Enhanced dual network hydrogels consisting of thiolated chitosan and silk fibroin for cartilage tissue engineering.

Thiolated chitosan (CS-NAC) was synthesized and the selected CS-NAC was used together with silk fibroin (SF) to produce dual network CS-NAC/SF hydrogels. The CS-NAC/SF solutions with formulated compositions were able to form hydrogels at physiological temperature and pH. Rheological measurements showed that elastic modulus of some CS-NAC/SF gels could reach around 3 kPa or higher and was much higher than their respective viscous modulus, indicating that they behaved like strong gels. Deformation measurements verified that CS-NAC/SF gels had well-defined elasticity. The optimized CS-NAC/SF gels exhibited jointly enhanced properties in terms of strength, stiffness and elasticity when compared to the gels resulted from either CS-NAC or SF. Examinations of dry CS-NAC/SF gels revealed that they were highly porous with well-interconnected pore features. Cell culture demonstrated that CS-NAC/SF gels supported the growth of chondrocytes while effectively maintaining their phenotype. Results suggest that these dual network gels have promising potential in cartilage repair.

[1]  K. Oksman,et al.  Nanocellulose-Based Interpenetrating Polymer Network (IPN) Hydrogels for Cartilage Applications. , 2016, Biomacromolecules.

[2]  S. Kundu,et al.  Silk fibroin protein and chitosan polyelectrolyte complex porous scaffolds for tissue engineering applications , 2011 .

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

[4]  A. U. Daniels,et al.  Effects of scaffold composition and architecture on human nasal chondrocyte redifferentiation and cartilaginous matrix deposition. , 2005, Biomaterials.

[5]  Peter Müller,et al.  Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture , 1977, Nature.

[6]  K. Hörmann,et al.  In vitro analysis of matrix proteins and growth factors in dedifferentiating human chondrocytes for tissue-engineered cartilage , 2005, Acta oto-laryngologica.

[7]  Jerry C. Hu,et al.  The role of tissue engineering in articular cartilage repair and regeneration. , 2009, Critical reviews in biomedical engineering.

[8]  Shaoheng Tang,et al.  Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery , 2012, Molecular vision.

[9]  Kaiqiang Liu,et al.  Novel dimeric cholesteryl derivatives and their smart thixotropic gels. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[10]  Ching-Chuan Jiang,et al.  Repair of articular cartilage defects: review and perspectives. , 2009, Journal of the Formosan Medical Association = Taiwan yi zhi.

[11]  Jelena Rnjak-Kovacina,et al.  Highly Tunable Elastomeric Silk Biomaterials , 2014, Advanced functional materials.

[12]  Zohreh Izadifar,et al.  Analyzing Biological Performance of 3D-Printed, Cell-Impregnated Hybrid Constructs for Cartilage Tissue Engineering. , 2016, Tissue engineering. Part C, Methods.

[13]  J. F. Woessner,et al.  The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. , 1961, Archives of biochemistry and biophysics.

[14]  Miqin Zhang,et al.  Chitosan-based hydrogels for controlled, localized drug delivery. , 2010, Advanced drug delivery reviews.

[15]  Liu Yang,et al.  Enzymatically crosslinked and mechanically tunable silk fibroin/pullulan hydrogels for mesenchymal stem cells delivery. , 2018, International journal of biological macromolecules.

[16]  Jiyoung M Dang,et al.  Temperature-responsive hydroxybutyl chitosan for the culture of mesenchymal stem cells and intervertebral disk cells. , 2006, Biomaterials.

[17]  Federica Chiellini,et al.  Chitosan—A versatile semi-synthetic polymer in biomedical applications , 2011 .

[18]  Farshid Guilak,et al.  The biomechanical role of the chondrocyte pericellular matrix in articular cartilage. , 2005, Acta biomaterialia.

[19]  R. Muzzarelli Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone , 2009 .

[20]  Helen H. Lu,et al.  Engineering Complex Orthopaedic Tissues Via Strategic Biomimicry , 2015, Annals of Biomedical Engineering.

[21]  X. Wang,et al.  Chitosan-NAC nanoparticles as a vehicle for nasal absorption enhancement of insulin. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[22]  D. Kaplan,et al.  The consolidation behavior of silk hydrogels. , 2010, Journal of the mechanical behavior of biomedical materials.

[23]  F. Luyten,et al.  Cartilage repair: past and future – lessons for regenerative medicine , 2009, Journal of cellular and molecular medicine.

