Biomaterials and strategies for nerve regeneration.

Nerve regeneration is a complex biological phenomenon. Once the nervous system is impaired, its recovery is difficult and malfunctions in other parts of the body may occur because mature neurons do not undergo cell division. To increase the prospects of axonal regeneration and functional recovery, researches have focused on designing "nerve guidance channels" or "nerve conduits." When developing ideal tissue-engineered nerve conduits, several components come to mind. They include a biodegradable and porous channel wall, the ability to deliver bioactive growth factors, incorporation of support cells, an internal oriented matrix to support cell migration, intraluminal channels to mimic the structure of nerve fascicles, and electrical activities. This article reviews the factors that are critical for nerve repair, and the advanced technologies that are explored to fabricate nerve conduits. To more accurately mimic natural repair in the body, recent studies have focused on the use of various advanced approaches to create ideal nerve conduits that combine multiple stimuli in an effort to better mimic the complex signals normally found in the body.

[1]  G Lundborg,et al.  A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance. , 2000, Journal of Hand Surgery-American Volume.

[2]  M. Dauge,et al.  Nerve repair using a composite graft of vein and denatured skeletal muscle: morphologic analysis. , 2002, Journal of reconstructive microsurgery.

[3]  Tessa Hadlock,et al.  Manufacture of porous polymer nerve conduits by a novel low-pressure injection molding process. , 2003, Biomaterials.

[4]  Zheng-rong Chen,et al.  Fabricating autologous tissue to engineer artificial nerve , 2002, Microsurgery.

[5]  M. R. Ahmed,et al.  Multilayered peptide incorporated collagen tubules for peripheral nerve repair. , 2004, Biomaterials.

[6]  C. McCaig Nerve branching is induced and oriented by a small applied electric field. , 1990, Journal of cell science.

[7]  F. Lin,et al.  An in vivo study of tricalcium phosphate and glutaraldehyde crosslinking gelatin conduits in peripheral nerve repair. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[8]  Tatsuo Nakamura,et al.  Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA)–collagen tube filled with laminin-coated collagen fibers: a histological and electrophysiological evaluation of regenerated nerves , 2000, Brain Research.

[9]  Barbara Grimpe,et al.  The extracellular matrix in axon regeneration. , 2002, Progress in brain research.

[10]  Kam W Leong,et al.  Peripheral nerve regeneration by microbraided poly(L-lactide-co-glycolide) biodegradable polymer fibers. , 2004, Journal of biomedical materials research. Part A.

[11]  J. G. van Dijk,et al.  Obstetric lesions of the brachial plexus , 2001, Muscle & nerve.

[12]  F. Gage,et al.  Isolation, characterization, and use of stem cells from the CNS. , 1995, Annual review of neuroscience.

[13]  G. Lundborg,et al.  Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction , 1998, Brain Research.

[14]  J. Trachtenberg,et al.  Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions , 1996, Trends in Neurosciences.

[15]  Khoi D. Nguyen,et al.  Artificial Nerve Graft Using Collagen as an Extracellular Matrix for Nerve Repair Compared with Sutured Autograft in a Rat Model , 1990, Annals of plastic surgery.

[16]  G. Lundborg,et al.  Vascular endothelial growth factor stimulates Schwann cell invasion and neovascularization of acellular nerve grafts , 1999, Brain Research.

[17]  J. Tanaka,et al.  Tendon chitosan tubes covalently coupled with synthesized laminin peptides facilitate nerve regeneration in vivo , 2003, Journal of neuroscience research.

[18]  Lauren Flynn,et al.  Fiber templating of poly(2-hydroxyethyl methacrylate) for neural tissue engineering. , 2003, Biomaterials.

[19]  R. Tranquillo,et al.  Guided Neurite Elongation and Schwann Cell Invasion into Magnetically Aligned Collagen in Simulated Peripheral Nerve Regeneration , 1999, Experimental Neurology.

[20]  P. Ma,et al.  Microtubular architecture of biodegradable polymer scaffolds. , 2001, Journal of biomedical materials research.

