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de Araújo RS, Mussalem MGVB, Carrijo GS, Bani JVDF, Ferreira LM. Adipose Tissue Derivatives in Peripheral Nerve Regeneration after Transection: A Systematic Review. Bioengineering (Basel) 2024; 11:697. [PMID: 39061779 PMCID: PMC11274242 DOI: 10.3390/bioengineering11070697] [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: 04/26/2024] [Revised: 06/08/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
INTRODUCTION Peripheral nerve injury (PNI) is increasingly prevalent and challenging to treat despite advances in microsurgical techniques. In this context, adipose tissue derivatives, such as adipose-derived stem cells, nanofat, and stromal vascular fraction have been gaining attention as potential allies in peripheral nerve regeneration. OBJECTIVES This study aims to explore the use of adipose tissue derivatives in nerve regeneration following peripheral nerve transection in murine models. Thus, we assess and synthesize the key techniques and methods used for evaluating the obtained nerve regeneration to guide future experimental research and clinical interventions. METHODOLOGY A systematic review was conducted in February 2024, adhering to the Cochrane and PRISMA 2020 guidelines, using the PubMed, SciELO, and LILACS databases. The focus was on experimental studies involving adipose tissue derivatives in nerve regeneration in animal models post-transection. Only experimental trials reporting nerve regeneration outcomes were included; studies lacking a comparator group or evaluation methods were excluded. RESULTS Out of 273 studies initially identified from MEDLINE, 19 were selected for detailed analysis. The average study included 32.5 subjects, with about 10.2 subjects per intervention subgroup. The predominant model was the sciatic nerve injury with a 10 mm gap. The most common intervention involved unprocessed adipose-derived stem cells, utilized in 14 articles. CONCLUSIONS This review underscores the significant potential of current methodologies in peripheral nerve regeneration, particularly highlighting the use of murine models and thorough evaluation techniques.
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Affiliation(s)
- Rafael Silva de Araújo
- Federal University of São Paulo, Department of Plastic Surgery, São Paulo 04038-001, Brazil; (M.G.V.B.M.); (J.V.d.F.B.); (L.M.F.)
| | | | | | - João Victor de Figueiredo Bani
- Federal University of São Paulo, Department of Plastic Surgery, São Paulo 04038-001, Brazil; (M.G.V.B.M.); (J.V.d.F.B.); (L.M.F.)
| | - Lydia Masako Ferreira
- Federal University of São Paulo, Department of Plastic Surgery, São Paulo 04038-001, Brazil; (M.G.V.B.M.); (J.V.d.F.B.); (L.M.F.)
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da Silva MDV, Piva M, Martelossi-Cebinelli G, Stinglin Rosa Ribas M, Hoffmann Salles Bianchini B, K Heintz O, Casagrande R, Verri WA. Stem cells and pain. World J Stem Cells 2023; 15:1035-1062. [PMID: 38179216 PMCID: PMC10762525 DOI: 10.4252/wjsc.v15.i12.1035] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 11/06/2023] [Accepted: 11/30/2023] [Indexed: 12/26/2023] Open
Abstract
Pain can be defined as an unpleasant sensory and emotional experience caused by either actual or potential tissue damage or even resemble that unpleasant experience. For years, science has sought to find treatment alternatives, with minimal side effects, to relieve pain. However, the currently available pharmacological options on the market show significant adverse events. Therefore, the search for a safer and highly efficient analgesic treatment has become a priority. Stem cells (SCs) are non-specialized cells with a high capacity for replication, self-renewal, and a wide range of differentiation possibilities. In this review, we provide evidence that the immune and neuromodulatory properties of SCs can be a valuable tool in the search for ideal treatment strategies for different types of pain. With the advantage of multiple administration routes and dosages, therapies based on SCs for pain relief have demonstrated meaningful results with few downsides. Nonetheless, there are still more questions than answers when it comes to the mechanisms and pathways of pain targeted by SCs. Thus, this is an evolving field that merits further investigation towards the development of SC-based analgesic therapies, and this review will approach all of these aspects.
