Multichannel silk protein/laminin grafts for spinal cord injury repair
Qiang Zhang
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
School of Textile Science and Engineering, Wuhan Textile University, Wuhan, 430073 China
Department of Biomedical Engineering, Tufts University, Medford, 02155 Massachusetts
These authors contributed equally to this work.
Search for more papers by this authorShuqin Yan
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
School of Textile Science and Engineering, Wuhan Textile University, Wuhan, 430073 China
These authors contributed equally to this work.
Search for more papers by this authorRenchuan You
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
School of Textile Science and Engineering, Wuhan Textile University, Wuhan, 430073 China
Search for more papers by this authorDavid L. Kaplan
Department of Biomedical Engineering, Tufts University, Medford, 02155 Massachusetts
Search for more papers by this authorYu Liu
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Search for more papers by this authorJing Qu
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Search for more papers by this authorXiufang Li
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Search for more papers by this authorCorresponding Author
Mingzhong Li
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Correspondence to: M. Li; e-mail: [email protected]Search for more papers by this authorXin Wang
Centre for Advanced Materials and Performance Textiles, School of Fashion and Textiles, RMIT University, Melbourne, 3056 Victoria, Australia
Search for more papers by this authorQiang Zhang
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
School of Textile Science and Engineering, Wuhan Textile University, Wuhan, 430073 China
Department of Biomedical Engineering, Tufts University, Medford, 02155 Massachusetts
These authors contributed equally to this work.
Search for more papers by this authorShuqin Yan
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
School of Textile Science and Engineering, Wuhan Textile University, Wuhan, 430073 China
These authors contributed equally to this work.
Search for more papers by this authorRenchuan You
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
School of Textile Science and Engineering, Wuhan Textile University, Wuhan, 430073 China
Search for more papers by this authorDavid L. Kaplan
Department of Biomedical Engineering, Tufts University, Medford, 02155 Massachusetts
Search for more papers by this authorYu Liu
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Search for more papers by this authorJing Qu
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Search for more papers by this authorXiufang Li
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Search for more papers by this authorCorresponding Author
Mingzhong Li
National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123 China
Correspondence to: M. Li; e-mail: [email protected]Search for more papers by this authorXin Wang
Centre for Advanced Materials and Performance Textiles, School of Fashion and Textiles, RMIT University, Melbourne, 3056 Victoria, Australia
Search for more papers by this authorAbstract
The physical, chemical, and bioactive cues provided by biomaterials are critical for spinal cord regeneration following injury. In this study, we investigated the bioactivity of a silk-based scaffold for nerve tissue remodeling that featured morphological guidance in the form of ridges as well as bioactive molecules. Multichannel/laminin (LN) silk scaffolds stimulated growth, development, and the extension of primary hippocampal neurons after 7 days of culture in vitro. And then, the multichannel/LN silk scaffolds were implanted into 2-mm-long hemisection defects in Sprague-Dawley rat spinal cords for 70 days to evaluate their bioactivities of spinal cord remolding. Our results demonstrated that animal behavior was significantly improved in the multichannel/LN group, as evaluated by Basso–Beattie–Bresnahan score, whereas the implantation of multichannels and random pores groups resulted in recurring limps. Moreover, histology and immunohistochemical staining revealed an increase in blood vessels and expression of growth associated protein-43 and neurofilament-200 as well as reduced expression of glial fibrillary acidic protein in the multichannel/LN group, which contributed to the rebuilding of spinal cord defects. Thus, multichannel/LN silk scaffolds mediated cell migration, stimulated blood capillary formation, and promoted axonal extension, suggesting the utility of these scaffolds for spinal cord reconstruction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3045–3057, 2016.
REFERENCES
- 1 Burnside ER, Bradbury EJ. Manipulating the extracellular matrix and its role in brain and spinal cord plasticity and repair. Neuropath Appl Neuro 2014; 40: 26–59.
- 2 Teng YD, Lavik EB, Qu XL, Park KI, Ourednik J, Zurakowski DE, Langer R, Snyder EY. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci USA 2002; 99: 3024–3029.
- 3 Stokols S, Tuszynski MH. Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear axonal growth following spinal cord injury. Biomaterials 2006; 27: 443–451.
