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Silk Biomaterials in Peripheral Nerve Tissue Engineering

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Peripheral Nerve Tissue Engineering and Regeneration

Abstract

Peripheral nerve regeneration represents a major clinical challenge especially if nerve tissue must be replaced to regain function. Repair of critical size nerve defects with development of optimal nerve conduits is the subject of numerous in vitro and in vivo studies. In this regard, natural silk and silk fibroin are widely used materials for tissue engineering of peripheral nerve conduits for implantation. In this chapter, a broad overview of pathophysiological changes and parameters of nerve injuries for repair techniques to achieve nerve regeneration is presented with an emphasis on silk as a biomaterial in tissue engineering. Differences in the variety of silk sources with their individual advantages and disadvantages are discussed with a focus on nerve regeneration. Furthermore, additional components for enhancement of nerve regeneration which must be considered including extracellular matrix proteins, growth factors, peptides sequences, and cellular support to biofunctionalize silk-based nerve conduits are summarized. Finally, clinical translation using experimental in vivo models is presented.

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References

  • Agnarsson I, Kuntner M, Blackledge TA (2010) Bioprospecting finds the toughest biological material: extraordinary silk from a giant riverine orb spider. PLoS One 5(9):e11234

    Article  Google Scholar 

  • Aigner TB, DeSimone E, Scheibel T (2018) Biomedical applications of recombinant silk-based materials. Adv Mater 30(19):e1704636

    Article  Google Scholar 

  • Allmeling C, Jokuszies A, Reimers K, Kall S, Vogt PM (2006) Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit. J Cell Mol Med 10(3):770–777

    Article  Google Scholar 

  • Allmeling C, Jokuszies A, eimers K, Kall S, Choi CY, Brandes G, Kasper C, Scheper T, Guggenheim M, Vogt PM (2008) Spider silk fibres in artificial nerve constructs promote peripheral nerve regeneration. Cell Prolif 41(3):408–420

    Article  Google Scholar 

  • Altman, G. H., F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, . Chen, H. Lu, J. Richmond and D. L. Kaplan (2003). Silk-based biomaterials. Biomaterials 24(3): 401–416

    Article  Google Scholar 

  • Arcidiacono S, Mello C, Kaplan D, Cheley S, Bayley H (1998) Purification and characterization of recombinant spider silk expressed in Escherichia coli. Appl Microbiol Biotechnol 49(1):31–38

    Article  Google Scholar 

  • Arslantunali D, Dursun T, Yucel D, Hasirci N, Hasirci V (2014) Peripheral nerve conduits: technology update. Med Devices (Auckl) 7:405–424

    Google Scholar 

  • Arthur-Farraj PJ, Latouche M, Wilton DK, Quintes S, Chabrol E, Banerjee A, Woodhoo A, Jenkins B, Rhman M, Turmaine M, Wicher GK, Mitter R, Greensmith L, Behrens A, Raivich G, Mirsky R, Jessen KR (2012) C-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron 75(4):633–647

    Article  Google Scholar 

  • Bai S, Zhang W, Lu Q, Ma Q, Kaplan DL, Zhu H (2014) Silk nanofiber hydrogels with tunable modulus to regulate nerve stem cell fate. J Mater Chem B 2(38):6590–6600

    Article  Google Scholar 

  • Barr LA, Fahnestock SR, Yang J (2004) Production and purification of recombinant DP1B silk-like protein in plants. Mol Breed 13(4):345–356

    Article  Google Scholar 

  • Bini E, Foo CW, Huang J, Karageorgiou V, Kitchel B, Kaplan DL (2006) RGD-functionalized bioengineered spider dragline silk biomaterial. Biomacromolecules 7(11):3139–3145

    Article  Google Scholar 

  • Blamires SJ, Blackledge TA, Tso IM (2017) Physicochemical property variation in spider silk: ecology, evolution, and synthetic production. Annu Rev Entomol 62:443–460

    Article  Google Scholar 

  • Bogush VG, Sokolova OS, Davydova LI, Klinov DV, Sidoruk KV, Esipova NG, Neretina TV, Orchanskyi IA, Makeev VY, Tumanyan VG, Shaitan KV, Debabov VG, Kirpichnikov MP (2009) A novel model system for design of biomaterials based on recombinant analogs of spider silk proteins. J Neuroimmune Pharmacol 4(1):17–27

    Article  Google Scholar 

  • Boyd JG, Gordon T (2003) Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury. Mol Neurobiol 27(3):277–324

    Article  Google Scholar 

  • Brooks AE, Nelson SR, Jones JA, Koenig C, Hinman M, Stricker S, Lewis RV (2008) Distinct contributions of model MaSp1 and MaSp2 like peptides to the mechanical properties of synthetic major ampullate silk fibers as revealed in silico. Nanotechnol Sci Appl 1:9–16

    Article  Google Scholar 

  • Brown CN, Finch JG (2010) Which mesh for hernia repair? Ann R Coll Surg Engl 92(4):272–278

    Article  Google Scholar 

  • Cameron HD (2005) Chapter 73: an etymological dictionary of North American spider genus names. In: Spiders of North America: an identification manual. American Arachnological Society, New Hampshire

    Google Scholar 

  • Cao Y, Wang B (2009) Biodegradation of silk biomaterials. Int J Mol Sci 10(4):1514–1524

    Article  Google Scholar 

  • Cao TT, Zhang YQ (2016) Processing and characterization of silk sericin from Bombyx mori and its application in biomaterials and biomedicines. Mater Sci Eng C Mater Biol Appl 61:940–952

    Article  Google Scholar 

  • Chen P, Tong XL, Fu MY, Hu H, Song JB, He SZ, Gai TT, Dai FY, Lu C (2016) Molecular mapping and characterization of the silkworm apodal mutant. Sci Rep 6:18956

