambridge, United Kingdom
- Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
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Mendibil X, González-Pérez F, Bazan X, Díez-Ahedo R, Quintana I, Rodríguez FJ, Basnett P, Nigmatullin R, Lukasiewicz B, Roy I, Taylor CS, Glen A, Claeyssens F, Haycock JW, Schaafsma W, González E, Castro B, Duffy P, Merino S. Bioresorbable and Mechanically Optimized Nerve Guidance Conduit Based on a Naturally Derived Medium Chain Length Polyhydroxyalkanoate and Poly(ε-Caprolactone) Blend. ACS Biomater Sci Eng 2021; 7:672-689. [DOI: 10.1021/acsbiomaterials.0c01476] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Xabier Mendibil
- Tekniker, Basque Research and Technology Alliance (BRTA), C/ Iñaki Goenaga 5, 20600 Eibar, Spain
| | - Francisco González-Pérez
- Laboratory of Molecular Neurology, Hospital Nacional de Parapléjicos, Finca La Peraleda S/n, 45071 Toledo, Spain
| | - Xabier Bazan
- Tekniker, Basque Research and Technology Alliance (BRTA), C/ Iñaki Goenaga 5, 20600 Eibar, Spain
| | - Ruth Díez-Ahedo
- Tekniker, Basque Research and Technology Alliance (BRTA), C/ Iñaki Goenaga 5, 20600 Eibar, Spain
| | - Iban Quintana
- Tekniker, Basque Research and Technology Alliance (BRTA), C/ Iñaki Goenaga 5, 20600 Eibar, Spain
| | - Francisco Javier Rodríguez
- Laboratory of Molecular Neurology, Hospital Nacional de Parapléjicos, Finca La Peraleda S/n, 45071 Toledo, Spain
| | - Pooja Basnett
- School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, U.K
| | - Rinat Nigmatullin
- School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, U.K
| | - Barbara Lukasiewicz
- School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, U.K
| | - Ipsita Roy
- Department of Materials Science and Engineering, The University of Sheffield, Sheffield S3 7HQ, U.K
| | - Caroline S. Taylor
- Department of Materials Science and Engineering, The University of Sheffield, Sheffield S3 7HQ, U.K
| | - Adam Glen
- Department of Materials Science and Engineering, The University of Sheffield, Sheffield S3 7HQ, U.K
| | - Frederik Claeyssens
- Department of Materials Science and Engineering, The University of Sheffield, Sheffield S3 7HQ, U.K
| | - John W. Haycock
- Department of Materials Science and Engineering, The University of Sheffield, Sheffield S3 7HQ, U.K
| | - Wandert Schaafsma
- Histocell S.L., Parque Tecnológico de Bizkaia, 801 A, 2, 48160 Derio, Spain
| | - Eva González
- Histocell S.L., Parque Tecnológico de Bizkaia, 801 A, 2, 48160 Derio, Spain
| | - Begoña Castro
- Histocell S.L., Parque Tecnológico de Bizkaia, 801 A, 2, 48160 Derio, Spain
| | - Patrick Duffy
- Ashland Specialties Ireland, Synergy Centre, Dublin Road, Petitswood Mullingar, Co. Westmeath N91 F6PD, Ireland
| | - Santos Merino
- Tekniker, Basque Research and Technology Alliance (BRTA), C/ Iñaki Goenaga 5, 20600 Eibar, Spain
- Departamento de Electricidad y Electrónica, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spain
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Comparing Processed Nerve Allografts and Assessing Their Capacity to Retain and Release Nerve Growth Factor. Ann Plast Surg 2019; 81:198-202. [PMID: 29781850 DOI: 10.1097/sap.0000000000001464] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Peripheral nerve gap injuries continue to present a clinical challenge to today's surgeons. One method of surgical repair, implantation of acellular allografts, has been developed with the aim of bridging the gap with a cadaveric graft after removal of its cellular components, thereby accelerating axonal regeneration and eliminating the need for immunosuppression in recipient patients. Although decellularizing allografts reduces rates of graft rejection, the same chemical processing modifies the neural microenvironment, removing neutrotrophic factors and modifying the complex extracellular matrix. In this study, we explore 3 common methods for producing acellular allografts. Extracellular matrix content remaining after processing was investigated and was found to be highly dependent on the decellularization method. In addition, scanning electron micrographs were obtained to evaluate the structural effects of the decellularization methods. Though the content and structure of these processed allografts will contribute to their effectiveness as nerve gap repair candidates, we demonstrate that it also affects their capacity to be supplemented/preloaded with the prototypical neurotrophin, nerve growth factor (NGF), essential to neuronal regeneration. Although all allografts had some capacity for retaining NGF in the first 24 hours, only Sondell-processed grafts retained NGF over the entire experimental period of 21 days. Future studies will include validating these processed and supplemented allografts as viable alternatives to traditional autograft nerve gap repair.
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Li L, He WT, Qin BG, Liu XL, Yang JT, Gu LQ. Comparison between direct repair and human acellular nerve allografting during contralateral C7 transfer to the upper trunk for restoration of shoulder abduction and elbow flexion. Neural Regen Res 2019; 14:2132-2140. [PMID: 31397352 PMCID: PMC6788224 DOI: 10.4103/1673-5374.262600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system; meaningful recovery was defined as M3–M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restoration of shoulder abduction and elbow flexion. Thus, if direct coaptation is not possible, use of acellular nerve allografts is a suitable option. This study was approved by the Medical Ethical Committee of the First Affiliated Hospital of Sun Yat-sen University, China (Application ID: [2017] 290) on November 14, 2017.
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Affiliation(s)
- Liang Li
- Department of Orthopedic Trauma and Microsurgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Wen-Ting He
- Department of Orthopedic Trauma and Microsurgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Ben-Gang Qin
- Department of Orthopedic Trauma and Microsurgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Xiao-Lin Liu
- Department of Orthopedic Trauma and Microsurgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Jian-Tao Yang
- Department of Orthopedic Trauma and Microsurgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Li-Qiang Gu
- Department of Orthopedic Trauma and Microsurgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
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Guo J, Low JH, Wong YR, Yeow CH. Design and Evaluation of a Novel Hybrid Soft Surgical Gripper for Safe Digital Nerve Manipulation. MICROMACHINES 2019; 10:E190. [PMID: 30875954 PMCID: PMC6471026 DOI: 10.3390/mi10030190] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/07/2019] [Accepted: 03/12/2019] [Indexed: 01/09/2023]
Abstract
Forceps are essential tools for digital nerve manipulation during digital nerve repair surgery. However, surgeons have to operate forceps with extreme caution to prevent detrimental post-operative complications caused by over-gripping force. Their intrinsically safe characteristics have led to the increasing adoption of soft robotics in various biomedical applications. In this paper, a miniaturized hybrid soft surgical gripper is proposed for safe nerve manipulation in digital nerve repair surgery. This new surgical gripper includes a soft inflatable actuator and a gripper shell with a hook-shaped structure. The ability to achieve a compliant grip and safe interaction with digital nerves is provided by the inflated soft pneumatic actuator, while the rigid hook retractor still allows surgeons to scoop up the nerve from its surrounding tissues during surgery. The performance of the proposed surgical gripper was evaluated by the contact/pulling force sensing experiments and deformation measurement experiments. In the cadaver experiments, this new surgical gripper was able to complete the required nerve manipulation within the limited working space. The average deformation of the digital nerve with an average diameter of 1.45 mm gripped by the proposed surgical gripper is less than 0.22 mm. The average deformity is less than 15% of its original diameter.
