Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration

OBJECTIVE The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. APPROACH A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. MAIN RESULTS Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. SIGNIFICANCE Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

[1]  Yi Sun,et al.  Neural Stem Cells Enhance Nerve Regeneration after Sciatic Nerve Injury in Rats , 2012, Molecular Neurobiology.

[2]  M. Wiberg,et al.  New Fibrin Conduit for Peripheral Nerve Repair , 2008, Journal of reconstructive microsurgery.

[3]  M. Brenner,et al.  Repair of Motor Nerve Gaps With Sensory Nerve Inhibits Regeneration in Rats , 2006, The Laryngoscope.

[4]  V. Carriel,et al.  Evaluation of myelin sheath and collagen reorganization pattern in a model of peripheral nerve regeneration using an integrated histochemical approach , 2011, Histochemistry and Cell Biology.

[5]  Christina K. Magill,et al.  Processed allografts and type I collagen conduits for repair of peripheral nerve gaps , 2009, Muscle & nerve.

[6]  Y. Barrandon,et al.  LONG-TERM REGENERATION OF HUMAN EPIDERMIS ON THIRD DEGREE BURNS TRANSPLANTED WITH AUTOLOGOUS CULTURED EPITHELIUM GROWN ON A FIBRIN MATRIX1,2 , 2000, Transplantation.

[7]  P. Kingham,et al.  Extracellular matrix molecules enhance the neurotrophic effect of Schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions. , 2013, Tissue engineering. Part A.

[8]  M. Shoichet,et al.  Peripheral nerve regeneration through guidance tubes , 2004, Neurological research.

[9]  M. Alaminos,et al.  In vitro Cytokeratin Expression Profiling of Human Oral Mucosa Substitutes Developed by Tissue Engineering , 2009, The International journal of artificial organs.

[10]  C. Vleggeert-Lankamp,et al.  The role of evaluation methods in the assessment of peripheral nerve regeneration through synthetic conduits: a systematic review. Laboratory investigation. , 2007, Journal of neurosurgery.

[11]  M. Alaminos,et al.  Pluripotential Differentiation Capability of Human Adipose-derived Stem Cells in a Novel Fibrin-agarose Scaffold , 2011, Journal of biomaterials applications.

[12]  Uma Maheswari Krishnan,et al.  Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration , 2009, Journal of Biomedical Science.

[13]  Xiaosong Gu,et al.  Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration , 2011, Progress in Neurobiology.

[14]  M. Siemionow,et al.  The epineural sleeve technique for nerve graft reconstruction enhances nerve recovery , 2008, Microsurgery.

[15]  R. Weber,et al.  A Randomized Prospective Study of Polyglycolic Acid Conduits for Digital Nerve Reconstruction in Humans , 2000, Plastic and reconstructive surgery.

[16]  B. Munder,et al.  An in vivo engineered nerve conduit—fabrication and experimental study in rats , 2011, Microsurgery.

[17]  Michael J Yaszemski,et al.  Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit. , 2010, Biomaterials.

[18]  S. Kim,et al.  Peripheral Nerve Regeneration Using a Three Dimensionally Cultured Schwann Cell Conduit , 2007, The Journal of craniofacial surgery.

[19]  M. Alaminos,et al.  Sequential development of intercellular junctions in bioengineered human corneas , 2009, Journal of tissue engineering and regenerative medicine.

[20]  M. Alaminos,et al.  In vitro and in vivo cytokeratin patterns of expression in bioengineered human periodontal mucosa. , 2009, Journal of periodontal research.

[21]  M. Wiberg,et al.  Adipose-derived stem cells enhance peripheral nerve regeneration. , 2010, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[22]  Hui Zhao,et al.  The use of laminin modified linear ordered collagen scaffolds loaded with laminin-binding ciliary neurotrophic factor for sciatic nerve regeneration in rats. , 2011, Biomaterials.

[23]  L. Kalliainen,et al.  Collagen Tube Conduits in Peripheral Nerve Repair: A Retrospective Analysis , 2010, Hand.

[24]  M. Alaminos,et al.  Rheological characterization of human fibrin and fibrin–agarose oral mucosa substitutes generated by tissue engineering , 2012, Journal of tissue engineering and regenerative medicine.

[25]  H. Machens,et al.  Überbrückung peripherer Nervendefekte durch den Einsatz von Nervenröhrchen , 2007, Der Chirurg.

[26]  V. Hentz Modern surgical management of peripheral nerve gap , 2011 .

[27]  P. Tos,et al.  Schwann-Cell Proliferation in Muscle-Vein Combined Conduits for Bridging Rat Sciatic Nerve Defects , 2003, Journal of reconstructive microsurgery.

[28]  A. Baptista,et al.  Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury. , 2012, Tissue engineering. Part A.

[29]  Andrés Hurtado,et al.  Creation of highly aligned electrospun poly-L-lactic acid fibers for nerve regeneration applications , 2009, Journal of neural engineering.