    Article  Google Scholar 

  • Conrad U, Fiedler U (1998) Compartment-specific accumulation of recombinant immunoglobulins in plant cells: an essential tool for antibody production and immunomodulation of physiological functions and pathogen activity. Springer, Dordrecht

    Google Scholar 

  • Craig CL (1997) Evolution of arthropod silks. Annu Rev Entomol 42:231–267

    Article  Google Scholar 

  • Craig CL, Hsu M, Kaplan D, Pierce NE (1999) A comparison of the composition of silk proteins produced by spiders and insects. Int J Biol Macromol 24(2–3):109–118

    Article  Google Scholar 

  • Crapo PM, Gilbert TW, Badylak SF (2011) An overview of tissue and whole organ decellularization processes. Biomaterials 32(12):3233–3243

    Article  Google Scholar 

  • Cregg J (2007) DNA-mediated transformation. Methods Mol Biol 389:27–42

    Article  Google Scholar 

  • Cunniff PM, Fossey SA, Auerbach MA, Song JW, Kaplan DL, Adams WW, Eby RK, Mahoney D, Vezie DL (1994) Mechanical and thermal properties of dragline silk from the spider Nephila clavipes. Polym Adv Technol 5(8):401–410

    Article  Google Scholar 

  • Daroff RBJ, Joseph, Mazziotta JC, Pomeroy SL, Bradley WG (2016) Bradley’s neurology in clinical practice. Elsevier, New York

    Google Scholar 

  • Das S, Sharma M, Saharia D, Sarma KK, Sarma MG, Borthakur BB, Bora U (2015) In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration. Biomaterials 62:66–75

    Article  Google Scholar 

  • Das S, Sharma M, Saharia D, Sarma KK, Muir EM, Bora U (2017) Electrospun silk-polyaniline conduits for functional nerve regeneration in rat sciatic nerve injury model. Biomed Mater 12(4):045025

    Article  Google Scholar 

  • de Luca AC, Lacour SP, Raffoul W, di Summa PG (2014) Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration? Neural Regen Res 9(22): 1943–1948

    Google Scholar 

  • DeFrancesco L (2017) Hanging on a thread. Nat Biotechnol 35:496–499

    Article  Google Scholar 

  • di Summa PG, Kingham PJ, Raffoul W, Wiberg M, Terenghi G, Kalbermatten DF (2010) Adipose-derived stem cells enhance peripheral nerve regeneration. J Plast Reconstr Aesthet Surg 63(9):1544–1552

    Article  Google Scholar 

  • Dinis TM, Vidal G, Jose RR, Vigneron P, Bresson D, Fitzpatrick V, Marin F, Kaplan DL, Egles C (2014) Complementary effects of two growth factors in multifunctionalized silk nanofibers for nerve reconstruction. PLoS One 9(10):e109770

    Article  Google Scholar 

  • Dinis TM, Elia R, Vidal G, Dermigny Q, Denoeud C, Kaplan DL, Egles C, Marin F (2015) 3D m channel bi-functionalized silk electrospun conduits for peripheral nerve regeneration. J Mech Behav Biomed Mater 41:43–55

    Article  Google Scholar 

  • El-Bassyouni H, Mohammed M. Ahmed (2018). Genome editing: a review of literature, LAP LAMBERT Academic Publishing, Beau Bassin, Mauritius

    Google Scholar 

  • Elbert DL (2011) Bottom-up tissue engineering. Curr Opin Biotechnol 22(5):674–680

    Article  Google Scholar 

  • Evans GR, Brandt K, Katz S, Chauvin P, Otto L, Bogle M, Wang B, Meszlenyi RK, Lu L, Mikos AG, Patrick CW Jr (2002) Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration. Biomaterials 23(3):841–848

    Article  Google Scholar 

  • Faroni A, Terenghi G, Reid AJ (2013) Adipose-derived stem cells and nerve regeneration: promises and pitfalls. Int Rev Neurobiol 108:121–136

    Article  Google Scholar 

  • Foelix RF (1996) Biology of spiders. Oxford University Press, New York

    Google Scholar 

  • Freddi G, Mossotti R, Innocenti R (2003) Degumming of silk fabric with several proteases. J Biotechnol 106(1):101–112

    Article  Google Scholar 

  • Gage LP, Manning RF (1980) Internal structure of the silk fibroin gene of Bombyx mori. I the fibroin gene consists of a homogeneous alternating array of repetitious crystalline and amorphous coding sequences. J Biol Chem 255(19):9444–9450

    Article  Google Scholar 

  • Gatesy J, Hayashi C, Motriuk D, Woods J, Lewis R (2001) Extreme diversity, conservation, and convergence of spider silk fibroin sequences. Science 291(5513):2603–2605

    Article  Google Scholar 

  • Gellynck K, Verdonk P, Forsyth R, Almqvist K, Van Nimmen E, Gheysens T, Mertens J, Van Langenhove L, Kiekens P, Verbruggen G (2008) Biocompatibility and biodegradability of spider egg sac silk. J Mater Sci Mater Med 19(8):2963–2970

    Article  Google Scholar 

  • Georgiou M, Golding JP, Loughlin AJ, Kingham PJ, Phillips JB (2015) Engineered neural tissue with aligned, differentiated adipose-derived stem cells promotes peripheral nerve regeneration across a critical sized defect in rat sciatic nerve. Biomaterials 37:242–251

    Article  Google Scholar 

  • Gerritsen VB (2002) The tiptoe of an airbus. Prot Spot 24:1–2

    Google Scholar 

  • Ghaznavi AM, Kokai LE, Lovett ML, Kaplan DL, Marra KG (2011) Silk fibroin conduits: a cellular and functional assessment of peripheral nerve repair. Ann Plast Surg 66(3):273–279

