Sulfated polysaccharide-based scaffolds for orthopaedic tissue engineering.

Given their native-like biological properties, high growth factor retention capacity and porous nature, sulfated-polysaccharide-based scaffolds hold great promise for a number of tissue engineering applications. Specifically, as they mimic important properties of tissues such as bone and cartilage they are ideal for orthopaedic tissue engineering. Their biomimicry properties encompass important cell-binding motifs, native-like mechanical properties, designated sites for bone mineralisation and strong growth factor binding and signaling capacity. Even so, scientists in the field have just recently begun to utilise them as building blocks for tissue engineering scaffolds. Most of these efforts have so far been directed towards in vitro studies, and for these reasons the clinical gap is still substantial. With this review paper, we have tried to highlight some of the important chemical, physical and biological features of sulfated-polysaccharides in relation to their chondrogenic and osteogenic inducing capacity. Additionally, their usage in various in vivo model systems is discussed. The clinical studies reviewed herein paint a promising picture heralding a brave new world for orthopaedic tissue engineering.

[1]  J D Mabrey,et al.  An interspecies comparison of bone fracture properties. , 1998, Bio-medical materials and engineering.

[2]  Huipin Yuan,et al.  Mussel-Inspired Tissue-Adhesive Hydrogel Based on the Polydopamine-Chondroitin Sulfate Complex for Growth-Factor-Free Cartilage Regeneration. , 2018, ACS applied materials & interfaces.

[3]  Xinqiao Jia,et al.  Perlecan domain I-conjugated, hyaluronic acid-based hydrogel particles for enhanced chondrogenic differentiation via BMP-2 release. , 2009, Biomaterials.

[4]  Paul Langan,et al.  Crystal structure and hydrogen-bonding system in cellulose Ibeta from synchrotron X-ray and neutron fiber diffraction. , 2002, Journal of the American Chemical Society.

[5]  Changsheng Liu,et al.  Enhanced bioactivity of bone morphogenetic protein-2 with low dose of 2-N, 6-O-sulfated chitosan in vitro and in vivo. , 2009, Biomaterials.

[6]  M. Murali,et al.  Incorporation of Fucoidan in β-Tricalcium phosphate-Chitosan scaffold prompts the differentiation of human bone marrow stromal cells into osteogenic lineage , 2016, Scientific Reports.

[7]  Syam P Nukavarapu,et al.  Osteochondral tissue engineering: current strategies and challenges. , 2013, Biotechnology advances.

[8]  F. Beier,et al.  RhoA/ROCK Signaling Suppresses Hypertrophic Chondrocyte Differentiation* , 2004, Journal of Biological Chemistry.

[9]  E. Thonar,et al.  Adult human chondrocytes cultured in alginate form a matrix similar to native human articular cartilage. , 1996, The American journal of physiology.

[10]  Jin Kim,et al.  Paper-based bioactive scaffolds for stem cell-mediated bone tissue engineering. , 2014, Biomaterials.

[11]  Duriya Fongmoon,et al.  Interaction of chondroitin sulfate and dermatan sulfate from various biological sources with heparin-binding growth factors and cytokines , 2012, Glycoconjugate Journal.

[12]  N. M. Mestechkina,et al.  Sulfated polysaccharides and their anticoagulant activity: A review , 2010, Applied Biochemistry and Microbiology.

[13]  B. Mulloy,et al.  The anticoagulant and antithrombotic mechanisms of heparin. , 2012, Handbook of experimental pharmacology.

[14]  J. Steadman,et al.  Microfracture: surgical technique and rehabilitation to treat chondral defects. , 2001, Clinical orthopaedics and related research.

[15]  Robert Langer,et al.  Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells , 2007, Proceedings of the National Academy of Sciences.

[16]  Glenn D Prestwich,et al.  Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2. , 2012, Biomaterials.

[17]  L. Cegelski,et al.  Phosphoethanolamine cellulose: A naturally produced chemically modified cellulose , 2018, Science.

[18]  Kai Zhao,et al.  Biomedical Applications of Chitosan and Its Derivative Nanoparticles , 2018, Polymers.

[19]  T. Webster,et al.  A review of fibrin and fibrin composites for bone tissue engineering , 2017, International journal of nanomedicine.

[20]  K. Takaoka,et al.  Heparin Potentiates the in Vivo Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2* , 2006, Journal of Biological Chemistry.

[21]  B. Olwin,et al.  Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation , 1991, Science.

[22]  J. Esko,et al.  Proteoglycans and Sulfated Glycosaminoglycans , 2009 .

[23]  Gulden Camci-Unal,et al.  Synthesis and characterization of hybrid hyaluronic acid-gelatin hydrogels. , 2013, Biomacromolecules.

[24]  L. Hofbauer,et al.  Sulfated Glycosaminoglycans Support Osteoblast Functions and Concurrently Suppress Osteoclasts , 2014, Journal of cellular biochemistry.

[25]  D. Scharnweber,et al.  Interactions of collagen types I and II with chondroitin sulfates A-C and their effect on osteoblast adhesion. , 2007, Biomacromolecules.