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Affiliation(s)
- Jin Guo
- Department of Biomedical Engineering, National University of Singapore, Singapore 119077, Singapore.
| | - Jin-Huat Low
- Advanced Robotics Centre, National University of Singapore, Singapore 119077, Singapore.
| | - Yoke-Rung Wong
- Biomechanics Laboratory, Singapore General Hospital, Singapore 169856, Singapore.
| | - Chen-Hua Yeow
- Department of Biomedical Engineering, National University of Singapore, Singapore 119077, Singapore.
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Conduit-based Nerve Repairs Provide Greater Resistance to Tension Compared with Primary Repairs: A Biomechanical Analysis on Large Animal Samples. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2018; 6:e1981. [PMID: 30656099 PMCID: PMC6326599 DOI: 10.1097/gox.0000000000001981] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 08/24/2018] [Indexed: 11/29/2022]
Abstract
Background: When primary repair of transected peripheral nerves is not possible due to large gaps, nerve grafts or repair using conduits are other options to bridge the gap such that the nerve is repaired without tension. When nerve gaps are repaired primarily, there is a worry about tension, failure, and poor healing. In this biomechanical study comparing nerves repaired primarily versus those repaired with conduits, we hypothesized that conduit repair provided greater mechanical breaking strength. Methods: We dissected fresh cadaveric sheep hooves and transacted their peripheral nerves. Subsequently, we divided these transacted nerves into 2 groups: primary repair versus repair using a nerve conduit. After repair using a standardized technique, we tensioned each of these repairs via a load tester and recorded the force required till repair failure occurred. Results: Six nerves using primary nerve repair and 6 nerves repaired with a nerve conduit (10 mm length × 2.5 mm diameter) were studied. The average breaking strength of the nerves repaired with the nerve conduit was 0.92 N and that using the primary nerve repair technique was 0.46 N (P = 0.001). All the nerves repaired using nerve conduit repair had an additional 5 mm added to their total length as compared with the nerves in the other group. Conclusions: Nerve repair using a nerve conduit ensures a higher breaking strength and potentially a greater tension-free repair as compared with primary nerve repairs in a sheep model. This study supports the use of conduits in the bridging of nerve gaps.
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Karamanos E, Rakitin I, Dream S, Siddiqui A. Nerve Transfer Surgery for Penetrating Upper Extremity Injuries. Perm J 2018; 22:17-156. [PMID: 29702048 DOI: 10.7812/tpp/17-156] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
CONTEXT Nerve transfer surgery is an option for repair of penetrating injuries of the upper extremity. In the right setting, it has advantages over tendon transfers and nerve grafting. OBJECTIVE To review our experience since 2006 of nerve transfer surgery in the upper extremities. DESIGN We included cases performed to repair penetrating trauma within three months of injury with at least three years' follow-up. MAIN OUTCOME MEASURES Preoperative and postoperative muscle strength of the affected extremity. RESULTS All 16 patients were males aged 16 to 43 years. Six patients underwent nerve transfer surgery because of elbow flexion; 5, finger extension; 3, finger flexion; and 2, wrist pronation. Nine patients (56%) had associated vascular injury, and 4 (25%) had fractures. Average follow-up was 6 years. No perioperative complications occurred. Patients had a mean of 3.7 operations after the initial trauma. All patients received physical therapy. All patients improved from 0 of 5 muscle strength preoperatively to a mean of 3.8 (range = 2/5 to 5/5) within 1 year after surgery. In all cases, strength was maintained, and 8 (50%) had continued improvement after Year 1. Ten (63%) returned to their previous employment level. Mean Disabilities of the Arm, Shoulder and Hand score improved from 68 to 83 postoperatively. CONCLUSION Nerve transfer is a safe, effective technique for correcting penetrating trauma-related nerve injury. In appropriate patients it offers advantages over other techniques. Outcomes can be maintained long term, and many patients can return to their previous level of function.
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Affiliation(s)
| | | | | | - Aamir Siddiqui
- Plastic and Reconstructive Surgeon at Henry Ford Hospital in Detroit, MI.
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Labroo P, Shea J, Edwards K, Ho S, Davis B, Sant H, Goodwin I, Gale B, Agarwal J. Novel drug delivering conduit for peripheral nerve regeneration. J Neural Eng 2018; 14:066011. [PMID: 28829045 DOI: 10.1088/1741-2552/aa867d] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE This paper describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA) based nerve guide conduit for controlled local delivery of nerve growth factor (NGF) and application in peripheral nerve gap injury. APPROACH An NGF dosage curve was acquired to determine the minimum in vitro concentration for optimal neurite outgrowth of dorsal root ganglion (DRG) cells; PLGA based drug delivery devices were then designed and tested in vitro and in vivo across 15 mm rat sciatic nerve gap injury model. MAIN RESULTS The drug delivery nerve guide was able to release NGF for 28 d at concentrations (0.1-10 ng ml-1) that were shown to enhance DRG neurite growth. Furthermore, the released NGF was bioactive and able to enhance DRG neurite growth. Following these tests, optimized NGF-releasing nerve conduits were implanted across 15 mm sciatic nerve gaps in a rat model, where they demonstrated significant myelination and muscle innervation in vivo as compared to empty nerve conduits (p < 0.05). This drug delivery nerve guide can release NGF for extended periods of time and enhance axon growth in vitro and in vivo and has the potential to improve nerve regeneration following a peripheral nerve injury. SIGNIFICANCE This integrated drug delivering nerve guide simplifies the design process and provides increased versatility for releasing a variety of different growth factors. This innovative device has the potential for broad applicability and allows for easier customization to change the type of drugs and dosage of individual drugs without devising a completely new biomaterial-drug conjugate each time.