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Affiliation(s)
- Matheus Deroco Veloso da Silva
- Department of Pathology, Laboratory of Pain, Inflammation, Neuropathy and Cancer, State University of Londrina, Londrina 86057-970, Paraná, Brazil
| | - Maiara Piva
- Department of Pathology, Laboratory of Pain, Inflammation, Neuropathy and Cancer, State University of Londrina, Londrina 86057-970, Paraná, Brazil
| | - Geovana Martelossi-Cebinelli
- Department of Pathology, Laboratory of Pain, Inflammation, Neuropathy and Cancer, State University of Londrina, Londrina 86057-970, Paraná, Brazil
| | - Mariana Stinglin Rosa Ribas
- Department of Pathology, Laboratory of Pain, Inflammation, Neuropathy and Cancer, State University of Londrina, Londrina 86057-970, Paraná, Brazil
| | - Beatriz Hoffmann Salles Bianchini
- Department of Pathology, Laboratory of Pain, Inflammation, Neuropathy and Cancer, State University of Londrina, Londrina 86057-970, Paraná, Brazil
| | - Olivia K Heintz
- Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States
| | - Rubia Casagrande
- Department of Pharmaceutical Sciences, Center of Health Science, State University of Londrina, Londrina 86038-440, Paraná, Brazil
| | - Waldiceu A Verri
- Department of Pathology, Laboratory of Pain, Inflammation, Neuropathy and Cancer, Center of Biological Sciences, State University of Londrina, Londrina 86057-970, Paraná, Brazil.
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Hasiba-Pappas S, Kamolz LP, Luze H, Nischwitz SP, Lumenta DB, Winter R. Regenerative Therapies for Basal Thumb Arthritis-A Systematic Review. Int J Mol Sci 2023; 24:14909. [PMID: 37834357 PMCID: PMC10573355 DOI: 10.3390/ijms241914909] [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: 09/18/2023] [Revised: 10/02/2023] [Accepted: 10/03/2023] [Indexed: 10/15/2023] Open
Abstract
Basal thumb arthritis is a painful and debilitating pathology that can severely reduce a patients' quality of life. Common therapies include oral pain control, local steroid injections and/or surgery. Yet, therapeutic data on long-term improvement and even cartilage repair are scarce. This review aims to present the currently available literature on novel therapies for basal thumb arthritis, including platelet-rich plasma (PRP), fat grafting and phototherapy, and investigate their potential efficacy. The entire OVID database and PubMed were searched for studies containing the topics PRP injection, lipofilling, laser treatment and regenerative treatment for carpometacarpal arthritis. Seven studies on the effect of fat tissue on basal thumb arthritis were found. Four authors reported on PRP injections, one RCT examined a combinational treatment of PRP and fat grafting, another phototherapy for the thumb joint and one prospective trial on chondrocyte transplantation was found. Pain improvement and decreased impairment were reported in the majority of PRP and/or fat grafting studies as well as after chondrocyte implantation. Phototherapy did not significantly improve the condition. This review revealed that only limited data on regenerative therapies for carpometacarpal arthritis are currently available, yet PRP and lipofilling show promising results and merit further investigation.
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Affiliation(s)
- Sophie Hasiba-Pappas
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria; (S.H.-P.); (L.-P.K.); (D.B.L.)
| | - Lars-P. Kamolz
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria; (S.H.-P.); (L.-P.K.); (D.B.L.)
- COREMED—Cooperative Centre for Regenerative Medicine, Joanneum Research GmbH, Neue Stiftingtalstr. 2, A-8010 Graz, Austria
| | - Hanna Luze
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria; (S.H.-P.); (L.-P.K.); (D.B.L.)
| | - Sebastian P. Nischwitz
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria; (S.H.-P.); (L.-P.K.); (D.B.L.)
| | - David B. Lumenta
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria; (S.H.-P.); (L.-P.K.); (D.B.L.)
| | - Raimund Winter
- Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria; (S.H.-P.); (L.-P.K.); (D.B.L.)