[21]  M. Shoichet,et al.  Long-term in vivo biomechanical properties and biocompatibility of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) nerve conduits. , 2005, Biomaterials.

[22]  D. Erdmann,et al.  The Use of Cultured Schwann Cells in Nerve Repair in a Rabbit Hind-Limb Model , 1996, Journal of reconstructive microsurgery.

[23]  P H Robinson,et al.  Nerve regeneration through a two‐ply biodegradable nerve guide in the rat and the influence of ACTH4‐9 nerve growth factor , 1991, Microsurgery.

[24]  H. Buettner,et al.  Oriented Schwann Cell Monolayers for Directed Neurite Outgrowth , 2004, Annals of Biomedical Engineering.

[25]  G. Lundborg,et al.  Resorbable filament structures as a scaffold for matrix formation and axonal growth in bioartificial nerve grafts: long term observations. , 1997, Restorative neurology and neuroscience.

[26]  S. Mackinnon,et al.  The Peripheral Nerve Allograft: A Dose-Response Curve in the Rat Immunosuppressed with Cyclosporin A , 1988, Plastic and Reconstructive Surgery.

[27]  J. Rosen,et al.  The Artificial Nerve Graft: A Comparison of Blended Elastomer-Hydrogel with Polyglycolic Acid Conduits , 1991, Journal of reconstructive microsurgery.

[28]  M. Tuszynski,et al.  The fabrication and characterization of linearly oriented nerve guidance scaffolds for spinal cord injury. , 2004, Biomaterials.

[29]  Susan E. Mackinnon,et al.  Clinical Nerve Reconstruction with a Bioabsorbable Polyglycolic Acid Tube , 1990, Plastic and reconstructive surgery.

[30]  R. Bunge The role of the Schwann cell in trophic support and regeneration , 1994, Journal of Neurology.

[31]  S. Hsu,et al.  The effects of low-intensity ultrasound on peripheral nerve regeneration in poly(DL-lactic acid-co-glycolic acid) conduits seeded with Schwann cells. , 2004, Ultrasound in medicine & biology.

[32]  M. Tuszynski,et al.  Neurotrophic factors, gene therapy, and neural stem cells for spinal cord repair , 2002, Brain Research Bulletin.

[33]  P. Thanos,et al.  Ultrastructure and Cellular Biology of Nerve Regeneration , 1998, Journal of reconstructive microsurgery.

[34]  A. Zalewski,et al.  Rejection of nerve allografts after cessation of immunosuppression with cyclosporin A. , 1981, Transplantation.

[35]  Min Zhao,et al.  Controlling cell behavior electrically: current views and future potential. , 2005, Physiological reviews.

[36]  J. Terzis,et al.  Historical and Basic Science Review: Past, Present, and Future of Nerve Repair , 1997, Journal of reconstructive microsurgery.

[37]  J. Vacanti,et al.  A polymer foam conduit seeded with Schwann cells promotes guided peripheral nerve regeneration. , 2000, Tissue engineering.

[38]  Scott R. Whittemore,et al.  Pluripotent Stem Cells Engrafted into the Normal or Lesioned Adult Rat Spinal Cord Are Restricted to a Glial Lineage , 2001, Experimental Neurology.

[39]  H M Buettner,et al.  Microcontact printing of proteins on oxygen plasma-activated poly(methyl methacrylate). , 2004, Biomaterials.

[40]  S. Kay,et al.  Obstetrical brachial palsy. , 1998, British journal of plastic surgery.

[41]  U. Rutishauser Adhesion molecules of the nervous system , 1993, Current Opinion in Neurobiology.

[42]  J. Benoit,et al.  Pharmacologically active microcarriers: a tool for cell therapy. , 2005, Biomaterials.

[43]  N. Kleitman,et al.  Axonal regeneration into Schwann cell‐seeded guidance channels grafted into transected adult rat spinal cord , 1995, The Journal of comparative neurology.