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Affiliation(s)
- Pratima Labroo
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT 84112, United States of America
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Sun Y, Zhang R, Mao X, Zhang M. [Research of acellular xenogeneic nerve combined with adipose-derived stem cells and platelet rich plasma in repair of rabbit facial nerve injury]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2018; 32:736-744. [PMID: 29905054 DOI: 10.7507/1002-1892.201711079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective To investigate the early effects of acellular xenogeneic nerve combined with adipose-derived stem cells (ADSCs) and platelet rich plasma (PRP) in repairing facial nerve injury in rabbits. Methods The bilateral sciatic nerves of 15 3-month-old male Sprague-Dawley rats were harvested and decellularized as xenografts. The allogeneic ADSCs were extracted from the neck and back fat pad of healthy adult New Zealand rabbits with a method of digestion by collagenase type Ⅰ and the autologous PRP was prepared by two step centrifugation. The 3rd generation ADSCs with good growth were labelled with CM-Dil living cell stain, and the labelling and fluorescence attenuation of the cells were observed by fluorescence microscope. Another 32 New Zealand rabbits were randomly divided into 4 groups and established the left facial nerve defect in length of 1 cm ( n=8). The nerve defects of groups A, B, C, and D were repaired with CM-Dil-ADSCs composite xenogeneic nerve+autologous PRP, CM-Dil-ADSCs composite xenogeneic nerve, xenogeneic nerve, and autologous nerve, respectively. At 1 and 8 weeks after operation, the angle between the upper lip and the median line of the face (angle θ) was measured. At 4 and 8 weeks after operation, the nerve conduction velocity was recorded by electrophysiological examination. At 8 weeks after operation, the CM-Dil-ADSCs at the distal and proximal ends of regenerative nerve graft segment in groups A and B were observed by fluorescence microscopy; after toluidine blue staining, the number of myelinated nerve fibers in regenerated nerve was calculated; the structure of regenerated nerve fibers was observed by transmission electron microscope. Results ADSCs labelled by CM-Dil showed that the labelling rate of cells was more than 90% under fluorescence microscope, and the labelled cells proliferated well, and the fluorescence attenuated slightly after passage. All the animals survived after operation, the incision healed well and no infection occurred. At 1 week after operation, all the animals in each group had different degrees of dysfunction. The angle θ of the left side in groups A, B, C, and D were (53.4±2.5), (54.0±2.6), (53.7±2.4), and (53.0±2.1)°, respectively; showing significant differences when compared with the healthy sides ( P<0.05). At 8 weeks after operation, the angle θ of the left side in groups A, B, C, and D were (61.9±4.7), (56.8±4.2), (54.6±3.8), and (63.8±5.8)°, respectively; showing significant differences when compared with the healthy sides and with the values at 1 week ( P<0.05). Gross observation showed that the integrity and continuity of regenerated nerve in 4 groups were good, and no neuroma and obvious enlargement was found. At 4 and 8 weeks after operation, the electrophysiological examination results showed that the nerve conduction velocity was significantly faster in groups A and D than in groups B and C ( P<0.05), and in group B than in group C ( P<0.05); no significant difference was found between groups A and D ( P>0.05). At 8 weeks after operation, the fluorescence microscopy observation showed a large number of CM-Dil-ADSCs passing through the distal and proximal transplants in group A, and relatively few cells passing in group B. Toluidine blue staining showed that the density of myelinated nerve fibers in groups A and D were significantly higher than those in groups B and C ( P<0.05), and in group B than in group C ( P<0.05); no significant difference was found between groups A and D ( P>0.05). Transmission electron microscope observation showed that the myelinated nerve sheath in group D was large in diameter and thickness in wall. The morphology of myelin sheath in group A was irregular and smaller than that in group D, and there was no significant difference between groups B and C. Conclusion ADSCs can survive as a seed cell in vivo, and can be differentiated into Schwann-like cells under PRP induction. It can achieve better results when combined with acellular xenogeneic nerve to repair peripheral nerve injury in rabbits.
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Affiliation(s)
- Yanna Sun
- Department of Burn Plastic Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, 121000, P.R.China
| | - Rongming Zhang
- Department of Burn Plastic Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, 121000,
| | - Xu Mao
- Department of Burn Plastic Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, 121000, P.R.China
| | - Mengshu Zhang
- Department of Burn Plastic Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou Liaoning, 121000, P.R.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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Bridging the Gap: Engineered Porcine-derived Urinary Bladder Matrix Conduits as a Novel Scaffold for Peripheral Nerve Regeneration. Ann Plast Surg 2018; 78:S328-S334. [PMID: 28328634 DOI: 10.1097/sap.0000000000001042] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE This study aims to compare engineered nerve conduits constructed from porcine-derived urinary bladder matrix (UBM) with the criterion-standard nerve autografts, for segmental loss peripheral nerve repairs. METHODS Forty-eight Sprague-Dawley rats were divided into 2 groups. All underwent a 10-mm sciatic nerve gap injury. This was repaired using either (1) reverse autograft-the 10-mm cut segment was oriented 180 degrees and used to coapt the proximal and distal stumps or (2) UBM conduit-the 10-mm nerve gap was bridged with UBM conduit. Behavior assessments such as sciatic function index and foot fault asymmetry scores were performed weekly. At 3- or 6-week time endpoints, the repaired nerves and bilateral gastrocnemius/soleus muscles were harvested from each animal. Nerves were evaluated using immunohistochemistry for motor and sensory axon staining and with diffusion tensor imaging. The net wet muscle weights were calculated to assess the degree of muscle atrophy. RESULTS The UBM group demonstrated significantly improved foot fault asymmetry scores at 2 and 4 weeks, whereas there was no difference in sciatic function index. The net muscle weights were similar between both groups. Motor axon counts proximal/inside/distal to the conduit/graft were similar between UBM conduits and reverse autografts, whereas sensory axon counts within and distal to the conduit were significantly higher than those of the autograft at 6 weeks. Sensory axonal regeneration seemed to be adherent to the inner surface of the UBM conduit, whereas it had a scattered appearance in autografts. Diffusion tensor imaging parameters between groups were similar. CONCLUSIONS Urinary bladder matrix conduits prove to be at least similar to nerve autografts for the repair of peripheral nerve injuries with a short gap. The matrix perhaps serves as a scaffold to augment sensory nerve growth. CLINICAL RELEVANCE In a clinical setting, UBM may eliminate the donor site morbidity and increased operative time associated with nerve autografting.
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Mackenzie SJ, Yi JL, Singla A, Russell TM, Osterhout DJ, Calancie B. Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam. Muscle Nerve 2017; 57:E78-E84. [PMID: 28746726 DOI: 10.1002/mus.25751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 07/12/2017] [Accepted: 07/23/2017] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Treatments for patients with cauda equina injury are limited. METHODS In this study, we first used retrograde labeling to determine the relative contributions of cauda equina motor neurons to intrinsic and extrinsic rat tail muscles. Next, we transected cauda equina ventral roots and proceeded to bridge the proximal and distal stumps with either a type I collagen scaffold coated in laminin (CL) or a collagen-laminin scaffold that was also seeded with Schwann cells (CLSC). Regeneration was assessed by way of serial retrograde labeling. RESULTS After accounting for the axonal contributions to intrinsic vs. extrinsic tail muscles, we noted a higher degree of double labeling in the CLSC group (58.0 ± 39.6%) as compared with the CL group (27.8 ± 16.0%; P = 0.02), but not the control group (33.5 ± 18.2%; P = 0.10). DISCUSSION Our findings demonstrate the feasibility of using CLSCs in cauda equina injury repair. Muscle Nerve 57: E78-E84, 2018.
