Spider Silk for Tissue Engineering Applications

Due to its properties, such as biodegradability, low density, excellent biocompatibility and unique mechanics, spider silk has been used as a natural biomaterial for a myriad of applications. First clinical applications of spider silk as suture material go back to the 18th century. Nowadays, since natural production using spiders is limited due to problems with farming spiders, recombinant production of spider silk proteins seems to be the best way to produce material in sufficient quantities. The availability of recombinantly produced spider silk proteins, as well as their good processability has opened the path towards modern biomedical applications. Here, we highlight the research on spider silk-based materials in the field of tissue engineering and summarize various two-dimensional (2D) and three-dimensional (3D) scaffolds made of spider silk. Finally, different applications of spider silk-based materials are reviewed in the field of tissue engineering in vitro and in vivo.

[1]  A. Arkudas,et al.  Intrinsic Vascularization of Recombinant eADF4(C16) Spider Silk Matrices in the Arteriovenous Loop Model. , 2019, Tissue engineering. Part A.

[2]  G. Lubec,et al.  Spider silk proteome provides insight into the structural characterization of Nephila clavipes flagelliform spidroin , 2018, Scientific Reports.

[3]  T. Scheibel,et al.  Recombinant production of spider silk proteins. , 2013, Advances in applied microbiology.

[4]  Hojjat Naderi,et al.  Review paper: Critical Issues in Tissue Engineering: Biomaterials, Cell Sources, Angiogenesis, and Drug Delivery Systems , 2011, Journal of biomaterials applications.

[5]  J. Johansson,et al.  Spider silk for xeno-free long-term self-renewal and differentiation of human pluripotent stem cells. , 2014, Biomaterials.

[6]  P. Vogt,et al.  Artificial Skin – Culturing of Different Skin Cell Lines for Generating an Artificial Skin Substitute on Cross-Weaved Spider Silk Fibres , 2011, PloS one.

[7]  P. Vogt,et al.  Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep , 2011, PloS one.

[8]  A. Osbourn,et al.  Capillary-induced contact guidance. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[9]  Germán L. Rosano,et al.  Recombinant protein expression in Escherichia coli: advances and challenges , 2014, Front. Microbiol..

[10]  S. Gorb,et al.  An engineered spider silk protein forms microspheres. , 2008, Angewandte Chemie.

[11]  Thomas H. Clarke,et al.  Genomic perspectives of spider silk genes through target capture sequencing: Conservation of stabilization mechanisms and homology-based structural models of spidroin terminal regions. , 2018, International journal of biological macromolecules.

[12]  T. Scheibel,et al.  Biofabrication of cell-loaded 3D spider silk constructs. , 2015, Angewandte Chemie.

[13]  Peter M Vogt,et al.  Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit , 2006, Journal of cellular and molecular medicine.

[14]  P. Vogt,et al.  Bundles of Spider Silk, Braided into Sutures, Resist Basic Cyclic Tests: Potential Use for Flexor Tendon Repair , 2013, PloS one.

[15]  David L Kaplan,et al.  Silk as a Biomaterial. , 2007, Progress in polymer science.

[16]  A. O’Connor,et al.  Nerve guidance conduit design based on self-rolling tubes , 2020, Materials today. Bio.

[17]  A. Khademhosseini,et al.  Modular Tissue Engineering: Engineering Biological Tissues from the Bottom Up. , 2009, Soft matter.

[18]  R. Lewis,et al.  COMPARISON OF PHYSICAL PROPERTIES OF THREE SILKS FROM NEPHILA CLA VIPES AND ARANEUS GEMMOIDES , 2016 .

[19]  F. Kremer,et al.  Impact of initial solvent on thermal stability and mechanical properties of recombinant spider silk films , 2011 .

[20]  P. Vogt,et al.  Spider Silk as Guiding Biomaterial for Human Model Neurons , 2014, BioMed research international.

[21]  T. Scheibel,et al.  Recombinant Spider Silk and Collagen-Based Nerve Guidance Conduits Support Neuronal Cell Differentiation and Functionality in Vitro. , 2019, ACS applied bio materials.

[22]  M. Hedhammar,et al.  Silkworm Silk Matrices Coated with Functionalized Spider Silk Accelerate Healing of Diabetic Wounds. , 2019, ACS biomaterials science & engineering.

[23]  Thomas Scheibel,et al.  Recombinant Spider Silks—Biopolymers with Potential for Future Applications , 2011 .

[24]  Andrew M. Smith,et al.  Decoding the secrets of spider silk , 2011 .

[25]  M. Hedhammar,et al.  A fibronectin mimetic motif improves integrin mediated cell biding to recombinant spider silk matrices. , 2016, Biomaterials.

[26]  Jenna Sutton Hanging by a Thread , 2018 .