- 4 Wang CY, Zhang KH, Fan CY, Mo XM, Ruan HJ, Li FF. Aligned natural-synthetic polyblend nanofibers for peripheral nerve regeneration. Acta Biomater 2011; 7: 634–643.
- 5 Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull 1999; 49: 377–391.
- 6 Schimchowitsch S, Cassel JC. Polyamine and aminoguanidine treatments to promote structural and functional recovery in the adult mammalian brain after injury: A brief literature review and preliminary data about their combined administration. J Physiol Paris 2006; 99: 221–223.
- 7 Papenburg BJ, Vogelaar L, Bolhuis-Versteeg LAM, Lammertink RGH, Stamatialis D, Wessling M. One-step fabrication of porous micropatterned scaffolds to control cell behavior. Biomaterials 2007; 28: 1998–2009.
- 8 Li H, Koenig AM, Sloan P, Leipzig ND. In vivo assessment of guided neural stem cell differentiation in growth factor immobilized chitosan-based hydrogel scaffolds. Biomaterials 2014; 35: 9049–9057.
- 9 King VR, Henseler M, Brown RA, Priestley JV. Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat. Exp Neurol 2003; 182: 383–398.
- 10 Wang G, Ao Q, Gong K, Wang AJ, Zheng L, Gong Y, Zhang X. The effect of topology of chitosan biomaterials on the differentiation and proliferation of neural stem cells. Acta Biomater 2010; 6: 3630–3639.
- 11 Khademhosseini A, Langer R, Borenstein J, Vacanti JP. Microscale technologies for tissue engineering and biology. Proc Natl Acad Sci USA 2006; 103: 2480–2487.
- 12 Führmann T, Hillen LM, Montzka K, Wöltje M, Brook GA. Cell-cell interactions of human neural progenitor-derived astrocytes within a microstructured 3D-scaffold. Biomaterials 2010; 31: 7705–7715.
- 13 Moore MJ, Friedman JA, Lewellyn EB, Mantila SM, Krych AJ, Ameenuddin S, Knight AM, Lu L, Currier BL, Spinner RJ, Marsh RW, Windebank AJ, Yaszemski MJ. Multiple-channel scaffolds to promote spinal cord axon regeneration. Biomaterials 2006; 27: 419–429.
- 14 Tejeda-Montes E, Smith KH, Poch M, López-Bosque MJ, Martín L, Alonso M, Engel E, Mata A. Engineering membrane scaffolds with both physical and biomolecular signaling. Acta Biomater 2012; 8: 998–1009.
- 15 Hollister SJ. Porous scaffold design for tissue engineering. Nat Mater 2005; 4: 518–524.
- 16 Stokols S, Tuszynski MH. The fabrication and characterization of linearly oriented nerve guidance scaffolds for spinal cord injury. Biomaterials 2004; 25: 5839–5846.
- 17 Zhang Q, Zhao Y, Yan S, Yang Y, Zhao H, Li M, Lu S, Kaplan DL. Preparation of uniaxial multichannel silk fibroin scaffolds for guiding primary neurons. Acta Biomater 2012; 8: 2628–2638.
- 18 Du R, Wang Y, Teng JF, Lu H, Lu R, Shi Z. Effect of integrin combined laminin on peripheral blood vessel of cerebral infarction and endogenous nerve regeneration. J Biol Regul Homeost Agents 2015; 29: 167–174.
- 19 Yurchenco PD, Patton BL. Developmental and pathogenic mechanisms of basement membrane assembly. Curr Pharm Des 2009; 15: 1277–1294.
- 20 Gumbiner BM. Cell adhesion: Review the molecular basis of tissue architecture and morphogenesis. Cell 1996; 84: 345–357.
- 21 Zeck G, Fromherz P. Repulsion and attraction by extracellular matrix protein in cell adhesion studied with nerve cells and lipid vesicles on silicon chips. Langmuir 2003; 19: 1580–1585.
- 22 Cheng H, Huang YC, Chang PT, Huang YY. Laminin-incorporated nerve conduits made by plasma treatment for repairing spinal cord injury. Biochem Biophys Res Commun 2007; 357: 938–944.
- 23 Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG, Quaranta V. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 1997; 277: 225–228.
- 24 Ji K, Tsirka SE. Inflammation modulates expression of laminin in the central nervous system following ischemic injury. J Neuroinflamm 2012; 9: 1–12.