    Article  Google Scholar 

  • Goldman IL, Kadulin SG, Razin SV (2004) Transgenic animals in medicine: integration and expression of foreign genes, theoretical and applied aspects. Med Sci Monit 10(11):Ra274–Ra285

    Google Scholar 

  • Goldsmith MR, Shimada T, Abe H (2005) The genetics and genomics of the silkworm, Bombyx mori. Annu Rev Entomol 50(1):71–100

    Article  Google Scholar 

  • Gosline JM, Guerette PA, Ortlepp CS, Savage KN (1999) The mechanical design of spider silks: from fibroin sequence to mechanical function. J Exp Biol 202(23):3295–3303

    Article  Google Scholar 

  • Grinsell D, Keating CP (2014) Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int 2014:698256

    Article  Google Scholar 

  • Gu Y, Zhu J, Xue C, Li Z, Ding F, Yang Y, Gu X (2014) Chitosan/silk fibroin-based, Schwann cell-derived extracellular matrix-modified scaffolds for bridging rat sciatic nerve gaps. Biomaterials 35(7):2253–2263

    Article  Google Scholar 

  • Gyori E, Radtke C, Gordon T, Borschel GH (2018) [Pathway protection – enhanced motoneuron regeneration by end-to-side coaptation of sensory axons]. Handchir Mikrochir Plast Chir 50(5):341–347

    Google Scholar 

  • Haastert K, Joswig H, Jaschke KA, Samii M, Grothe C (2010) Nerve repair by end-to-side nerve coaptation: histologic and morphometric evaluation of axonal origin in a rat sciatic nerve model. Neurosurgery 66(3):567–576. discussion 576–567

    Article  Google Scholar 

  • Hayashi CY, Lewis RV (2000) Molecular architecture and evolution of a modular spider silk protein gene. Science 287(5457):1477–1479

    Article  Google Scholar 

  • Heidebrecht A, Scheibel T (2013) Chapter four – recombinant production of spider silk proteins. Adv Appl Microbiol 82:115–153

    Article  Google Scholar 

  • Heim M, Keerl D, Scheibel T (2009) Spider silk: from soluble protein to extraordinary fiber. Angew Chem Int Ed Eng 48(20):3584–3596

    Article  Google Scholar 

  • Hersel U, Dahmen C, Kessler H (2003) RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials 24(24):4385–4415

    Article  Google Scholar 

  • Hinman MB, Lewis RV (1992) Isolation of a clone encoding a second dragline silk fibroin. Nephila clavipes dragline silk is a two-protein fiber. J Biol Chem 267(27):19320–19324

    Article  Google Scholar 

  • Hoke A (2006) Mechanisms of disease: what factors limit the success of peripheral nerve regeneration in humans? Nat Clin Pract Neurol 2(8):448–454

    Article  Google Scholar 

  • Hood B, Levene HB, Levi AD (2009) Transplantation of autologous Schwann cells for the repair of segmental peripheral nerve defects. Neurosurg Focus 26(2):E4

    Article  Google Scholar 

  • Hopkins AM, De Laporte L, Tortelli F, Spedden E, Staii C, Atherton TJ, Hubbell JA, Kaplan DL (2013) Silk hydrogels as soft substrates for neural tissue engineering. Adv Funct Mater 23(41):5140–5149

    Article  Google Scholar 

  • Horan RL, Antle K, Collette AL, Wang Y, Huang J, Moreau JE, Volloch V, Kaplan DL, Altman GH (2005) In vitro degradation of silk fibroin. Biomaterials 26(17):3385–3393

    Article  Google Scholar 

  • Hu A, Zuo B, Zhang F, Lan Q, Zhang H (2012) Electrospun silk fibroin nanofibers promote Schwann cell adhesion, growth and proliferation. Neural Regen Res 7(15):1171–1178

    Google Scholar 

  • Hu A, Zuo B, Zhang F, Zhang H, Lan Q (2013) Evaluation of electronspun silk fibroin-based transplants used for facial nerve repair. Otol Neurotol 34(2):311–318

    Article  Google Scholar 

  • Huang W, Begum R, Barber T, Ibba V, Tee NC, Hussain M, Arastoo M, Yang Q, Robson LG, Lesage S, Gheysens T, Skaer NJ, Knight DP, Priestley JV (2012) Regenerative potential of silk conduits in repair of peripheral nerve injury in adult rats. Biomaterials 33(1):59–71

    Article  Google Scholar 

  • Hughes CS, Postovit LM, Lajoie GA (2010) Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10(9):1886–1890

    Article  Google Scholar 

  • Hundepool CA, Nijhuis TH, Kotsougiani D, Friedrich PF, Bishop AT, Shin AY (2017) Optimizing decellularization techniques to create a new nerve allograft: an in vitro study using rodent nerve segments. Neurosurg Focus 42(3):E4

    Article  Google Scholar 

  • Inoue S-i, Tsuda H, Tanaka T, Kobayashi M, Yoshiko M, Magoshi J (2003) Nanostructure of natural fibrous protein: in vitro nanofabric formation of Samia cynthia ricini wild silk fibroin by self-assembling. Nano Lett 3(10):1329–1332

    Article  Google Scholar 

  • Iridag Y, Kazanci M (2006) Preparation and characterization of Bombyx mori silk fibroin and wool keratin. J Appl Polym Sci 100(5):4260–4264

    Article  Google Scholar 

  • Jena K, Pandey JP, Kumari R, Sinha AK, Gupta VP, Singh GP (2018) Tasar silk fiber waste sericin: new source for anti-elastase, anti-tyrosinase and anti-oxidant compounds. Int J Biol Macromol 114:1102–1108