[30]  S. Arias-Santiago,et al.  Epithelial and Stromal Developmental Patterns in a Novel Substitute of the Human Skin Generated with Fibrin-Agarose Biomaterials , 2011, Cells Tissues Organs.

[31]  Surya K Mallapragada,et al.  Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration , 2004, Journal of neural engineering.

[32]  F. Zor,et al.  Regeneration and repair of peripheral nerves with different biomaterials: Review , 2010, Microsurgery.

[33]  S. Ramakrishna,et al.  In vivo study of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration , 2010, Journal of neural engineering.

[34]  Adina Haug,et al.  US Food and Drug Administration/Conformit Europe-approved absorbable nerve conduits for clinical repair of peripheral and cranial nerves. , 2009, Annals of plastic surgery.

[35]  M. Alaminos,et al.  The effects of fibrin and fibrin‐agarose on the extracellular matrix profile of bioengineered oral mucosa , 2013, Journal of tissue engineering and regenerative medicine.

[36]  Ida K. Fox,et al.  Effects of motor versus sensory nerve grafts on peripheral nerve regeneration , 2004, Experimental Neurology.

[37]  M. Cámara,et al.  Failed digital nerve reconstruction by foreign body reaction to Neurolac® nerve conduit , 2009, Microsurgery.

[38]  R. Ghinea,et al.  Investigating a novel nanostructured fibrin-agarose biomaterial for human cornea tissue engineering: rheological properties. , 2011, Journal of the mechanical behavior of biomedical materials.

[39]  M. Alaminos,et al.  Histological and histochemical evaluation of human oral mucosa constructs developed by tissue engineering. , 2007, Histology and histopathology.

[40]  James J. Yoo,et al.  End-to-side neurorrhaphy using an electrospun PCL/collagen nerve conduit for complex peripheral motor nerve regeneration. , 2012, Biomaterials.

[41]  Shipu Li,et al.  PDLLA/chondroitin sulfate/chitosan/NGF conduits for peripheral nerve regeneration. , 2011, Biomaterials.

[42]  John W Haycock,et al.  Next generation nerve guides: materials, fabrication, growth factors, and cell delivery. , 2012, Tissue engineering. Part B, Reviews.

[43]  D. Nair,et al.  Peripheral Nerve Defect Repair With Epineural Tubes Supported With Bone Marrow Stromal Cells: A Preliminary Report , 2011, Annals of plastic surgery.

[44]  A. Chong,et al.  Early Clinical Experience With Collagen Nerve Tubes in Digital Nerve Repair , 2009 .

[45]  G. Lundborg [Regeneration after peripheral nerve injury - a biological and clinical problem]. , 1982, Läkartidningen.

[46]  David L Kaplan,et al.  Biomaterials for the development of peripheral nerve guidance conduits. , 2012, Tissue engineering. Part B, Reviews.

[47]  M. Alaminos,et al.  Time‐course study of histological and genetic patterns of differentiation in human engineered oral mucosa , 2007, Journal of tissue engineering and regenerative medicine.

[48]  L. Yao,et al.  A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery , 2012, Journal of The Royal Society Interface.

[49]  Y. Koyama,et al.  Enhancement of peripheral nerve regeneration using bioabsorbable polymer tubes packed with fibrin gel. , 2007, Artificial organs.

[50]  M. M. Pérez,et al.  Transparency in a Fibrin and Fibrin–Agarose Corneal Stroma Substitute Generated by Tissue Engineering , 2011, Cornea.

[51]  A. Shin,et al.  Treatment of a segmental nerve defect in the rat with use of bioabsorbable synthetic nerve conduits: a comparison of commercially available conduits. , 2009, The Journal of bone and joint surgery. American volume.

[52]  D. Carey,et al.  Regulation of Schwann cell function by the extracellular matrix , 2008, Glia.

[53]  D. J. Smith,et al.  FDA approved guidance conduits and wraps for peripheral nerve injury: A review of materials and efficacy , 2013 .

[54]  J. Priestley,et al.  Regenerative potential of silk conduits in repair of peripheral nerve injury in adult rats. , 2012, Biomaterials.

[55]  Miguel Alaminos,et al.  Construction of a complete rabbit cornea substitute using a fibrin-agarose scaffold. , 2006, Investigative ophthalmology & visual science.

[56]  S. Arias-Santiago,et al.  A Novel Histochemical Method for a Simultaneous Staining of Melanin and Collagen Fibers , 2011, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[57]  P. Tos,et al.  Chapter 3: Histology of the peripheral nerve and changes occurring during nerve regeneration. , 2009, International review of neurobiology.

[58]  L. Novikova,et al.  Biodegradable fibrin conduit promotes long-term regeneration after peripheral nerve injury in adult rats. , 2010, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[59]  Kai Gong,et al.  Chitosan/silk fibroin-based tissue-engineered graft seeded with adipose-derived stem cells enhances nerve regeneration in a rat model , 2011, Journal of materials science. Materials in medicine.

[60]  Stefano Geuna,et al.  Nerve repair by means of tubulization: Literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair , 2005, Microsurgery.