[27]  David L Kaplan,et al.  Silk-based biomaterials. , 2003, Biomaterials.

[28]  M. Denny,et al.  The structure and properties of spider silk , 1986 .

[29]  S. Wohlrab,et al.  Surface Modification of Polymeric Biomaterials Using Recombinant Spider Silk Proteins. , 2017, ACS biomaterials science & engineering.

[30]  J. Hardy,et al.  Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering , 2016, Materials.

[31]  L. Griffith,et al.  Tissue Engineering--Current Challenges and Expanding Opportunities , 2002, Science.

[32]  Marion Ghibaudo,et al.  Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates , 2007, Proceedings of the National Academy of Sciences.

[33]  C. Mason,et al.  A brief definition of regenerative medicine. , 2008, Regenerative medicine.

[34]  Ricki Lewis Unraveling the weave of spider silk One of nature's wondrous chemical structures is being dissected so that it can be used in human inventions , 1996 .

[35]  J. Scheller,et al.  Purification of Spider Silk-elastin from Transgenic Plants and Application for Human Chondrocyte Proliferation , 2004, Transgenic Research.

[36]  M. Kuntner,et al.  The transcriptome of Darwin’s bark spider silk glands predicts proteins contributing to dragline silk toughness , 2019, Communications Biology.

[37]  J. Newman,et al.  OH WHAT A TANGLED WEB: THE MEDICINAL USES OE SPIDER SILK , 1995, International Journal of Dermatology.

[38]  D. Kaplan,et al.  Osteoinductive recombinant silk fusion proteins for bone regeneration. , 2017, Acta Biomaterialia.

[39]  T. Scheibel,et al.  Biomedical Applications of Recombinant Silk‐Based Materials , 2018, Advanced materials.

[40]  Lu Baoyong,et al.  Evaluation of a new type of wound dressing made from recombinant spider silk protein using rat models. , 2010, Burns : journal of the International Society for Burn Injuries.

[41]  M. Hedhammar,et al.  Recombinant spider silk with cell binding motifs for specific adherence of cells. , 2013, Biomaterials.

[42]  T. Scheibel,et al.  To spin or not to spin: spider silk fibers and more , 2015, Applied Microbiology and Biotechnology.

[43]  Min Li,et al.  A Novel Scaffold from Recombinant Spider Silk Protein in Tissue Engineering , 2010 .

[44]  T. Scheibel,et al.  Novel Assembly Properties of Recombinant Spider Dragline Silk Proteins , 2004, Current Biology.

[45]  Sumner N. Levine,et al.  Materials for Biomedical Engineering , 1968 .

[46]  David L. Kaplan,et al.  Spider silk-bone sialoprotein fusion proteins for bone tissue engineering , 2011 .

[47]  T. Scheibel,et al.  Applicability of biotechnologically produced insect silks , 2017, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[48]  Thomas Scheibel,et al.  Spider Silk Coatings as a Bioshield to Reduce Periprosthetic Fibrous Capsule Formation , 2014 .

[49]  Likai Li,et al.  Black phosphorus field-effect transistors. , 2014, Nature nanotechnology.

[50]  Lukas Eisoldt Funktion und Einfluss der nicht-repetitiven, terminalen Domänen auf Speicherung und Assemblierung von Spinnenseidenproteinen , 2013 .

[51]  M. Hedhammar,et al.  Tissue Response to Subcutaneously Implanted Recombinant Spider Silk: An in Vivo Study , 2009, Materials.

[52]  T. Scheibel,et al.  Surface Features of Recombinant Spider Silk Protein eADF4(κ16)‐Made Materials are Well‐Suited for Cardiac Tissue Engineering , 2017 .

[53]  T. Scheibel,et al.  Foams Made of Engineered Recombinant Spider Silk Proteins as 3D Scaffolds for Cell Growth. , 2016, ACS biomaterials science & engineering.

[54]  T. Scheibel,et al.  Aqueous electrospinning of recombinant spider silk proteins. , 2020, Materials science & engineering. C, Materials for biological applications.

[55]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[56]  M. Hedhammar,et al.  Recombinant Spider Silk Functionalized Silkworm Silk Matrices as Potential Bioactive Wound Dressings and Skin Grafts. , 2018, ACS applied materials & interfaces.

[57]  A. Terzic,et al.  Two-Dimensional Black Phosphorus and Graphene Oxide Nanosheets Synergistically Enhance Cell Proliferation and Osteogenesis on 3D Printed Scaffolds. , 2019, ACS applied materials & interfaces.

[58]  Thomas Scheibel,et al.  Biotechnological production of spider-silk proteins enables new applications. , 2007, Macromolecular bioscience.

[59]  T. Scheibel,et al.  Enzymatic Degradation of Films, Particles, and Nonwoven Meshes Made of a Recombinant Spider Silk Protein. , 2015, ACS biomaterials science & engineering.