    Article  Google Scholar 

  • Jessen KR, Mirsky R (2016) The repair Schwann cell and its function in regenerating nerves. J Physiol 594(13):3521–3531

    Article  Google Scholar 

  • Jessen KR, Mirsky R, Arthur-Farraj P (2015) The role of cell plasticity in tissue repair: adaptive cellular reprogramming. Dev Cell 34(6):613–620

    Article  Google Scholar 

  • Jiang X, Lim SH, Mao HQ, Chew SY (2010) Current applications and future perspectives of artificial nerve conduits. Exp Neurol 223(1):86–101

    Article  Google Scholar 

  • Johnson EO, Zoubos AB, Soucacos PN (2005) Regeneration and repair of peripheral nerves. Injury 36(Suppl 4):S24–S29

    Article  Google Scholar 

  • Kanno H, Pearse DD, Ozawa H, Itoi E, Bunge MB (2015) Schwann cell transplantation for spinal cord injury repair: its significant therapeutic potential and prospectus. Rev Neurosci 26(2):121–128

    Article  Google Scholar 

  • Knight DP, Vollrath F (2001) Changes in element composition along the spinning duct in a Nephila spider. Naturwissenschaften 88(4):179–182

    Article  Google Scholar 

  • Kornfeld T, Vogt PM, Bucan V, Peck CT, Reimers K, Radtke C (2016) Characterization and schwann cell seeding of up to 15.0 cm long spider silk nerve conduits for reconstruction of peripheral nerve defects. J Funct Biomater 7(4):30

    Article  Google Scholar 

  • Kovoor J (1987) Comparative structure and histochemistry of silk-producing organs in arachnids. In: Nentwig W (ed) Ecophysiology of spiders. Springer, Berlin, Heidelberg, pp 160–186

    Chapter  Google Scholar 

  • Kuhbier JW, Reimers K, Kasper C, Allmeling C, Hillmer A, Menger B, Vogt PM, Radtke C (2011) First investigation of spider silk as a braided microsurgical suture. J Biomed Mater Res B Appl Biomater 97B(2):381–387

    Article  Google Scholar 

  • Kukuruzinska MA, Lennon K (1998) Protein N-glycosylation: molecular genetics and functional significance. Crit Rev Oral Biol Med 9(4):415–448

    Article  Google Scholar 

  • Kundu B, Rajkhowa R, Kundu SC, Wang X (2013) Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev 65(4):457–470

    Article  Google Scholar 

  • Kurioka A, Yamazaki M (2002) Antioxidant in the Cocoon of the silkworm, Bombyx mori. J Insect Biotechnol Sericology 71(3):177–180

    Google Scholar 

  • Lally KP, Cheu HW, Vazquez WD (1993) Prosthetic diaphragm reconstruction in the growing animal. J Pediatr Surg 28(1):45–47

    Article  Google Scholar 

  • Lefevre T, Boudreault S, Cloutier C, Pezolet M (2011) Diversity of molecular transformations involved in the formation of spider silks. J Mol Biol 405(1):238–253

    Article  Google Scholar 

  • Lin YC, Ramadan M, Hronik-Tupaj M, Kaplan DL, Philips BJ, Sivak W, Rubin JP, Marra KG (2011) Spatially controlled delivery of neurotrophic factors in silk fibroin-based nerve conduits for peripheral nerve repair. Ann Plast Surg 67(2):147–155

    Article  Google Scholar 

  • Liu Y, Sponner A, Porter D, Vollrath F (2008) Proline and processing of spider silks. Biomacromolecules 9(1):116–121

    Article  Google Scholar 

  • Lloyd AW (2002) Interfacial bioengineering to enhance surface biocompatibility. Med Device Technol 13(1):18–21

    Google Scholar 

  • Lovett ML, Cannizzaro CM, Vunjak-Novakovic G, Kaplan DL (2008) Gel spinning of silk tubes for tissue engineering. Biomaterials 29(35):4650–4657

    Article  Google Scholar 

  • Madduri S, Papaloizos M, Gander B (2010) Trophically and topographically functionalized silk fibroin nerve conduits for guided peripheral nerve regeneration. Biomaterials 31(8):2323–2334

    Article  Google Scholar 

  • Madsen B, Shao ZZ, Vollrath F (1999) Variability in the mechanical properties of spider silks on three levels: interspecific, intraspecific and intraindividual. Int J Biol Macromol 24(2–3):301–306

    Article  Google Scholar 

  • Magaz A, Faroni A, Gough JE, Reid AJ, Li X, Blaker JJ (2018) Bioactive silk-based nerve guidance conduits for augmenting peripheral nerve repair. Adv Healthc Mater 7(23):e1800308

    Article  Google Scholar 

  • Maksimenko OG, Deykin AV, Khodarovich YM, Georgiev PG (2013) Use of transgenic animals in biotechnology: prospects and problems. Acta Nat 5(1):33–46

    Article  Google Scholar 

  • Mandal BB, Kundu SC (2008) A novel method for dissolution and stabilization of non-mulberry silk gland protein fibroin using anionic surfactant sodium dodecyl sulfate. Biotechnol Bioeng 99(6):1482–1489

    Article  Google Scholar 

  • Mason C, Dunnill P (2008) A brief definition of regenerative medicine. Regen Med 3(1):1–5

    Article  Google Scholar 

  • Matsumoto K, Uejima H, Iwasaki T, Sano Y, Sumino H (1996) Studies on regenerated protein fibers. III. Production of regenerated silk fibroin fiber by the self-dialyzing wet spinning method. J Appl Polym Sci 60(4):503–511