[44]  J. Kocsis,et al.  Cell transplantation of peripheral-myelin-forming cells to repair the injured spinal cord. , 2002, Journal of rehabilitation research and development.

[45]  J. Fawcett,et al.  Chondroitin sulphate proteoglycans: inhibitory components of the glial scar. , 2001, Progress in brain research.

[46]  M. Tuszynski,et al.  Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury , 2001, The Journal of physiology.

[47]  M. Romero,et al.  Adenoviral‐mediated gene transfer to enhance neuronal survival, growth, and regeneration , 1999, Journal of neuroscience research.

[48]  R Langer,et al.  A tissue-engineered conduit for peripheral nerve repair. , 1998, Archives of otolaryngology--head & neck surgery.

[49]  S. Mallapragada,et al.  Micropatterned Schwann cell-seeded biodegradable polymer substrates significantly enhance neurite alignment and outgrowth. , 2001, Tissue engineering.

[50]  J. Bain Peripheral nerve and neuromuscular allotransplantation: Current status , 2000, Microsurgery.

[51]  D. Maysinger,et al.  Drug delivery to the nervous system. , 1997, Trends in biotechnology.

[52]  Paola Bovolenta,et al.  Nervous system proteoglycans as modulators of neurite outgrowth , 2000, Progress in Neurobiology.

[53]  J. Verhaagen,et al.  Viral vectors, tools for gene transfer in the nervous system , 1998, Progress in Neurobiology.

[54]  J. J. Bernstein,et al.  Experimental spinal cord transplantation as a mechanism of spinal cord regeneration , 1995, Paraplegia.

[55]  S. Ichinose,et al.  Hydroxyapatite-coated tendon chitosan tubes with adsorbed laminin peptides facilitate nerve regeneration in vivo , 2003, Brain Research.

[56]  A. Tessler,et al.  Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres derived from embryonic rat spinal cord , 2000, Brain Research.

[57]  James W. Fawcett,et al.  Building a Bridge: Engineering Spinal Cord Repair , 2002, Experimental Neurology.

[58]  R. Eberhart,et al.  Laminin-coated poly(L-lactide) filaments induce robust neurite growth while providing directional orientation. , 2000, Journal of biomedical materials research.

[59]  J. Fraher The transitional zone and CNS regeneration , 1999, Journal of anatomy.

[60]  M. Beattie,et al.  Review of current evidence for apoptosis after spinal cord injury. , 2000, Journal of neurotrauma.

[61]  T. Carlstedt Nerve fibre regeneration across the peripheral–central transitional zone , 1997, Journal of anatomy.

[62]  J. M. Schakenraad,et al.  A new PLLA/PCL copolymer for nerve regeneration , 1993 .

[63]  R. Franklin,et al.  Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes , 2000, Glia.

[64]  I. Yannas,et al.  Recent advances in tissue synthesis in vivo by use of collagen-glycosaminoglycan copolymers. , 1996, Biomaterials.

[65]  M. Wiberg,et al.  A composite poly‐hydroxybutyrate–glial growth factor conduit for long nerve gap repairs , 2003, Journal of anatomy.

[66]  A. Awaya,et al.  Basic Behavior of Migratory Schwann Cells in Peripheral Nerve Regeneration , 1996, Experimental Neurology.

[67]  M. Oka,et al.  Collagen filaments as a scaffold for nerve regeneration. , 2001, Journal of biomedical materials research.

[68]  Mary Bartlett Bunge,et al.  Book Review: Bridging Areas of Injury in the Spinal Cord , 2001 .

[69]  Micropatterned polymer substrates control alignment of proliferating Schwann cells to direct neuronal regeneration , 2005 .

[70]  J. Rosen,et al.  Artificial nerve graft using glycolide trimethylene carbonate as a nerve conduit filled with collagen compared to sutured autograft in a rat model. , 1992, Journal of rehabilitation research and development.

[71]  G. Terenghi,et al.  Peripheral nerve regeneration and neurotrophic factors , 1999, Journal of anatomy.