[26]  A. Mikos,et al.  Effect of swelling ratio of injectable hydrogel composites on chondrogenic differentiation of encapsulated rabbit marrow mesenchymal stem cells in vitro. , 2009, Biomacromolecules.

[27]  Wei Zhang,et al.  Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair. , 2017, Acta biomaterialia.

[28]  C. Scopa,et al.  Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits. , 2009, Medical science monitor : international medical journal of experimental and clinical research.

[29]  K. Swaminathan,et al.  A Heparan Sulfate Device for the Regeneration of Osteochondral Defects. , 2019, Tissue engineering. Part A.

[30]  M. Murali,et al.  Three dimensional alginate-fucoidan composite hydrogel augments the chondrogenic differentiation of mesenchymal stromal cells. , 2016, Carbohydrate polymers.

[31]  D. Kelly,et al.  Hydrostatic pressure acts to stabilise a chondrogenic phenotype in porcine joint tissue derived stem cells. , 2012, European cells & materials.

[32]  Frank Witte,et al.  Simultaneous regeneration of articular cartilage and subchondral bone induced by spatially presented TGF-beta and BMP-4 in a bilayer affinity binding system. , 2012, Acta biomaterialia.

[33]  G. Embery,et al.  Interaction of glucuronic acid and iduronic acid-rich glycosaminoglycans and their modified forms with hydroxyapatite. , 2002, Biomaterials.

[34]  Amit Bandyopadhyay,et al.  Recent advances in bone tissue engineering scaffolds. , 2012, Trends in biotechnology.

[35]  Shyni Varghese,et al.  Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. , 2008, Matrix biology : journal of the International Society for Matrix Biology.

[36]  Teerasak Damrongrungruang,et al.  Silk fibroin/gelatin-chondroitin sulfate-hyaluronic acid effectively enhances in vitro chondrogenesis of bone marrow mesenchymal stem cells. , 2015, Materials science & engineering. C, Materials for biological applications.

[37]  A. Atala,et al.  Carbon nanotube applications for tissue engineering. , 2007, Biomaterials.

[38]  R. Schweiger Polysaccharide sulfates. I. cellulose sulfate with a high degree of substitution , 1972 .

[39]  Mingzhu Liu,et al.  An injectable and self-healing hydrogel with covalent cross-linking in vivo for cranial bone repair. , 2017, Journal of materials chemistry. B.

[40]  B. Xia,et al.  Enhancing effects of basic fibroblast growth factor and fibronectin on osteoblast adhesion to bone scaffolds for bone tissue engineering through extracellular matrix-integrin pathway. , 2017, Experimental and therapeutic medicine.

[41]  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.

[42]  Aurelien Forget,et al.  Discovering Cell-Adhesion Peptides in Tissue Engineering: Beyond RGD. , 2018, Trends in biotechnology.

[43]  D. Mooney,et al.  Growth factor delivery-based tissue engineering: general approaches and a review of recent developments , 2011, Journal of The Royal Society Interface.

[44]  J. Mao,et al.  A preliminary study on chitosan and gelatin polyelectrolyte complex cytocompatibility by cell cycle and apoptosis analysis. , 2004, Biomaterials.

[45]  Jennifer S. Park,et al.  The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. , 2011, Biomaterials.

[46]  K. Yeung,et al.  Bone grafts and biomaterials substitutes for bone defect repair: A review , 2017, Bioactive materials.

[47]  C. Stevens,et al.  Recent developments in antibacterial and antifungal chitosan and its derivatives. , 2017, Carbohydrate polymers.

[48]  A. Hanssen,et al.  Limitations of Structural Allograft in Revision Total Knee Arthroplasty , 2009, Clinical orthopaedics and related research.

[49]  S. Bryant,et al.  Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering. , 2015, Acta biomaterialia.

[50]  T. Rachner,et al.  The effect of the degree of sulfation of glycosaminoglycans on osteoclast function and signaling pathways. , 2012, Biomaterials.

[51]  R. Reis,et al.  Encapsulation of adipose-derived stem cells and transforming growth factor-β1 in carrageenan-based hydrogels for cartilage tissue engineering , 2011 .

[52]  C. Semino,et al.  Chondroitin Sulfate- and Decorin-Based Self-Assembling Scaffolds for Cartilage Tissue Engineering , 2016, PloS one.

[53]  H. Tønnesen,et al.  Alginate in Drug Delivery Systems , 2002, Drug development and industrial pharmacy.

[54]  Smadar Cohen,et al.  The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins. , 2008, Biomaterials.

[55]  E. Place,et al.  Complexity in biomaterials for tissue engineering. , 2009, Nature materials.

[56]  B. Größner-Schreiber,et al.  Influence of collagen and chondroitin sulfate (CS) coatings on poly-(lactide-co-glycolide) (PLGA) on MG 63 osteoblast-like cells. , 2011, Physiological research.

[57]  Changsheng Liu,et al.  Enhanced osteogenesis of bone morphology protein-2 in 2-N,6-O-sulfated chitosan immobilized PLGA scaffolds. , 2014, Colloids and surfaces. B, Biointerfaces.