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Affiliation(s)
- Samuel J Mackenzie
- Department of Neuroscience, Upstate Medical University, Syracuse, New York, USA
| | - Juneyoung L Yi
- Department of Neurosurgery, Upstate Medical University, IHP 1213, 750 East Adams Street, Syracuse, New York, 13210, USA
| | - Amit Singla
- Department of Neurosurgery, Upstate Medical University, IHP 1213, 750 East Adams Street, Syracuse, New York, 13210, USA
| | - Thomas M Russell
- Department of Cell and Developmental Biology, Upstate Medical University, Syracuse, New York, USA
| | - Donna J Osterhout
- Department of Cell and Developmental Biology, Upstate Medical University, Syracuse, New York, USA
| | - Blair Calancie
- Department of Neurosurgery, Upstate Medical University, IHP 1213, 750 East Adams Street, Syracuse, New York, 13210, USA
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Costa Serrão de Araújo G, Couto Neto B, Harley Santos Botelho R, Carpi Malta M. Clinical Evaluation After Peripheral Nerve Repair With Caprolactone Neurotube. Hand (N Y) 2017; 12:168-174. [PMID: 28344529 PMCID: PMC5349409 DOI: 10.1177/1558944716643277] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Background: Peripheral nerve injuries with substance loss are challenges to surgeons because direct suture repair may result in malfunction due to nerve suture tension. Autologous nerve grafts are alternatives for treating those lesions; however, harvesting grafts adds morbidity at donor sites. Synthetic substitutes are options to bridge the gaps in these situations. The caprolactone neurotubes are used to assist nerve regeneration, but the literature lacks studies that evaluate their results. Methods: This research was designed to clinically evaluate patients undergoing repair of peripheral nerves with that conduit. We described results of 12 case series consisting of operations with Neurolac®. All nerves severed were sensory and had small gaps (ie, less than 25 mm). Subjective and objective clinical evaluations were performed and registered. Results: Physical examination by monofilament testing and 2-point discrimination showed results rated as good or excellent. However, the patients had complaints regarding sensory changes. Conclusions: Synthetic bioabsorbable guides for nerve repair are promising. The caprolactone conduits were demonstrated to be a safe option treatment and with a simple technique. Although in our study there were some operative complications, they were in line with previous descriptions in the literature. This case series added information about the treatment prognosis, but a higher evidence level study is necessary for decision making.
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Affiliation(s)
- Gabriel Costa Serrão de Araújo
- Universidade Federal Fluminense, Niterói, Brazil,Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, Brazil,Gabriel Costa Serrão de Araújo, Hospital Universitário Antônio Pedro, Rua Marques de Paraná, 303-Centro, Niterói, Rio de Janeiro, CEP 24033-900, Brazil.
| | - Bernardo Couto Neto
- Universidade Federal Fluminense, Niterói, Brazil,Universidade do Estado do Rio de Janeiro, Brazil
| | - Renato Harley Santos Botelho
- Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, Brazil,Universidade do Estado do Rio de Janeiro, Brazil
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Pollins AC, Kim JS, Boyer RB, Thayer WP. Mass spectrometry comparison of nerve allograft decellularization processes. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2017; 28:20. [PMID: 28012154 DOI: 10.1007/s10856-016-5834-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 11/25/2016] [Indexed: 06/06/2023]
Abstract
Peripheral nerve repair using nerve grafts has been investigated for several decades using traditional techniques such as histology, immunohistochemistry, and electron microscopy. Recent advances in mass spectrometry techniques have made it possible to study the proteomes of complex tissues, including extracellular matrix rich tissues similar to peripheral nerves. The present study comparatively assessed three previously described processing methods for generating acellular nerve grafts by mass spectrometry. Acellular nerve grafts were additionally examined by F-actin staining and nuclear staining for debris clearance. Application of newer techniques allowed us to detect and highlight differences among the 3 treatments. Isolated proteins were separated by mass on polyacrylamide gels serving 2 purposes. This further illustrated that these treatments differ from one another and it allowed for selective protein extractions within specific bands/molecular weights. This approach resulted in small pools of proteins that could then be analyzed by mass spectrometry for content. In total, 543 proteins were identified, many of which corroborate previous findings for these processing methods. The remaining proteins are novel discoveries that expand the field. With this pilot study, we have proven that mass spectrometry techniques complement and add value to peripheral nerve repair studies.
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Affiliation(s)
- Alonda C Pollins
- Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Justine S Kim
- Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Richard B Boyer
- Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
| | - Wesley P Thayer
- Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
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Labroo P, Shea J, Sant H, Gale B, Agarwal J. Effect Of combining FK506 and neurotrophins on neurite branching and elongation. Muscle Nerve 2016; 55:570-581. [PMID: 27503321 DOI: 10.1002/mus.25370] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 07/28/2016] [Accepted: 08/05/2016] [Indexed: 12/21/2022]
Abstract
INTRODUCTION There is a clinical need to improve the outcomes of peripheral nerve regeneration and repair after injury. In addition to its immunosuppressive effects, FK506 (tacrolimus) has been shown to have neuroregenerative properties. To determine biologically relevant local FK506 and growth factor concentrations, we performed an in vitro bioassay using dorsal root ganglion (DRG) from chicken embryos. METHODS Neurite elongation and neurite branching were analyzed microscopically after addition of FK506, glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF), each alone and in combination. RESULTS FK506 induced modest neurite elongation (∼500-800 µm) without improving neurite branching significantly. The combination of FK506 with NGF, GDNF, or both, exerted a potentiating or competitive effect on neurite elongation (∼700-1100 µm) based on dosage and competitive effect on neurite branching (∼0.2-0.4). CONCLUSIONS These results strongly suggest that the interaction of FK506 with GDNF and NGF mediates distinct enhancement of neurite growth. Muscle Nerve 55: 570-581, 2017.
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Affiliation(s)
- Pratima Labroo
- Department of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA
| | - Jill Shea
- Department of Surgery, University of Utah, 30 N 1900 E, 3b400, Salt Lake City, Utah, 84132, USA
| | - Himanshu Sant
- Department of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA
| | - Bruce Gale
- Department of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA
| | - Jayant Agarwal
- Department of Surgery, University of Utah, 30 N 1900 E, 3b400, Salt Lake City, Utah, 84132, USA
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Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery. BIOMED RESEARCH INTERNATIONAL 2016; 2016:3856262. [PMID: 27556032 PMCID: PMC4983313 DOI: 10.1155/2016/3856262] [Citation(s) in RCA: 132] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 06/29/2016] [Indexed: 01/09/2023]
Abstract
Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration.