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Tiwari AP, Lokai T, Albin B, Yang IH. A Review on the Technological Advances and Future Perspectives of Axon Guidance and Regeneration in Peripheral Nerve Repair. Bioengineering (Basel) 2022; 9:bioengineering9100562. [PMID: 36290530 PMCID: PMC9598559 DOI: 10.3390/bioengineering9100562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 10/03/2022] [Accepted: 10/11/2022] [Indexed: 11/16/2022] Open
Abstract
Despite a significant advance in the pathophysiological understanding of peripheral nerve damage, the successful treatment of large nerve defects remains an unmet medical need. In this article, axon growth guidance for peripheral nerve regeneration was systematically reviewed and discussed mainly from the engineering perspective. In addition, the common approaches to surgery, bioengineering approaches to emerging technologies such as optogenetic stimulation and magnetic stimulation for functional recovery were discussed, along with their pros and cons. Additionally, clear future perspectives of axon guidance and nerve regeneration were addressed.
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Gao X, Du P, Xu J, Sun J, Ding W, Yang DL. Repair of cerebrospinal fluid leak during posterior thoracolumbar surgery using paraspinal muscle flap combined with fat graft. Front Surg 2022; 9:969954. [PMID: 36299572 PMCID: PMC9589508 DOI: 10.3389/fsurg.2022.969954] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 09/20/2022] [Indexed: 11/05/2022] Open
Abstract
Objective This study aimed to propose a novel surgical method via combination of fat graft and paraspinal muscle flap, in order to treat cerebrospinal fluid (CSF) leak during posterior thoracolumbar surgery. The clinical outcomes were also evaluated. Methods Data of a total of 71 patients who were diagnosed with intraoperative incidental durotomy and CSF leak after posterior thoracolumbar surgery in our hospital form January 2019 to January 2021 were retrospectively collected and analyzed. Among them, 34 and 37 patients were assigned into conventional suturing (CS) group and fat graft and paraspinal muscle flap (FPM) group, respectively. Patients’ demographic and clinical data were compared between the two groups. Results The average drainage tube time in the FPM group was 3.89 ± 1.17 days, which was shorter than that in the CS group (5.12 ± 1.56, P < 0.001). The drainage volume in the FPM group (281.08 ± 284.76 ml) was also smaller than that in the CS group (859.70 ± 553.11 ml, P < 0.001). Besides, 15 (44.11%) patients in the CS group complained of postural headache, which was more than that in the FPM group (7 patients, 18.91%). There was a statistically significant difference in postoperative visual analogue scale (VAS) score between the two groups (P = 0.013). Two patients underwent revision surgery resulting from incision nonunion and delayed meningeal cyst. Conclusion Fat graft combined with paraspinal muscle flap showed to be an effective method to repair CSF leak during posterior thoracolumbar surgery. The proposed method significantly reduced postoperative drainage tube time and postoperative drainage volume. It also decreased the incidence and the degree of postural headache. The proposed method showed satisfactory clinical outcomes, and it is worthy of promotion.
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Phamornnak C, Han B, Spencer BF, Ashton MD, Blanford CF, Hardy JG, Blaker JJ, Cartmell SH. Instructive electroactive electrospun silk fibroin-based biomaterials for peripheral nerve tissue engineering. BIOMATERIALS ADVANCES 2022; 141:213094. [PMID: 36162344 DOI: 10.1016/j.bioadv.2022.213094] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 07/03/2022] [Accepted: 08/22/2022] [Indexed: 10/15/2022]
Abstract
Aligned sub-micron fibres are an outstanding surface for orienting and promoting neurite outgrowth; therefore, attractive features to include in peripheral nerve tissue scaffolds. A new generation of peripheral nerve tissue scaffolds is under development incorporating electroactive materials and electrical regimes as instructive cues in order to facilitate fully functional regeneration. Herein, electroactive fibres composed of silk fibroin (SF) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) were developed as a novel peripheral nerve tissue scaffold. Mats of SF with sub-micron fibre diameters of 190 ± 50 nm were fabricated by double layer electrospinning with thicknesses of ∼100 μm (∼70-80 μm random fibres and ∼20-30 μm aligned fibres). Electrospun SF mats were modified with interpenetrating polymer networks (IPN) of PEDOT:PSS in various ratios of PSS/EDOT (α) and the polymerisation was assessed by hard X-ray photoelectron spectroscopy (HAXPES). The mechanical properties of electrospun SF and IPNs mats were characterised in the wet state tensile and the electrical properties were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The cytotoxicity and biocompatibility of the optimal IPNs (α = 2.3 and 3.3) mats were ascertained via the growth and neurite extension of mouse neuroblastoma x rat glioma hybrid cells (NG108-15) for 7 days. The longest neurite outgrowth of 300 μm was observed in the parallel direction of fibre alignment on laminin-coated electrospun SF and IPN (α = 2.3) mats which is the material with the lowest electron transfer resistance (Ret, ca. 330 Ω). These electrically conductive composites with aligned sub-micron fibres exhibit promise for axon guidance and also have the potential to be combined with electrical stimulation treatment as a further step for the effective regeneration of nerves.