    Article  Google Scholar 

  • Meinel L, Karageorgiou V, Hofmann S, Fajardo R, Snyder B, Li C, Zichner L, Langer R, Vunjak-Novakovic G, Kaplan DL (2004) Engineering bone-like tissue in vitro using human bone marrow stem cells and silk scaffolds. J Biomed Mater Res A 71(1):25–34

    Article  Google Scholar 

  • Melke J, Midha S, Ghosh S, Ito K, Hofmann S (2016) Silk fibroin as biomaterial for bone tissue engineering. Acta Biomater 31:1–16

    Article  Google Scholar 

  • Millesi H, Schmidhammer R (2007) End-to-side coaptation – controversial research issue or important tool in human patients. Acta Neurochir Suppl 100:103–106

    Article  Google Scholar 

  • Min BM, Lee G, Kim SH, Nam YS, Lee TS, Park WH (2004) Electrospinning of silk fibroin nanofibers and its effect on the adhesion and spreading of normal human keratinocytes and fibroblasts in vitro. Biomaterials 25(7–8):1289–1297

    Article  Google Scholar 

  • Mita K, Ichimura S, James TC (1994) Highly repetitive structure and its organization of the silk fibroin gene. J Mol Evol 38(6):583–592

    Article  Google Scholar 

  • Moloney MM, Holbrook LA (1997) Subcellular targeting and purification of recombinant proteins in plant production systems. Biotechnol Genet Eng Rev 14:321–336

    Article  Google Scholar 

  • Mondal M, TrivedyK, Kumar N (2006) The silk proteins, sericin and fibroin in silkworm, Bombyx mori Linn. – a review. J Env Sci 5(2):63–76

    Google Scholar 

  • Moore AM, Kasukurthi R, Magill CK, Farhadi HF, Borschel GH, Mackinnon SE (2009) Limitations of conduits in peripheral nerve repairs. Hand (N Y) 4(2):180–186

    Article  Google Scholar 

  • Moore AM, MacEwan M, Santosa KB, Chenard KE, Ray WZ, Hunter DA, Mackinnon SE, Johnson PJ (2011) Acellular nerve allografts in peripheral nerve regeneration: a comparative study. Muscle Nerve 44(2):221–234

    Article  Google Scholar 

  • Mottaghitalab F, Farokhi M, Zaminy A, Kokabi M, Soleimani M, Mirahmadi F, Shokrgozar MA, Sadeghizadeh M (2013) A biosynthetic nerve guide conduit based on silk/SWNT/fibronectin nanocomposite for peripheral nerve regeneration. PLoS One 8(9):e74417

    Article  Google Scholar 

  • Muheremu A, Ao Q (2015) Past, present, and future of nerve conduits in the treatment of peripheral nerve injury. Biomed Res Int 2015:237507

    Article  Google Scholar 

  • Nazarov R, Jin HJ, Kaplan DL (2004) Porous 3-D scaffolds from regenerated silk fibroin. Biomacromolecules 5(3):718–726

    Article  Google Scholar 

  • Newman J, Newman C (1995) Oh what a tangled web: the medicinal uses of spider silk. Int J Dermatol 34(4):290–292

    Article  Google Scholar 

  • Nichol JW, Khademhosseini A (2009) Modular tissue engineering: engineering biological tissues from the bottom up. Soft Matter 5(7):1312–1319

    Article  Google Scholar 

  • Ovid, Humphries R (1983) Metamorphoses. Indiana University Press, Bloomington

    Google Scholar 

  • Padamwar M, Pawar A (2004) Silk sericin and its applications: a review. J Sci Ind Res 63(4):323–329

    Google Scholar 

  • Patel NP, Lyon KA, Huang JH (2018) An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries. Neural Regen Res 13(5):764–774

    Article  Google Scholar 

  • Pérez-Rigueiro J, Elices M, Llorca J, Viney C (2001) Tensile properties of silkworm silk obtained by forced silking. J Appl Polym Sci 82(8):1928–1935

    Article  Google Scholar 

  • Pérez-Rigueiro J, Elices M, Llorca J, Viney C (2002) Effect of degumming on the tensile properties of silkworm (Bombyx mori) silk fiber. J Appl Polym Sci 84(7):1431–1437

    Article  Google Scholar 

  • Pérez-Rigueiro J, Elices M, Plaza G, Real JI, Guinea GV (2005) The effect of spinning forces on spider silk properties. J Exp Biol 208(14):2633–2639

    Article  Google Scholar 

  • Pfister LA, Papaloizos M, Merkle HP, Gander B (2007) Nerve conduits and growth factor delivery in peripheral nerve repair. J Peripher Nerv Syst 12(2):65–82

    Article  Google Scholar 

  • Putthanarat S, Stribeck N, Fossey SA, Eby RK, Adams WW (2000) Investigation of the nanofibrils of silk fibers. Polymer 41(21):7735–7747

    Article  Google Scholar 

  • Qi Y, Wang H, Wei K, Yang Y, Zheng R-Y, Kim IS, Zhang K-Q (2017) A review of structure construction of silk fibroin biomaterials from single structures to multi-level structures. Int J Mol Sci 18(3):237

    Article  Google Scholar 

  • Qu J, Wang D, Wang H, Dong Y, Zhang F, Zuo B, Zhang H (2013) Electrospun silk fibroin nanofibers in different diameters support neurite outgrowth and promote astrocyte migration. J Biomed Mater Res A 101(9):2667–2678

    Article  Google Scholar 

  • Radtke C (2016) Natural occurring silks and their analogues as materials for nerve conduits. Int J Mol Sci 17(10):1754

    Google Scholar 

  • Radtke C, Allmeling C, Waldmann K-H, Reimers K, Thies K, Schenk HC, Hillmer A, Guggenheim M, Brandes G, Vogt PM (2011) Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep. PLoS One 6(2):e16990