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Klein S, Vykoukal J, Felthaus O, Dienstknecht T, Prantl L. Collagen Type I Conduits for the Regeneration of Nerve Defects. MATERIALS 2016; 9:ma9040219. [PMID: 28773346 PMCID: PMC5502670 DOI: 10.3390/ma9040219] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 03/06/2016] [Accepted: 03/14/2016] [Indexed: 12/12/2022]
Abstract
To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve repair using a type I collagen nerve conduit. Patients were re-examined at a minimal follow-up of 14.0 months and a mean follow-up of 19.9 months. Regeneration of nerve tissue within the conduits was assessed by nerve conduction velocity (NCV), a static two-point discrimination (S2PD) test, and as disability of arm shoulder and hand (DASH) outcome measure scoring. Quality of life measures including patients’ perceived satisfaction and residual pain were evaluated using a visual analog scale (VAS). No implant-related complications were observed. Seven out of 10 patients reported being free of pain, and the mean VAS was 1.1. The mean DASH score was 17.0. The S2PD was below 6 mm in 40%, between 6 and 10 mm in another 40% and above 10 mm in 20% of the patients. Eight out of 10 patients were satisfied with the procedure and would undergo surgery again. Early treatment correlated with lower DASH score levels. The use of type I collagen in large-diameter gaps in young patients and early treatment presented superior functional outcomes.
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Affiliation(s)
- Silvan Klein
- Center for Plastic-, Hand- and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany.
| | - Jody Vykoukal
- Translational Molecular Pathology, University of Texas MD, Unit 951, 7435 Fannin Street, Houston, TX 77054, USA.
| | - Oliver Felthaus
- Center for Plastic-, Hand- and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany.
| | - Thomas Dienstknecht
- Department of Orthopaedic Trauma Surgery, University Medical Center Aachen, Pauwelsstrasse 30, Aachen 52074, Germany.
| | - Lukas Prantl
- Center for Plastic-, Hand- and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany.
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Nontubulation Repair of Peripheral Nerve Gap Using Heparin/Alginate Gel Combined with b-FGF. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2016; 4:e600. [PMID: 27104099 PMCID: PMC4801089 DOI: 10.1097/gox.0000000000000581] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2015] [Accepted: 12/02/2015] [Indexed: 10/27/2022]
Abstract
All artificial nerve grafts have a tubular structure, and they guide axonal regrowth through the tube from the proximal side toward the peripheral side. Based on the results of our experimental study using animals, we used alginate gel without a tubular structure as an artificial nerve graft for digital nerve repair and evaluated peripheral nerve regeneration. In 2 patients, a gap due to digital nerve injury was bridged with controlled-release heparin/alginate gel combined with basic fibroblast growth factor, and restoration of the sensory function was serially evaluated. In both patients, Tinel's sign appeared 3-4 weeks after the operation, and sensory recovery to the fingertip was achieved at 6 months postoperatively. Our results suggest that even gel without a tubular structure provides a site for peripheral nerve regeneration.
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30
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Cheng XL, Wang P, Sun B, Liu SB, Gao YF, He XZ, Yu CY. The longitudinal epineural incision and complete nerve transection method for modeling sciatic nerve injury. Neural Regen Res 2015; 10:1663-8. [PMID: 26692866 PMCID: PMC4660762 DOI: 10.4103/1673-5374.167767] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery.
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Affiliation(s)
- Xing-Long Cheng
- Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
| | - Pei Wang
- Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
| | - Bo Sun
- Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
| | - Shi-Bo Liu
- Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
| | - Yun-Feng Gao
- Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
| | - Xin-Ze He
- Graduate School of Chengde Medical University, Chengde, Hebei Province, China
| | - Chang-Yu Yu
- Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
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Siebert JR, Eade AM, Osterhout DJ. Biomaterial Approaches to Enhancing Neurorestoration after Spinal Cord Injury: Strategies for Overcoming Inherent Biological Obstacles. BIOMED RESEARCH INTERNATIONAL 2015; 2015:752572. [PMID: 26491685 PMCID: PMC4600545 DOI: 10.1155/2015/752572] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 07/22/2015] [Indexed: 01/14/2023]
Abstract
While advances in technology and medicine have improved both longevity and quality of life in patients living with a spinal cord injury, restoration of full motor function is not often achieved. This is due to the failure of repair and regeneration of neuronal connections in the spinal cord after injury. In this review, the complicated nature of spinal cord injury is described, noting the numerous cellular and molecular events that occur in the central nervous system following a traumatic lesion. In short, postinjury tissue changes create a complex and dynamic environment that is highly inhibitory to the process of neural regeneration. Strategies for repair are outlined with a particular focus on the important role of biomaterials in designing a therapeutic treatment that can overcome this inhibitory environment. The importance of considering the inherent biological response of the central nervous system to both injury and subsequent therapeutic interventions is highlighted as a key consideration for all attempts at improving functional recovery.
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Affiliation(s)
- Justin R. Siebert
- Lake Erie College of Osteopathic Medicine at Seton Hill, Greensburg, PA 15601, USA
| | - Amber M. Eade
- Lake Erie College of Osteopathic Medicine at Seton Hill, Greensburg, PA 15601, USA
| | - Donna J. Osterhout
- Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA
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Mu Y, Wu F, Lu Y, Wei L, Yuan W. Progress of electrospun fibers as nerve conduits for neural tissue repair. Nanomedicine (Lond) 2015; 9:1869-83. [PMID: 25325242 DOI: 10.2217/nnm.14.70] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Nerve tissue regeneration approaches have gained much attention in recent years, and nerve conduits (NCs), which facilitate nerve tissue regeneration, have become an attractive alternative to nerve autologous graft. Several methods are proposed to fabricate NCs, including electrospinning, which is a widely used approach for NCs and other tissue scaffolds, and has advantages such as the ability to control the thickness, diameter and porosity of fibers, as well as its simple experimental set up. This article gives an overview of electrospun fibers for nerve conduits utilized in peripheral and central nerve regeneration. Natural and synthetic materials with different mechanical strength, degradation rates and biocompatibility are proposed. Several bioactive proteins that can help the process of nerve regeneration are introduced. Finally, some approaches to control the morphology of electrospun fibers and to deliver bioactive proteins are discussed in detail.
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Affiliation(s)
- Ying Mu
- School of Pharmacy, Shanghai JiaoTong University, Shanghai 200240, PR China
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Zhou SH, Zhen P, Li SS, Liang XY, Gao MX, Tian Q, Li XS. Allograft pretreatment for the repair of sciatic nerve defects: green tea polyphenols versus radiation. Neural Regen Res 2015; 10:136-40. [PMID: 25788934 PMCID: PMC4357097 DOI: 10.4103/1673-5374.150722] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/10/2014] [Indexed: 11/06/2022] Open
Abstract
Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can eliminate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups: autograft, fresh nerve allograft, green tea polyphenol-pretreated (1 mg/mL, 4°C) nerve allograft, and irradiation-pretreated nerve allograft (26.39 Gy/min for 12 hours; total 19 kGy). The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pretreated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the allografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to transplanting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.