[72]  Yoshihiro Mizutani,et al.  Sciatic nerve regeneration navigated by laminin-fibronectin double coated biodegradable collagen grafts in rats , 1994, Brain Research.

[73]  R. Franklin,et al.  Do olfactory glia have advantages over Schwann cells for CNS repair? , 1997, Journal of neuroscience research.

[74]  R. Giardino,et al.  Preparation of a new nerve guide from a poly(L-lactide-co-6-caprolactone). , 1994, Biomaterials.

[75]  K. Tohyama,et al.  Long Acellular Nerve Transplants for Allogeneic Grafting and the Effects of Basic Fibroblast Growth Factor on the Growth of Regenerating Axons in Dogs: A Preliminary Report , 1998, Experimental Neurology.

[76]  L. Barrett,et al.  Gene therapy for central nervous system repair. , 2001, Current opinion in molecular therapeutics.

[77]  N. Chauhan,et al.  Carbon filaments direct the growth of postlesional plastic axons after spinal cord injury , 1999, International Journal of Developmental Neuroscience.

[78]  G. Keilhoff,et al.  Reconstruction of peripheral nerves using acellular nerve grafts with implanted cultured Schwann cells , 2002, Microsurgery.

[79]  R. Brown,et al.  Neurotrophin‐3 Delivered Locally via Fibronectin Mats Enhances Peripheral Nerve Regeneration , 1997, The European journal of neuroscience.

[80]  M. Akagi,et al.  Bridging a 30-mm nerve defect using collagen filaments. , 2003, Journal of biomedical materials research. Part A.

[81]  R Langer,et al.  Stimulation of neurite outgrowth using an electrically conducting polymer. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[82]  C. Schmidt,et al.  Engineering strategies for peripheral nerve repair. , 2000, Clinics in plastic surgery.

[83]  V. Hentz,et al.  A comparison of suture and tubulization nerve repair techniques in a primate. , 1991, The Journal of hand surgery.

[84]  E. Marani,et al.  Adhesion and proliferation of human Schwann cells on adhesive coatings. , 2004, Biomaterials.

[85]  P. Caliceti,et al.  Peripheral nerve repair using a poly(organo)phosphazene tubular prosthesis. , 1995, Biomaterials.

[86]  K. Marra,et al.  Multi-channeled biodegradable polymer/CultiSpher composite nerve guides. , 2004, Biomaterials.

[87]  Rajiv Midha,et al.  Peripheral nerve regeneration through a synthetic hydrogel nerve tube. , 2005, Restorative neurology and neuroscience.

[88]  Yi‐Cheng Huang,et al.  Manufacture of porous polymer nerve conduits through a lyophilizing and wire-heating process. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[89]  Xavier Navarro,et al.  Magnetically Aligned Collagen Gel Filling a Collagen Nerve Guide Improves Peripheral Nerve Regeneration , 1999, Experimental Neurology.

[90]  P H Robinson,et al.  Light-microscopic and electron-microscopic evaluation of short-term nerve regeneration using a biodegradable poly(DL-lactide-epsilon-caprolacton) nerve guide. , 1996, Journal of biomedical materials research.

[91]  Michael Sendtner,et al.  Microencapsulated Ciliary Neurotrophic Factor: Physical Properties and Biological Activities , 1996, Experimental Neurology.

[92]  Robert Langer,et al.  Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[93]  W. Gispen,et al.  Spinal cord injury: bridging the lesion and the role of neurotrophic factors in repair. , 1998, Progress in brain research.

[94]  X. Cao,et al.  Delivering neuroactive molecules from biodegradable microspheres for application in central nervous system disorders. , 1999, Biomaterials.

[95]  C. Heath,et al.  The development of bioartificial nerve grafts for peripheral-nerve regeneration. , 1998, Trends in biotechnology.

[96]  P H Robinson,et al.  Two-ply biodegradable nerve guide: basic aspects of design, construction and biological performance. , 1990, Biomaterials.