    Article  Google Scholar 

  • Ramshaw JAM, Werkmeister JA, Dumsday GJ (2014) Bioengineered collagens. Bioengineered 5(4):227–233

    Article  Google Scholar 

  • Rao J, Cheng Y, Liu Y, Ye Z, Zhan B, Quan D, Xu Y (2017) A multi-walled silk fibroin/silk sericin nerve conduit coated with poly(lactic-co-glycolic acid) sheath for peripheral nerve regeneration. Mater Sci Eng C Mater Biol Appl 73:319–332

    Article  Google Scholar 

  • Ray WZ, Mackinnon SE (2010) Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy. Exp Neurol 223(1):77–85

    Article  Google Scholar 

  • Rhisiart A a, Vollrath F (1994) Design features of the orb web of the spider, Araneus diadematus. Behav Ecol 5(3):280–287

    Article  Google Scholar 

  • Rising A, Widhe M, Johansson J, Hedhammar M (2011) Spider silk proteins: recent advances in recombinant production, structure-function relationships and biomedical applications. Cell Mol Life Sci 68(2):169–184

    Article  Google Scholar 

  • Rockwood DN, Preda RC, Yucel T, Wang X, Lovett ML, Kaplan DL (2011) Materials fabrication from Bombyx mori silk fibroin. Nat Protoc 6(10):1612–1631

    Article  Google Scholar 

  • Rogers SL, Letourneau PC, Palm SL, McCarthy J, Furcht LT (1983) Neurite extension by peripheral and central nervous system neurons in response to substratum-bound fibronectin and laminin. Dev Biol 98(1):212–220

    Article  Google Scholar 

  • Roloff F, Strauss S, Vogt PM, Bicker G, Radtke C (2014) Spider silk as guiding biomaterial for human model neurons. Biomed Res Int 2014:906819

    Article  Google Scholar 

  • Rosenberg AH, Goldman E, Dunn JJ, Studier FW, Zubay G (1993) Effects of consecutive AGG codons on translation in Escherichia coli, demonstrated with a versatile codon test system. J Bacteriol 175(3):716–722

    Article  Google Scholar 

  • Schafer-Nolte F, Hennecke K, Reimers K, Schnabel R, Allmeling C, Vogt PM, Kuhbier JW, Mirastschijski U (2014) Biomechanics and biocompatibility of woven spider silk meshes during remodeling in a rodent fascia replacement model. Ann Surg 259(4):781–792

    Article  Google Scholar 

  • Scheibel T (2004) Spider silks: recombinant synthesis, assembly, spinning, and engineering of synthetic proteins. Microb Cell Factories 3(1):14

    Article  Google Scholar 

  • Schense JC, Bloch J, Aebischer P, Hubbell JA (2000) Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension. Nat Biotechnol 18(4):415–419

    Article  Google Scholar 

  • Schlosshauer B, Dreesmann L, Schaller HE, Sinis N (2006) Synthetic nerve guide implants in humans: a comprehensive survey. Neurosurgery 59(4):740–747. discussion 747–748

    Article  Google Scholar 

  • Schuh CM, Monforte X, Hackethal J, Redl H, Teuschl AH (2016) Covalent binding of placental derived proteins to silk fibroin improves schwann cell adhesion and proliferation. J Mater Sci Mater Med 27(12):188

    Article  Google Scholar 

  • Seal BL, Otero TC, Panitch A (2001) Polymeric biomaterials for tissue and organ regeneration. Mater Sci Eng R Rep 34(4):147–230

    Article  Google Scholar 

  • Sehnal F, Akai H (1990) Insect silk glands: their types, development and function, and effects of environmental factors and morphogenetic hormones on them. Int J Insect Morphol Embryol 19(2):79–132

    Article  Google Scholar 

  • Silva GA, Czeisler C, Niece KL, Beniash E, Harrington DA, Kessler JA, Stupp SI (2004) Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science 303(5662):1352–1355

    Article  Google Scholar 

  • Sinis N, Schaller HE, Schulte-Eversum C, Schlosshauer B, Doser M, Dietz K, Rosner H, Muller HW, Haerle M (2005) Nerve regeneration across a 2-cm gap in the rat median nerve using a resorbable nerve conduit filled with Schwann cells. J Neurosurg 103(6):1067–1076

    Article  Google Scholar 

  • Soong HK, Kenyon KR (1984) Adverse reactions to virgin silk sutures in cataract surgery. Ophthalmology 91(5):479–483

    Article  Google Scholar 

  • Sorensen HP, Mortensen KK (2005) Advanced genetic strategies for recombinant protein expression in Escherichia coli. J Biotechnol 115(2):113–128

    Article  Google Scholar 

  • Soumya M, Harinatha Reddy A, Nageswari G, Venkatappa B (2017) Silkworm (Bombyx mori) and its constituents: A fascinating insect in science and research. J Entomol Zool Stud 5(5):1701–1705

    Google Scholar 

  • Sponner A, Schlott B, Vollrath F, Unger E, Grosse F, Weisshart K (2005) Characterization of the protein components of Nephila clavipes dragline silk. Biochemistry 44(12):4727–4736

    Article  Google Scholar 

  • Sulaiman OA, Gordon T (2009) Role of chronic Schwann cell denervation in poor functional recovery after nerve injuries and experimental strategies to combat it. Neurosurgery 65(4 Suppl):A105–A114

    Article  Google Scholar 

  • Sun W, Yu H, Shen Y, Banno Y, Xiang Z, Zhang Z (2012) Phylogeny and evolutionary history of the silkworm. Sci China Life Sci 55(6):483–496