- 25 Moy RL, Lee A, Zalka A. Commonly used suture materials in skin surgery. Am Fam Physician 1991; 44: 2123–2128.
- 26 Minoura N, Aiba S, Gotoh Y, Tsukada M, Imai Y. Attachment and growth of cultured fibroblast cells on silk protein matrices. J Biomed Mater Res 1995; 29: 1215–1221.
- 27 Zhang W, Wray L, Rnjak-Kovacina J, Xu L, Zou D, Wang S, Zhang M, Dong J, Li G, Kaplan DL, Jiang X. Vascularization of hollow channel-modified porous silk scaffolds with endothelial cells for tissue regeneration. Biomaterials 2015; 56: 68–77.
- 28 Li C, Luo T, Zheng Z, Murphy AR, Wang X, Kaplan DL. Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells. Acta Biomater 2015; 11: 222–232.
- 29 Lu Q, Hu X, Wang XQ, Kluge JA, Lu SZ, Cebe P, Kaplan DL. Water-insoluble silk films with silk I structure. Acta Biomater 2010; 6: 1380–1387.
- 30 Zhang Q, Yan S, Li M. Silk fibroin based porous materials. Materials 2009; 2: 2276–2295.
- 31 Hopkins AM, Laporte LD, Tortelli F, Spedden E, Staii C, Atherton TJ, Hubbell JA, Kaplan DL. Silk hydrogels as soft substrates for neural tissue engineering. Adv Funct Mater 2013; 23: 5140–5149.
- 32 Schneider A, Wang XY, Kaplan DL, Garlick JA, Egles C. Biofunctionalized electrospun silk mats as a topical bioactive dressing for accelerated wound healing. Acta Biomater 2009; 5: 2570–2578.
- 33 Yang YM, Chen XM, Ding F, Zhang P, Liu J, Gu XS. Biocompatibility evaluation of silk fibroin with peripheral nerve tissues and cells in vitro. Biomaterials 2007; 28: 1643–1652.
- 34 Yang YM, Ding F, Wu J, Hu W, Liu W, Liu J, Gu X. Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials 2007; 28: 5526–5535.
- 35 Tang X, Ding F, Yang YM, Hu N, Wu H, Gu XS. Evaluation on in vitro biocompatibility of silk fibroin-based biomaterials with primarily cultured hippocampal neurons. J Biomed Mater Res A 2009; 91: 166–174.
- 36 Shi S, Jan L, Jan Y. Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 2003; 112: 63–75.
- 37 Jiang H, Guo W, Liang X, Rao Y. Both the establishment and the maintenance of neuronal polarity require active mechanisms: Critical roles of GSK-3b and its upstream regulators. Cell 2005; 120: 123–135.
- 38 Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995; 12: 1–21.
- 39 Yan S, Zhang Q, Wang J, Liu Y, Lu S, Li M, Kaplan DL. Silk fibroin/chondroitin sulfate/hyaluronic acid ternary scaffolds for dermal tissue reconstruction. Acta Biomater 2013; 9: 6771–6782.
- 40 Eisenmann H, Letsiou I, Feuchtinger A, Beisker W, Mannweiler E, Hutzler P, Arnz P. Interception of small particles by flocculent structures, sessile ciliates, and the basic layer of a waste water biofilm. Appl Environ Microbiol 2001; 67: 4286–4292.
- 41 Iwasaki M, Wilcox JT, Nishimura Y, Zweckberger K, Suzuki H, Wang J, et al. Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury. Biomaterials 2014; 35: 2617–2629.
- 42 Rochkind S, Shahar A, Fliss D, El-Ani D, Astachov L, Hayon T, Alon M, Zamostiano R, Ayalon O, Biton IE, Cohen Y, Halperin R, Schneider D, Oron A, Nevo Z. Development of a tissue-engineered composite implant for treating traumatic paraplegia in rats. Eur Spine J 2006; 15: 234–245.
- 43 Han Q, Jin W, Xiao Z, Ni H, Wang J, Kong J, Wu J, Liang W, Chen L, Zhao Y, Chen B, Dai J. The promotion of neural regeneration in an extreme rat spinal cord injury model using a collagen scaffold containing a collagen binding neuroprotective protein and an EGFR neutralizing antibody. Biomaterials 2010; 31: 9212–9220.