[24]  V Vécsei,et al.  Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. , 2002, Osteoarthritis and cartilage.

[25]  E B Hunziker,et al.  Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. , 2002, Osteoarthritis and cartilage.

[26]  I. Martin,et al.  The regulation of expanded human nasal chondrocyte re-differentiation capacity by substrate composition and gas plasma surface modification. , 2006, Biomaterials.

[27]  Antonios G Mikos,et al.  Injectable matrices and scaffolds for drug delivery in tissue engineering. , 2007, Advanced drug delivery reviews.

[28]  Q. Cai,et al.  In vitro BMP-2 peptide release from thiolated chitosan based hydrogel. , 2016, International journal of biological macromolecules.

[29]  J A Burdick,et al.  Recent advances in hydrogels for cartilage tissue engineering. , 2017, European cells & materials.

[30]  Tae Gwan Park,et al.  Catechol-functionalized chitosan/pluronic hydrogels for tissue adhesives and hemostatic materials. , 2011, Biomacromolecules.

[31]  Shantikumar V. Nair,et al.  An overview of injectable polymeric hydrogels for tissue engineering , 2015 .

[32]  D. W. Jackson,et al.  Cartilage Substitutes: Overview of Basic Science and Treatment Options , 2001, The Journal of the American Academy of Orthopaedic Surgeons.

[33]  M. Detamore,et al.  Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application. , 2009, Osteoarthritis and cartilage.

[34]  Pei Cao,et al.  Glycerophosphate-based chitosan thermosensitive hydrogels and their biomedical applications. , 2015, Carbohydrate polymers.

[35]  K. Chennazhi,et al.  Development of mucoadhesive thiolated chitosan nanoparticles for biomedical applications , 2011 .

[36]  Z. Shao,et al.  Enhancing the Gelation and Bioactivity of Injectable Silk Fibroin Hydrogel with Laponite Nanoplatelets. , 2016, ACS applied materials & interfaces.

[37]  A. Grodzinsky,et al.  Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[38]  Denis Rodrigue,et al.  Viscoelastic properties of dispersed chitosan/xanthan hydrogels , 2007 .

[39]  B. Pei,et al.  Construction of ordered structure in polysaccharide hydrogel: A review. , 2019, Carbohydrate polymers.

[40]  Xiaoying Cao,et al.  Proliferation of chondrocytes on porous poly(DL-lactide)/chitosan scaffolds. , 2008, Acta biomaterialia.

[41]  R. Müller,et al.  Effect of matrix elasticity on the maintenance of the chondrogenic phenotype. , 2010, Tissue engineering. Part A.

[42]  Christoph Weder,et al.  Articular cartilage: from formation to tissue engineering. , 2016, Biomaterials science.

[43]  Yon Jin Chuah,et al.  Hydrogel based cartilaginous tissue regeneration: recent insights and technologies. , 2017, Biomaterials science.

[44]  R. Luginbuehl,et al.  Chondrocytes expressing intracellular collagen type II enter the cell cycle and co‐express collagen type I in monolayer culture , 2014, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[45]  A. Imhoff,et al.  Operative Therapiemöglichkeiten des Knorpelschadens , 2001, Der Unfallchirurg.

[46]  Sei Kwang Hahn,et al.  In situ-forming injectable hydrogels for regenerative medicine , 2014 .

[47]  David L. Kaplan,et al.  Silk Hydrogels as Soft Substrates for Neural Tissue Engineering , 2013 .

[48]  Travis M. Shaffer,et al.  Radiation-Responsive Esculin-Derived Molecular Gels as Signal Enhancers for Optical Imaging. , 2017, ACS applied materials & interfaces.

[49]  Huaping Tan,et al.  Injectable, Biodegradable Hydrogels for Tissue Engineering Applications , 2010, Materials.

[50]  Xiguang Chen,et al.  Investigation of gelling behavior of thiolated chitosan in alkaline condition and its application in stent coating. , 2016, Carbohydrate polymers.

[51]  B. Peppley,et al.  Structure and ionic conductivity of a series of di-o-butyrylchitosan membranes , 2004 .

[52]  T. Okano,et al.  Positive thermosensitive pulsatile drug release using negative thermosensitive hydrogels , 1994 .

[53]  A. Clark,et al.  Structural and mechanical properties of biopolymer gels , 1987 .