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Affiliation(s)
- Sheng-Hu Zhou
- Orthopedics Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou, Gansu Province, China
| | - Ping Zhen
- Orthopedics Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou, Gansu Province, China
| | - Shen-Song Li
- Orthopedics Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou, Gansu Province, China
| | - Xiao-Yan Liang
- Orthopedics Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou, Gansu Province, China
| | - Ming-Xuan Gao
- Orthopedics Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou, Gansu Province, China
| | - Qi Tian
- Orthopedics Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou, Gansu Province, China
| | - Xu-Sheng Li
- Orthopedics Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou, Gansu Province, China
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34
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Stoppel WL, Ghezzi CE, McNamara SL, Black LD, Kaplan DL. Clinical applications of naturally derived biopolymer-based scaffolds for regenerative medicine. Ann Biomed Eng 2015; 43:657-80. [PMID: 25537688 PMCID: PMC8196399 DOI: 10.1007/s10439-014-1206-2] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 11/26/2014] [Indexed: 01/05/2023]
Abstract
Naturally derived polymeric biomaterials, such as collagens, silks, elastins, alginates, and fibrins are utilized in tissue engineering due to their biocompatibility, bioactivity, and tunable mechanical and degradation kinetics. The use of these natural biopolymers in biomedical applications is advantageous because they do not release cytotoxic degradation products, are often processed using environmentally-friendly aqueous-based methods, and their degradation rates within biological systems can be manipulated by modifying the starting formulation or processing conditions. For these reasons, many recent in vivo investigations and FDA-approval of new biomaterials for clinical use have utilized natural biopolymers as matrices for cell delivery and as scaffolds for cell-free support of native tissues. This review highlights biopolymer-based scaffolds used in clinical applications for the regeneration and repair of native tissues, with a focus on bone, skeletal muscle, peripheral nerve, cardiac muscle, and cornea substitutes.
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Affiliation(s)
- Whitney L. Stoppel
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Chiara E. Ghezzi
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Stephanie L. McNamara
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
- Cellular, Molecular and Developmental Biology Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA
- The Harvard/MIT MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA
| | - Lauren D. Black
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
- Cellular, Molecular and Developmental Biology Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA
| | - David L. Kaplan
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
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35
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Fleming ME, Bharmal H, Valerio I. Regenerative medicine applications in combat casualty care. Regen Med 2015; 9:179-90. [PMID: 24750059 DOI: 10.2217/rme.13.96] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The purpose of this report is to describe regenerative medicine applications in the management of complex injuries sustained by service members injured in support of the wars in Afghanistan and Iraq. Improvements in body armor, resuscitative techniques and faster transport have translated into increased patient survivability and more complex wounds. Combat-related blast injuries have resulted in multiple extremity injuries, significant tissue loss and amputations. Due to the limited availability and morbidity associated with autologous tissue donor sites, the introduction of regenerative medicine has been critical in managing war extremity injuries with composite massive tissue loss. Through case reports and clinical images, this report reviews the application of regenerative medicine modalities employed to manage combat-related injuries. It illustrates that the novel use of hybrid reconstructions combining traditional and regenerative medicine approaches are an effective tool in managing wounds. Lessons learned can be adapted to civilian care.
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Affiliation(s)
- Mark E Fleming
- Department of Orthopaedics, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20889, USA
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36
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Zack-Williams SDL, Butler PE, Kalaskar DM. Current progress in use of adipose derived stem cells in peripheral nerve regeneration. World J Stem Cells 2015; 7:51-64. [PMID: 25621105 PMCID: PMC4300936 DOI: 10.4252/wjsc.v7.i1.51] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 09/25/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair.
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37
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de Luca AC, Lacour SP, Raffoul W, di Summa PG. Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration? Neural Regen Res 2015; 9:1943-8. [PMID: 25598773 PMCID: PMC4283273 DOI: 10.4103/1673-5374.145366] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2014] [Indexed: 01/09/2023] Open
Abstract
Peripheral nerve injury is a serious problem affecting significantly patients’ life. Autografts are the “gold standard” used to repair the injury gap, however, only 50% of patients fully recover from the trauma. Artificial conduits are a valid alternative to repairing peripheral nerve. They aim at confining the nerve environment throughout the regeneration process, and providing guidance to axon outgrowth. Biocompatible materials have been carefully designed to reduce inflammation and scar tissue formation, but modifications of the inner lumen are still required in order to optimise the scaffolds. Biomicking the native neural tissue with extracellular matrix fillers or coatings showed great promises in repairing longer gaps and extending cell survival. In addition, extracellular matrix molecules provide a platform to further bind growth factors that can be released in the system over time. Alternatively, conduit fillers can be used for cell transplantation at the injury site, reducing the lag time required for endogenous Schwann cells to proliferate and take part in the regeneration process. This review provides an overview on the importance of extracellular matrix molecules in peripheral nerve repair.
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Affiliation(s)
- Alba C de Luca
- EPFL, Centre for Neuroprosthetics, Laboratory for Soft Bioelectronic Interfaces, Station 17, 1015 Lausanne, Switzerland
| | - Stephanie P Lacour
- EPFL, Centre for Neuroprosthetics, Laboratory for Soft Bioelectronic Interfaces, Station 17, 1015 Lausanne, Switzerland
| | - Wassim Raffoul
- Department of Plastic, Reconstructive and Hand Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - Pietro G di Summa
- Department of Plastic, Reconstructive and Hand Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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38
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Cwykiel J, Tfaily EB, Siemionow MZ. Cellular Therapies in Nerve Regeneration. Plast Reconstr Surg 2015. [DOI: 10.1007/978-1-4471-6335-0_76] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Chen X, Yin Y, Zhang T, Zhao Y, Yang Y, Yu X, Wang H. Ultrasound imaging of chitosan nerve conduits that bridge sciatic nerve defects in rats. Neural Regen Res 2014; 9:1386-8. [PMID: 25221596 PMCID: PMC4160870 DOI: 10.4103/1673-5374.137592] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/06/2014] [Indexed: 12/02/2022] Open
Affiliation(s)
- Xiaoyang Chen
- Department of Doppler Ultrasound, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Yifei Yin
- Department of Doppler Ultrasound, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Tingting Zhang
- Department of Doppler Ultrasound, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Yahong Zhao
- Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
| | - Yumin Yang
- Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
| | - Xiaomei Yu
- Department of Doppler Ultrasound, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Hongkui Wang
- School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China ; Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
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Abstract
Management of brachial plexus injury is a demanding field of hand and upper extremity surgery. With currently available microsurgical techniques, functional gains are rewarding in upper plexus injuries. However, treatment options in the management of flail and anaesthetic limb are still evolving. Last three decades have witnessed significant developments in the management of these injuries, which include a better understanding of the anatomy, advances in the diagnostic modalities, incorporation of intra-operative nerve stimulation techniques, more liberal use of nerve grafts in bridging nerve gaps, and the addition of new nerve transfers, which selectively neurotise the target muscles close to the motor end plates. Newer research works on the use of nerve allografts and immune modulators (FK 506) are under evaluation in further improving the results in nerve reconstruction. Direct reimplantation of avulsed spinal nerve roots into the spinal cord is another area of research in brachial plexus reconstruction.