- 44 Wang S, Ghezzi CE, White JD, Kaplan DL. Coculture of dorsal root ganglion neurons and differentiated human corneal stromal stem cells on silk-based scaffolds. J Biomed Mater Res A 2015; 103: 3339–3348.
- 45 Zhao Y, Zhao W, Yu S, Guo Y, Gu X, Yang Y. Biocompatibility evaluation of electrospun silk fibroin nanofibrous mats with primarily cultured rat hippocampal neurons. Biomed Mater Eng 2013; 23: 545–554.
- 46 Gu Y, Zhu J, Xue C, Li Z, Ding F, Yang Y, Gu X. Chitosan/silk fibroin-based, Schwann cell-derived extracellular matrix-modified scaffolds for bridging rat sciatic nerve gaps. Biomaterials 2014; 35: 2253–22563.
- 47 Yang Y, Yuan X, Ding F, Yao D, Gu Y, Liu J, Gu X. Repair of rat sciatic nerve gap by a silk fibroin-based scaffold added with bone marrow mesenchymal stem cells. Tissue Eng Part A 2011; 17: 2231–2244.
- 48 Park SY, Ki CS, Park YH, Lee KG, Kang SW, Kweon HY, Kim HJ. Functional recovery guided by an electrospun silk fibroin conduit after sciatic nerve injury in rats. J Tissue Eng Regen Med 2015; 9: 66–76.
- 49 Gao M, Lu P, Bednark B, Lynam D, Conner JM, Sakamoto J, Tuszynski MH. Templated agarose scaffolds for the support of motor axon regeneration into sites of complete spinal cord transection. Biomaterials 2013; 34: 1529–1536.
- 50 Hsu SH, Kuo WC, Chen YT, Yen CT, Chen YF, Chen KS, Huang WC, Cheng H. New nerve regeneration strategy combining laminin-coated chitosan conduits and stem cell therapy. Acta Biomater 2013; 9: 6606–6615.
- 51 Yu WM, Yu H, Chen ZL, Strickland S. Disruption of laminin in the peripheral nervous system impedes nonmyelinating Schwann cell development and impairs nociceptive sensory function. Glia 2009; 57: 850–859.
- 52 Sun W, Sun C, Zhao H, Lin H, Han Q, Wang J, Ma H, Chen B, Xiao Z, Dai J. Improvement of sciatic nerve regeneration using laminin-binding human NGF-b. PLoS One 2009; 4: e6180.
- 53 Papa S, Rossi F, Ferrari R, Mariani A, De Paola M, Caron I, Fiordaliso F, Bisighini C, Sammali E, Colombo C, Gobbi M, Canovi M, Lucchetti J, Peviani M, Morbidelli M, Forloni G, Perale G, Moscatelli D, Veglianese P. Selective nanovector mediated treatment of activated proinflammatory microglia/macrophages in spinal cord injury. ACS Nano 2013; 7: 9881–9895.
- 54 Mahoney MJ, Chen RR, Tan J, Mark Saltzman W. The influence of microchannels on neurite growth and architecture. Biomaterials 2005; 26: 771–778.
- 55 Courel MN, Girard N, Delpech B, Chauzy C. Specific monoclonal antibodies to glial fibrillary acidic protein (GFAP). J Neuroimmunol 1986; 11: 271–276.
- 56 Fitch MT, Silver J. CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp Neurol 2008; 209: 294–301.
- 57 Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O, Schwab ME. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci 2004; 7: 269–77.
- 58 Mills CD. M1 and M2 macrophages: Oracles of health and disease. Crit Rev Immunol 2012; 32: 463–488.
- 59 Zhang X, Baughman CB, Kaplan DL. In vitro evaluation of electrospun silk fibroin scaffolds for vascular cell growth. Biomaterials 2008; 29: 2217–2227.
- 60 Li Y, Field PM, Raisman G. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 1997; 26: 2000–2002.
- 61 Temple S. The development of neural stem cells. Nature 2001; 414: 112–117.
- 62 Shao Z, Browning JL, Lee X, Scott ML, Shulga-Morskaya S, Allaire N, Thill G, Levesque M, Sah D, McCoy JM, Murray B, Jung V, Pepinsky RB, Mi S. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 2005; 45: 353–359.