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Sumarwoto T, Suroto H, Mahyudin F, Utomo DN, Romaniyanto, Tinduh D, Notobroto HB, Sigit Prakoeswa CR, Rantam FA, Rhatomy S. Role of adipose mesenchymal stem cells and secretome in peripheral nerve regeneration. Ann Med Surg (Lond) 2021; 67:102482. [PMID: 34168873 PMCID: PMC8209190 DOI: 10.1016/j.amsu.2021.102482] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/01/2021] [Accepted: 06/05/2021] [Indexed: 01/08/2023] Open
Abstract
The use of stem cells is a breakthrough in medical biotechnology which brings regenerative therapy into a new era. Over the past several decades, stem cells had been widely used as regenerative therapy and Mesenchymal Stem Cells (MSCs) had emerged as a promising therapeutic option. Currently stem cells are effective therapeutic agents againts several diseases due to their tissue protective and repair mechanisms. This therapeutic effect is largely due to the biomolecular properties including secretomes. Injury to peripheral nerves has significant health and economic consequences, and no surgical procedure can completely restore sensory and motor function. Stem cell therapy in peripheral nerve injury is an important future intervention to achieve the best clinical outcome improvement. Adipose mesenchymal stem cells (AdMSCs) are multipotent mesenchymal stem cells which are similar to bone marrow-derived mesenchymal stem cells (BM-MSCs). The following review aims to provide an overview of the use of AdMSCs and their secretomes in regenerating peripheral nerves.
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Affiliation(s)
- Tito Sumarwoto
- Doctoral Program, Faculty of Medicine, Airlangga University, Surabaya, Indonesia.,Department of Orthopaedics and Traumatology, Prof Soeharso Orthopaedic Hospital, Sebelas Maret University, Surakarta, Indonesia.,Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
| | - Heri Suroto
- Department of Orthopaedic and Traumatology, dr. Soetomo General Hospital, Airlangga University, Surabaya, Indonesia.,Faculty of Medicine, Airlangga University, Surabaya, Indonesia
| | - Ferdiansyah Mahyudin
- Department of Orthopaedic and Traumatology, dr. Soetomo General Hospital, Airlangga University, Surabaya, Indonesia.,Faculty of Medicine, Airlangga University, Surabaya, Indonesia
| | - Dwikora Novembri Utomo
- Department of Orthopaedic and Traumatology, dr. Soetomo General Hospital, Airlangga University, Surabaya, Indonesia.,Faculty of Medicine, Airlangga University, Surabaya, Indonesia
| | - Romaniyanto
- Department of Orthopaedics and Traumatology, Prof Soeharso Orthopaedic Hospital, Sebelas Maret University, Surakarta, Indonesia.,Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
| | - Damayanti Tinduh
- Faculty of Medicine, Airlangga University, Surabaya, Indonesia.,Physical Medicine and Rehabilitation Department, Universitas Airlangga, Surabaya, Indonesia
| | | | - Cita Rosita Sigit Prakoeswa
- Department of Dermatology and Venereology, dr. Soetomo General Hospital, Airlangga University, Surabaya, Indonesia.,Faculty of Medicine, Airlangga University, Surabaya, Indonesia
| | - Fedik Abdul Rantam
- Virology and Immunology Laboratory, Microbiology Department, Faculty of Veterinary Medicine, Airlangga University, Surabaya, Indonesia.,Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia
| | - Sholahuddin Rhatomy
- Department of Orthopaedics and Traumatology, dr. Soeradji Tirtonegoro General Hospital, Klaten, Indonesia.,Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
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Leberfinger AN, Dinda S, Wu Y, Koduru SV, Ozbolat V, Ravnic DJ, Ozbolat IT. Bioprinting functional tissues. Acta Biomater 2019; 95:32-49. [PMID: 30639351 PMCID: PMC6625952 DOI: 10.1016/j.actbio.2019.01.009] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 12/31/2018] [Accepted: 01/09/2019] [Indexed: 12/23/2022]
Abstract