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Affiliation(s)
- Prem Singh Bhandari
- Department of Plastic Surgery, Command Hospital (NC), Panchkula, Haryana, India
| | - Sanjay Maurya
- Command Hospital (WC), Chandimandir Cantt, Panchkula, Haryana, India
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Grahn PJ, Vaishya S, Knight A, Chen BK, Schmeichel A, Currier B, Spinner R, Yaszemski M, Windebank A. Implantation of cauda equina nerve roots through a biodegradable scaffold at the conus medullaris in rat. Spine J 2014; 14:2172-7. [PMID: 24509005 PMCID: PMC4125550 DOI: 10.1016/j.spinee.2014.01.059] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Revised: 12/17/2013] [Accepted: 01/29/2014] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Traumatic injuries occurring at the conus medullaris of the spinal cord cause permanent damage both to the central nervous system and to the cauda equina nerve roots. PURPOSE This proof-of-concept study was to determine whether implanting the nerve roots into a biodegradable scaffold would improve regeneration after injury. METHODS All experimental works involving rats were performed according to the approved guidelines by the Mayo Clinic Institutional Animal Care and Use Committee. Surgical procedures were performed on 32 Sprague-Dawley rats. Four ventral cauda equina nerve roots were reimplanted either directly into the ventral cord stump or through a poly(lactic-co-glycolic acid) (PLGA) scaffold. These experimental groups were compared with a control group in which the nerves were inserted into a muscle fascia barrier that was placed between the spinal cord and the nerve roots. Animals were sacrificed at 4 weeks. RESULTS There was no difference in motor neuron counts in the spinal cord rostral to the injury in all treatment groups, implying equal potential for the regeneration into implanted nerve roots. One-way analysis of variance testing, with Tukey post hoc test, showed a statistically significant improvement in axon regeneration through the injury in the PLGA scaffold treatment group compared with the control (p<.05, scaffold n=11, control n=11). CONCLUSIONS This pilot study demonstrated that a PLGA scaffold improved regeneration of axons into peripheral nerve roots. However, the number of regenerating axons observed was limited and did not lead to functional recovery. Future experiments will employ a different scaffold material and possible growth factors or enzymes to increase axon populations.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Anthony Windebank
- Mayo Graduate School, Mayo Clinic,Department of Neurology, Mayo Clinic
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Abstract
Autologous nerve grafts are the current criterion standard for repair of peripheral nerve injuries when the transected nerve ends are not amenable to primary end-to-end tensionless neurorrhaphy. However, donor-site morbidities such as neuroma formation and permanent loss of function have led to tremendous interest in developing an alternative to this technique. Artificial nerve conduits have therefore emerged as an alternative to autologous nerve grafting for the repair of short peripheral nerve defects of less than 30 mm; however, they do not yet surpass autologous nerve grafts clinically. A thorough understanding of the complex biological reactions that take place during peripheral nerve regeneration will allow researchers to develop a nerve conduit with physical and biological properties similar to those of an autologous nerve graft that supports regeneration over long nerve gaps and in large-diameter nerves. In this article, the authors assess the currently available nerve conduits, summarize research in the field of developing these conduits, and establish areas within this field in which further research would prove most beneficial.
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Cirillo V, Clements BA, Guarino V, Bushman J, Kohn J, Ambrosio L. A comparison of the performance of mono- and bi-component electrospun conduits in a rat sciatic model. Biomaterials 2014; 35:8970-82. [PMID: 25085857 DOI: 10.1016/j.biomaterials.2014.07.010] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Accepted: 07/10/2014] [Indexed: 12/16/2022]
Abstract
Synthetic nerve conduits represent a promising strategy to enhance functional recovery in peripheral nerve injury repair. However, the efficiency of synthetic nerve conduits is often compromised by the lack of molecular factors to create an enriched microenvironment for nerve regeneration. Here, we investigate the in vivo response of mono (MC) and bi-component (BC) fibrous conduits obtained by processing via electrospinning poly(ε-caprolactone) (PCL) and gelatin solutions. In vitro studies demonstrate that the inclusion of gelatin leads to uniform electrospun fiber size and positively influences the response of Dorsal Root Ganglia (DRGs) neurons as confirmed by the preferential extensions of neurites from DRG bodies. This behavior can be attributed to gelatin as a bioactive cue for the cultured DRG and to the reduced fibers size. However, in vivo studies in rat sciatic nerve defect model show an opposite response: MC conduits stimulate superior nerve regeneration than gelatin containing PCL conduits as confirmed by electrophysiology, muscle weight and histology. The G-ratio, 0.71 ± 0.07 for MC and 0.66 ± 0.05 for autograft, is close to 0.6, the value measured in healthy nerves. In contrast, BC implants elicited a strong host response and infiltrating tissue occluded the conduits preventing the formation of myelinated axons. Therefore, although gelatin promotes in vitro nerve regeneration, we conclude that bi-component electrospun conduits are not satisfactory in vivo due to intrinsic limits to their mechanical performance and degradation kinetics, which are essential to peripheral nerve regeneration in vivo.
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Affiliation(s)
- Valentina Cirillo
- Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale Kennedy 54, Naples 80125, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Naples Federico II, P.leTecchio 80, Naples 80125, Italy
| | - Basak A Clements
- New Jersey Center for Biomaterials, Rutgers - The State University of NJ, 145 Bevier Road, Piscataway, NJ 08854, USA
| | - Vincenzo Guarino
- Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale Kennedy 54, Naples 80125, Italy.
| | - Jared Bushman
- New Jersey Center for Biomaterials, Rutgers - The State University of NJ, 145 Bevier Road, Piscataway, NJ 08854, USA
| | - Joachim Kohn
- New Jersey Center for Biomaterials, Rutgers - The State University of NJ, 145 Bevier Road, Piscataway, NJ 08854, USA
| | - Luigi Ambrosio
- Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale Kennedy 54, Naples 80125, Italy
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Barton MJ, Morley JW, Stoodley MA, Lauto A, Mahns DA. Nerve repair: toward a sutureless approach. Neurosurg Rev 2014; 37:585-95. [PMID: 25015388 DOI: 10.1007/s10143-014-0559-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Revised: 02/04/2014] [Accepted: 04/13/2014] [Indexed: 12/16/2022]
Abstract
Peripheral nerve repair for complete section injuries employ reconstructive techniques that invariably require sutures in their application. Sutures are unable to seal the nerve, thus incapable of preventing leakage of important intraneural fluids from the regenerating nerve. Furthermore, sutures are technically demanding to apply for direct repairs and often induce detrimental scarring that impedes healing and functional recovery. To overcome these limitations, biocompatible and biodegradable glues have been used to seal and repair peripheral nerves. Although creating a sufficient seal, they can lack flexibility and present infection risks or cytotoxicity. Other adhesive biomaterials have recently emerged into practice that are usually based on proteins such as albumin and collagen or polysaccharides like chitosan. These adhesives form their union to nerve tissue by either photothermal (tissue welding) or photochemical (tissue bonding) activation with laser light. These biomaterial adhesives offer significant advantages over sutures, such as their capacity to unite and seal the epineurium, ease of application, reduced invasiveness and add the potential for drug delivery in situ to facilitate regeneration. This paper reviews a number of different peripheral nerve repair (or reconstructive) techniques currently used clinically and in experimental procedures for nerve injuries with or without tissue deficit.