    Article  Google Scholar 

  • Sun W, Incitti T, Migliaresi C, Quattrone A, Casarosa S, Motta A (2017a) Viability and neuronal differentiation of neural stem cells encapsulated in silk fibroin hydrogel functionalized with an IKVAV peptide. J Tissue Eng Regen Med 11(5):1532–1541

    Google Scholar 

  • Sun B, Zhou Z, Wu T, Chen W, Li D, Zheng H, El-Hamshary H, Al-Deyab SS, Mo X, Yu Y (2017b) Development of nanofiber sponges-containing nerve guidance conduit for peripheral nerve regeneration in vivo. ACS Appl Mater Interfaces 9(32):26684–26696

    Google Scholar 

  • Sutherland TD, Young JH, Weisman S, Hayashi CY, Merritt DJ (2010) Insect silk: one name, many materials. Annu Rev Entomol 55(1):171–188

    Article  Google Scholar 

  • Tang X, Ding F, Yang Y, Hu N, Wu H, Gu X (2009) Evaluation on in vitro biocompatibility of silk fibroin-based biomaterials with primarily cultured hippocampal neurons. J Biomed Mater Res A 91(1):166–174

    Article  Google Scholar 

  • Teh TKH, Toh S-L, Goh JCH (2010) Optimization of the silk scaffold sericin removal process for retention of silk fibroin protein structure and mechanical properties. Biomed Mater 5(3):035008

    Article  Google Scholar 

  • Teuschl AH, Schuh C, Halbweis R, Pajer K, Marton G, Hopf R, Mosia S, Runzler D, Redl H, Nogradi A, Hausner T (2015) A new preparation method for anisotropic silk fibroin nerve guidance conduits and its evaluation in vitro and in a rat sciatic nerve defect model. Tissue Eng Part C Methods 21(9):945–957

    Article  Google Scholar 

  • Thiel BL, Guess KB, Viney C (1997) Non-periodic lattice crystals in the hierarchical microstructure of spider (major ampullate) silk. Biopolymers 41(7):703–719

    Article  Google Scholar 

  • Tokareva O, Jacobsen M, Buehler M, Wong J, Kaplan DL (2014) Structure-function-property-design interplay in biopolymers: spider silk. Acta Biomater 10(4):1612–1626

    Article  Google Scholar 

  • Uebersax L, Mattotti M, Papaloizos M, Merkle HP, Gander B, Meinel L (2007) Silk fibroin matrices for the controlled release of nerve growth factor (NGF). Biomaterials 28(30):4449–4460

    Article  Google Scholar 

  • Unger RE, Wolf M, Peters K, Motta A, Migliaresi C, James Kirkpatrick C (2004) Growth of human cells on a non-woven silk fibroin net: a potential for use in tissue engineering. Biomaterials 25(6):1069–1075

    Article  Google Scholar 

  • Vepari C, Kaplan DL (2007) Silk as a biomaterial. Prog Polym Sci 32(8–9):991–1007

    Article  Google Scholar 

  • Verdu E, Labrador RO, Rodriguez FJ, Ceballos D, Fores J, Navarro X (2002) Alignment of collagen and laminin-containing gels improve nerve regeneration within silicone tubes. Restor Neurol Neurosci 20(5):169–179

    Google Scholar 

  • Vleggeert-Lankamp CL, Pego AP, Lakke EA, Deenen M, Marani E, Thomeer RT (2004) Adhesion and proliferation of human Schwann cells on adhesive coatings. Biomaterials 25(14):2741–2751

    Article  Google Scholar 

  • Vollrath F (1992) Spider webs and silks. Sci Am 266(3):70–77

    Article  MathSciNet  Google Scholar 

  • Vollrath F (1993) General properties of some spider silks. In: Silk polymers, American chemical society symposium series 544, Washington, DC, pp 17–28

    Google Scholar 

  • Vollrath F (2000) Strength and structure of spiders’ silks. J Biotechnol 74(2):67–83

    Google Scholar 

  • Vollrath F (2005) Spiders' webs. Curr Biol 15(10):R364–R365

    Article  Google Scholar 

  • Vollrath F, Porter D (2006) Spider silk as archetypal protein elastomer. Soft Matter 2(5):377–385

    Article  Google Scholar 

  • Wang HB, Mullins ME, Cregg JM, McCarthy CW, Gilbert RJ (2010) Varying the diameter of aligned electrospun fibers alters neurite outgrowth and Schwann cell migration. Acta Biomater 6(8):2970–2978

    Article  Google Scholar 

  • Wang C, Jia Y, Yang W, Zhang C, Zhang K, Chai Y (2018) Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits. J Biomed Mater Res A 106(7):2070–2077

    Article  Google Scholar 

  • Wen H, Lan X, Zhang Y, Zhao T, Wang Y, Kajiura Z, Nakagaki M (2010) Transgenic silkworms (Bombyx mori) produce recombinant spider dragline silk in cocoons. Mol Biol Rep 37(4):1815–1821

    Article  Google Scholar 

  • Whitlock EL, Tuffaha SH, Luciano JP, Yan Y, Hunter DA, Magill CK, Moore AM, Tong AY, Mackinnon SE, Borschel GH (2009) Processed allografts and type I collagen conduits for repair of peripheral nerve gaps. Muscle Nerve 39(6):787–799

    Article  Google Scholar 

  • Widhe M, Johansson U, Hillerdahl CO, Hedhammar M (2013) Recombinant spider silk with cell binding motifs for specific adherence of cells. Biomaterials 34(33):8223–8234

    Article  Google Scholar 

  • Work RW (1976) The force-elongation behavior of web fibers and silks forcibly obtained from orb-web-spinning spiders. Text Res J 46(7):485–492