[60]  S. Geimer,et al.  Interactions of Fibroblasts with Different Morphologies Made of an Engineered Spider Silk Protein , 2012 .

[61]  D. Kaplan,et al.  Purification and characterization of recombinant spider silk expressed in Escherichia coli , 1998, Applied Microbiology and Biotechnology.

[62]  R Langer,et al.  Collagen in tissue‐engineered cartilage: Types, structure, and crosslinks , 1998, Journal of cellular biochemistry.

[63]  T. Scheibel,et al.  Recombinant spider silk-based bioinks , 2017, Biofabrication.

[64]  T. Scheibel,et al.  Engineering of recombinant spider silk proteins allows defined uptake and release of substances. , 2015, Journal of pharmaceutical sciences.

[65]  David L. Kaplan,et al.  Influence of silk-silica fusion protein design on silica condensation in vitro and cellular calcification. , 2016, RSC advances.

[66]  Michael V Sefton,et al.  Endotoxin: the uninvited guest. , 2005, Biomaterials.

[67]  M. Hedhammar,et al.  Assembly of functionalized silk together with cells to obtain proliferative 3D cultures integrated in a network of ECM-like microfibers , 2019, Scientific Reports.

[68]  Joseph Christakiran Moses,et al.  Insight into Silk-Based Biomaterials: From Physicochemical Attributes to Recent Biomedical Applications. , 2019, ACS applied bio materials.

[69]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[70]  Ung-Jin Kim,et al.  Structure and properties of silk hydrogels. , 2004, Biomacromolecules.

[71]  H. Kessler,et al.  Cell adhesion and proliferation on RGD-modified recombinant spider silk proteins. , 2012, Biomaterials.

[72]  D. Kaplan,et al.  Characterization and optimization of RGD-containing silk blends to support osteoblastic differentiation. , 2008, Biomaterials.

[73]  T. Scheibel,et al.  Controlled hydrogel formation of a recombinant spider silk protein. , 2011, Biomacromolecules.

[74]  T. Scheibel,et al.  Influence of repeat numbers on self-assembly rates of repetitive recombinant spider silk proteins. , 2014, Journal of structural biology.

[75]  T. Scheibel,et al.  Microfluidics-Produced Collagen Fibers Show Extraordinary Mechanical Properties. , 2016, Nano letters.

[76]  Thomas Scheibel,et al.  Recombinant spider silk proteins for applications in biomaterials. , 2010, Macromolecular bioscience.

[77]  P. Vogt,et al.  In Vitro Evaluation of Spider Silk Meshes as a Potential Biomaterial for Bladder Reconstruction , 2015, PloS one.

[78]  D. Porter,et al.  Proline and processing of spider silks. , 2008, Biomacromolecules.

[79]  N. Ayoub,et al.  Untangling spider silk evolution with spidroin terminal domains , 2010, BMC Evolutionary Biology.

[80]  S. Wohlrab,et al.  Controllable cell adhesion, growth and orientation on layered silk protein films. , 2013, Biomaterials science.

[81]  O. Hermanson,et al.  Recombinant spider silk protein matrices facilitate multi-analysis of calcium-signaling in neural stem cell-derived AMPA-responsive neurons , 2019, bioRxiv.

[82]  S. Rammensee,et al.  Rheological characterization of hydrogels formed by recombinantly produced spider silk , 2006 .

[83]  Thomas Scheibel,et al.  Engineering of silk proteins for materials applications. , 2019, Current opinion in biotechnology.

[84]  T. Scheibel,et al.  Interactions of cells with silk surfaces , 2012 .

[85]  T. Scheibel,et al.  Biomimetic Fibers Made of Recombinant Spidroins with the Same Toughness as Natural Spider Silk , 2015, Advanced materials.

[86]  S. Wohlrab,et al.  Structural characterization and functionalization of engineered spider silk films , 2010 .

[87]  Masaru Tomita,et al.  Orb-weaving spider Araneus ventricosus genome elucidates the spidroin gene catalogue , 2019, Scientific Reports.

[88]  T. Scheibel,et al.  Strategies and Molecular Design Criteria for 3D Printable Hydrogels. , 2016, Chemical reviews.

[89]  G. Verbruggen,et al.  Silkworm and spider silk scaffolds for chondrocyte support , 2008, Journal of materials science. Materials in medicine.

[90]  Thomas Scheibel,et al.  Hierarchical structures made of proteins. The complex architecture of spider webs and their constituent silk proteins. , 2010, Chemical Society reviews.

[91]  C. V. van Blitterswijk,et al.  Biomimetic calcium phosphate coatings on recombinant spider silk fibres , 2010, Biomedical materials.

[92]  R. Wells The role of matrix stiffness in regulating cell behavior , 2008, Hepatology.