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Affiliation(s)
- Matthew J Barton
- Griffith Health Institute, Griffith University, Gold Coast Campus, Queensland, 4222, Australia,
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45
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Nelson MR, Armenta AH. Birth Brachial Plexus Palsy Update. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2014. [DOI: 10.1007/s40141-014-0048-z] [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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46
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Abstract
Nerve conduits and acellular nerve allograft offer efficient and convenient tools for overcoming unexpected gaps during nerve repair. Both techniques offer guidance for migrating Schwann cells and axonal regeneration though utilizing very different scaffolds. The substantially greater amount of animal and clinical data published on nerve conduits is marked by wide discrepancies in results that may be partly explained by a still poorly defined critical repair gap and diameter size. The available information on acellular allografts appears more consistently positive though this tool is also hampered by a longer but also limited critical length. This article reviews the current relative literature and examines pertinent parameters for application of both acellular allograft and nerve conduits in overcoming short nerve gaps.
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47
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di Summa PG, Kingham PJ, Campisi CC, Raffoul W, Kalbermatten DF. Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair. Neurosci Lett 2014; 572:26-31. [PMID: 24792394 DOI: 10.1016/j.neulet.2014.04.029] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 04/07/2014] [Accepted: 04/17/2014] [Indexed: 02/08/2023]
Abstract
Collagen nerve guides are used clinically for peripheral nerve defects, but their use is generally limited to lesions up to 3 cm. In this study we combined collagen conduits with cells as an alternative strategy to support nerve regeneration over longer gaps. In vitro cell adherence to collagen conduits (NeuraGen(®) nerve guides) was assessed by scanning electron microscopy. For in vivo experiments, conduits were seeded with either Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC) or left empty (control group), conduits were used to bridge a 1cm gap in the rat sciatic nerve and after 2-weeks immunohistochemical analysis was performed to assess axonal regeneration and SC infiltration. The regenerative cells showed good adherence to the collagen walls. Primary SC showed significant improvement in distal stump sprouting. No significant differences in proximal regeneration distances were noticed among experimental groups. dMSC and dASC-loaded conduits showed a diffuse sprouting pattern, while SC-loaded showed an enhanced cone pattern and a typical sprouting along the conduits walls, suggesting an increased affinity for the collagen type I fibrillar structure. NeuraGen(®) guides showed high affinity of regenerative cells and could be used as efficient vehicle for cell delivery. However, surface modifications (e.g. with extracellular matrix molecule peptides) of NeuraGen(®) guides could be used in future tissue-engineering applications to better exploit the cell potential.
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Affiliation(s)
- Pietro G di Summa
- Department of Plastic, Reconstructive Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland.
| | - Paul J Kingham
- Section for Anatomy, Department of Integrative Medical Biology, Umeå universitet, hus H, Biologihuset, SE-901 87 Umeå, Sweden.
| | - Corrado C Campisi
- Department of Plastic, Reconstructive Surgery, University Hospital of Genova, Ospedale S. Martino, Largo Rossana Benzi 10, 16132 Genova, Italy.
| | - Wassim Raffoul
- Department of Plastic, Reconstructive Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland.
| | - Daniel F Kalbermatten
- Department of Plastic, Reconstructive Surgery, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland.
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48
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Semere A, Morand B, Loury J, Vuillerme N, Bettega G. [Repair of a facial nerve substance loss by interposition of a collagen neurotube]. ANN CHIR PLAST ESTH 2014; 59:273-5. [PMID: 24698336 DOI: 10.1016/j.anplas.2014.03.001] [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: 01/06/2014] [Accepted: 03/02/2014] [Indexed: 10/25/2022]
Abstract
We are exposing the case of a 22 year-old patient presenting a wound of the right cheek, with a palsy of the right corner of the mouth. He has been sent to us 6 days after the trauma for secondary exploration. A section of the buccal branch of the right facial nerve with a 1cm gap has been brought out. We have bypassed the loss of substance with a collagen absorbable biological conduit. The 6-months clinical and electromyographic follow-up has shown a clear improvement of the function of the orbicularis oris, as well as its reinnervation by the buccal branch of the right facial nerve.
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Affiliation(s)
- A Semere
- Service de chirurgie de la main et des brûlés, hôpital Michallon, BP 217, 38043 Grenoble cedex 9, France.
| | - B Morand
- Service de chirurgie plastique maxillo-faciale, hôpital Michallon, BP 217, 38043 Grenoble cedex 9, France
| | - J Loury
- Clinique des Cèdres, 21, rue Albert-Londres, 38432 Echirolles, France
| | - N Vuillerme
- Laboratoire AGIM (AGeing Imaging, Modeling) Lab, faculté de médecine, Bât-Jean-Roget, 38706 La Tronche cedex, France
| | - G Bettega
- Service de chirurgie plastique maxillo-faciale, hôpital Michallon, BP 217, 38043 Grenoble cedex 9, France
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49
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Pace LA, Plate JF, Mannava S, Barnwell JC, Koman LA, Li Z, Smith TL, Van Dyke M. A human hair keratin hydrogel scaffold enhances median nerve regeneration in nonhuman primates: an electrophysiological and histological study. Tissue Eng Part A 2013; 20:507-17. [PMID: 24083825 DOI: 10.1089/ten.tea.2013.0084] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
A human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve conduit luminal filler following median nerve transection injury in 10 Macaca fascicularis nonhuman primates (NHP). A 1 cm nerve gap was grafted with a NeuraGen® collagen conduit filled with either saline or keratin hydrogel and nerve regeneration was evaluated by electrophysiology for a period of 12 months. The keratin hydrogel-grafted nerves showed significant improvement in return of compound motor action potential (CMAP) latency and recovery of baseline nerve conduction velocity (NCV) compared with the saline-treated nerves. Histological evaluation was performed on retrieved median nerves and abductor pollicis brevis (APB) muscles at 12 months. Nerve histomorphometry showed a significantly larger nerve area in the keratin group compared with the saline group and the keratin APB muscles had a significantly higher myofiber density than the saline group. This is the first published study to show that an acellular biomaterial hydrogel conduit filler can be used to enhance peripheral nerve regeneration and motor recovery in an NHP model.
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Affiliation(s)
- Lauren A Pace
- 1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine , Winston-Salem, North Carolina
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50
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Pace LA, Plate JF, Smith TL, Van Dyke ME. The effect of human hair keratin hydrogel on early cellular response to sciatic nerve injury in a rat model. Biomaterials 2013; 34:5907-14. [DOI: 10.1016/j.biomaterials.2013.04.024] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Accepted: 04/10/2013] [Indexed: 01/09/2023]
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