    Article  Google Scholar 

  • Wu HC, Quan DN, Tsao CY, Liu Y, Terrell JL, Luo X, Yang JC, Payne GF, Bentley WE (2017) Conferring biological activity to native spider silk: a biofunctionalized protein-based microfiber. Biotechnol Bioeng 114(1):83–95

    Article  Google Scholar 

  • Xia X-X, Qian Z-G, Ki CS, Park YH, Kaplan DL, Lee SY (2010) Native-sized recombinant spider silk protein produced in metabolically engineered Escherichia coli results in a strong fiber. Proc Natl Acad Sci 107(32):14059–14063

    Article  Google Scholar 

  • Xia Q, Li S, Feng Q (2014) Advances in silkworm studies accelerated by the genome sequencing of Bombyx mori. Annu Rev Entomol 59(1):513–536

    Article  Google Scholar 

  • Xie F, Zhang H, Shao H, Hu X (2006) Effect of shearing on formation of silk fibers from regenerated Bombyx mori silk fibroin aqueous solution. Int J Biol Macromol 38(3–5):284–288

    Article  Google Scholar 

  • Xie S, Lu F, Han J, Tao K, Wang H, Simental A, Hu D, Yang H (2017) Efficient generation of functional Schwann cells from adipose-derived stem cells in defined conditions. Cell Cycle 16(9):841–851

    Article  Google Scholar 

  • Xu H-T, Fan B-L, Yu S-Y, Huang Y-H, Zhao Z-H, Lian Z-X, Dai Y-P, Wang L-L, Liu Z-L, Fei J, Li N (2007) Construct synthetic gene encoding artificial spider dragline silk protein and its expression in Milk of transgenic mice. Anim Biotechnol 18(1):1–12

    Article  Google Scholar 

  • Xu J, Dong Q, Yu Y, Niu B, Ji D, Li M, Huang Y, Chen X, Tan A (2018) Mass spider silk production through targeted gene replacement in Bombyx mori. Proc Natl Acad Sci 115(35):8757–8762

    Article  Google Scholar 

  • Xue C, Zhu H, Tan D, Ren H, Gu X, Zhao Y, Zhang P, Sun Z, Yang Y, Gu J, Gu Y, Gu X (2018) Electrospun silk fibroin-based neural scaffold for bridging a long sciatic nerve gap in dogs. J Tissue Eng Regen Med 12(2):e1143–e1153

    Article  Google Scholar 

  • Yang Y, Shao Z, Chen X, Zhou P (2004) Optical spectroscopy to investigate the structure of regenerated Bombyx mori silk fibroin in solution. Biomacromolecules 5(3):773–779

    Article  Google Scholar 

  • Yang Y, Chen X, Ding F, Zhang P, Liu J, Gu X (2007a) Biocompatibility evaluation of silk fibroin with peripheral nerve tissues and cells in vitro. Biomaterials 28(9):1643–1652

    Google Scholar 

  • Yang Y, Ding F, Wu J, Hu W, Liu W, Liu J, Gu X (2007b) Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials 28(36):5526–5535

    Google Scholar 

  • Yang Y, Yuan X, Ding F, Yao D, Gu Y, Liu J, Gu X (2011) Repair of rat sciatic nerve gap by a silk fibroin-based scaffold added with bone marrow mesenchymal stem cells. Tissue Eng Part A 17(17–18):2231–2244

    Article  Google Scholar 

  • Yip EC, Rayor LS (2014) Maternal care and subsocial behaviour in spiders. Biol Rev 89(2):427–449

    Article  Google Scholar 

  • Yoo HS, Kim TG, Park TG (2009) Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. Adv Drug Deliv Rev 61(12):1033–1042

    Article  Google Scholar 

  • Zarkoob S, Eby RK, Reneker DH, Hudson SD, Ertley D, Adams WW (2004) Structure and morphology of electrospun silk nanofibers. Polymer 45(11):3973–3977

    Article  Google Scholar 

  • Zeplin PH, Maksimovikj NC, Jordan MC, Nickel J, Lang G, Leimer AH, Römer L, Scheibel T (2014) Spider silk coatings as a bioshield to reduce Periprosthetic fibrous capsule formation. Adv Funct Mater 24(18):2658–2666

    Article  Google Scholar 

  • Zhang Y-Q (2002) Applications of natural silk protein sericin in biomaterials. Biotechnol Adv 20(2):91–100

    Article  Google Scholar 

  • Zhang X, Reagan MR, Kaplan DL (2009) Electrospun silk biomaterial scaffolds for regenerative medicine. Adv Drug Deliv Rev 61(12):988–1006

    Article  Google Scholar 

  • Zhang Q, Zhao Y, Yan S, Yang Y, Zhao H, Li M, Lu S, Kaplan DL (2012) Preparation of uniaxial multichannel silk fibroin scaffolds for guiding primary neurons. Acta Biomater 8(7):2628–2638

    Article  Google Scholar 

  • Zhu C, Huang J, Xue C, Wang Y, Wang S, Bao S, Chen R, Li Y, Gu Y (2018) Skin derived precursor Schwann cell-generated acellular matrix modified chitosan/silk scaffolds for bridging rat sciatic nerve gap. Neurosci Res 135:21–31

    Article  Google Scholar 

  • Zuo B, Dai L, Wu Z (2006) Analysis of structure and properties of biodegradable regenerated silk fibroin fibers. J Mater Sci 41(11):3357–3361

    Article  Google Scholar 

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Millesi, F., Weiss, T., Radtke, C. (2022). Silk Biomaterials in Peripheral Nerve Tissue Engineering. In: Phillips, J.B., Hercher, D., Hausner, T. (eds) Peripheral Nerve Tissue Engineering and Regeneration. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-030-21052-6_5

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