Despite the numerous lives that have been saved since the first successful procedure in 1954, organ transplant has several shortcomings which prevent it from becoming a more comprehensive solution for medical care than it is today. There is a considerable shortage of organ donors, leading to patient death in many cases. In addition, patients require lifelong immunosuppression to prevent graft rejection postoperatively. With such issues in mind, recent research has focused on possible solutions for the lack of access to donor organs and rejections, with the possibility of using the patient's own cells and tissues for treatment showing enormous potential. Three-dimensional (3D) bioprinting is a rapidly emerging technology, which holds great promise for fabrication of functional tissues and organs. Bioprinting offers the means of utilizing a patient's cells to design and fabricate constructs for replacement of diseased tissues and organs. It enables the precise positioning of cells and biologics in an automated and high throughput manner. Several studies have shown the promise of 3D bioprinting. However, many problems must be overcome before the generation of functional tissues with biologically-relevant scale is possible. Specific focus on the functionality of bioprinted tissues is required prior to clinical translation. In this perspective, this paper discusses the challenges of functionalization of bioprinted tissue under eight dimensions: biomimicry, cell density, vascularization, innervation, heterogeneity, engraftment, mechanics, and tissue-specific function, and strives to inform the reader with directions in bioprinting complex and volumetric tissues. STATEMENT OF SIGNIFICANCE: With thousands of patients dying each year waiting for an organ transplant, bioprinted tissues and organs show the potential to eliminate this ever-increasing organ shortage crisis. However, this potential can only be realized by better understanding the functionality of the organ and developing the ability to translate this to the bioprinting methodologies. Considering the rate at which the field is currently expanding, it is reasonable to expect bioprinting to become an integral component of regenerative medicine. For this purpose, this paper discusses several factors that are critical for printing functional tissues including cell density, vascularization, innervation, heterogeneity, engraftment, mechanics, and tissue-specific function, and inform the reader with future directions in bioprinting complex and volumetric tissues.
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Affiliation(s)
- Ashley N Leberfinger
- Department of Surgery, Penn State University College of Medicine, Hershey, PA 17033, USA
| | - Shantanab Dinda
- Department of Industrial and Manufacturing Engineering, The Pennsylvania State University, University Park, PA 16802, USA; The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
| | - Yang Wu
- The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA; Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802, USA
| | - Srinivas V Koduru
- Department of Surgery, Penn State University College of Medicine, Hershey, PA 17033, USA
| | - Veli Ozbolat
- The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA; Ceyhan Engineering Faculty, Cukurova University, Ceyhan, Adana 01950, Turkey
| | - Dino J Ravnic
- Department of Surgery, Penn State University College of Medicine, Hershey, PA 17033, USA
| | - Ibrahim T Ozbolat
- The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA; Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802, USA; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
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Mobini S, Spearman BS, Lacko CS, Schmidt CE. Recent advances in strategies for peripheral nerve tissue engineering. CURRENT OPINION IN BIOMEDICAL ENGINEERING 2017. [DOI: 10.1016/j.cobme.2017.10.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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