[58]  J. Kanis,et al.  Burden of high fracture probability worldwide: secular increases 2010–2040 , 2015, Osteoporosis International.

[59]  Gordon G Wallace,et al.  Three-Dimensional Printing and Cell Therapy for Wound Repair. , 2018, Advances in wound care.

[60]  Liming Bian,et al.  Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy. , 2017, Acta biomaterialia.

[61]  H. Maynard,et al.  Heparin-Mimicking Polymers: Synthesis and Biological Applications , 2016, Biomacromolecules.

[62]  Changsheng Liu,et al.  Biomimetic porous scaffolds for bone tissue engineering , 2014 .

[63]  J. W. E. Brading,et al.  The polysaccharide from the alga Ulva lactuca. Purification, hydrolysis, and methylation of the polysaccharide , 1954 .

[64]  Jos Malda,et al.  A Synthetic Thermosensitive Hydrogel for Cartilage Bioprinting and Its Biofunctionalization with Polysaccharides. , 2016, Biomacromolecules.

[65]  Min Zhang,et al.  Toward delivery of multiple growth factors in tissue engineering. , 2010, Biomaterials.

[66]  U. Pietsch,et al.  κ-Carrageenan Enhances the Biomineralization and Osteogenic Differentiation of Electrospun Polyhydroxybutyrate and Polyhydroxybutyrate Valerate Fibers. , 2017, Biomacromolecules.

[67]  R. Soares,et al.  Immobilization of human mesenchymal stem cells within RGD-grafted alginate microspheres and assessment of their angiogenic potential. , 2010, Biomacromolecules.

[68]  P. Dubruel,et al.  Biofunctionalization of ulvan scaffolds for bone tissue engineering. , 2014, ACS applied materials & interfaces.

[69]  N. Abu-Ghannam,et al.  Bioactive potential and possible health effects of edible brown seaweeds , 2011 .

[70]  Ralph Müller,et al.  Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing , 2011, Science Translational Medicine.

[71]  Wojciech Święszkowski,et al.  3D bioprinting of BM-MSCs-loaded ECM biomimetic hydrogels for in vitro neocartilage formation , 2016, Biofabrication.

[72]  Qian Feng,et al.  Effect of cartilaginous matrix components on the chondrogenesis and hypertrophy of mesenchymal stem cells in hyaluronic acid hydrogels. , 2017, Journal of biomedical materials research. Part B, Applied biomaterials.

[73]  Lauren M. Cross,et al.  Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces. , 2016, Acta biomaterialia.

[74]  Mehdi Nikkhah,et al.  Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load‐Bearing and Electroactive Tissues , 2017, Advanced materials.

[75]  T. Vos,et al.  Global, regional, and national incidence and prevalence, and years lived with disability for 328 diseases and injuries in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 , 2017 .

[76]  E. Yates,et al.  New Applications of Heparin and Other Glycosaminoglycans , 2017, Molecules.

[77]  N. Iwasaki,et al.  Sulfation patterns of exogenous chondroitin sulfate affect chondrogenic differentiation of ATDC5 cells , 2014, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[78]  L. Bonassar,et al.  Chondrocyte calcium signaling in response to fluid flow is regulated by matrix adhesion in 3-D alginate scaffolds. , 2011, Archives of biochemistry and biophysics.

[79]  A. Yee,et al.  Structure and function of aggrecan , 2002, Cell Research.

[80]  P. Klokkevold,et al.  Osteogenesis enhanced by chitosan (poly-N-acetyl glucosaminoglycan) in vitro. , 1996, Journal of periodontology.

[81]  Xinqiao Jia,et al.  Heparin-decorated, hyaluronic acid-based hydrogel particles for the controlled release of bone morphogenetic protein 2. , 2011, Acta biomaterialia.

[82]  J. Elisseeff,et al.  Advances in skeletal tissue engineering with hydrogels. , 2005, Orthodontics & craniofacial research.

[83]  Claudio Migliaresi,et al.  Heparin functionalization increases retention of TGF-β2 and GDF5 on biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering. , 2018, Acta biomaterialia.

[84]  T. Arinzeh,et al.  Investigating cellulose derived glycosaminoglycan mimetic scaffolds for cartilage tissue engineering applications , 2018, Journal of tissue engineering and regenerative medicine.

[85]  Ha Na Kim,et al.  Chitosan‐Based Heparan Sulfate Mimetics Promote Epidermal Formation in a Human Organotypic Skin Model , 2018, Advanced Functional Materials.

[86]  R. Burgkart,et al.  Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model , 2016, PloS one.

[87]  Karim Senni,et al.  Marine Polysaccharides: A Source of Bioactive Molecules for Cell Therapy and Tissue Engineering , 2011, Marine drugs.

[88]  Alvaro Mata,et al.  Bimolecular based heparin and self-assembling hydrogel for tissue engineering applications. , 2015, Acta biomaterialia.

[89]  G. Schulze-Tanzil,et al.  Chondrogenesis of human bone marrow mesenchymal stromal cells in highly porous alginate-foams supplemented with chondroitin sulfate. , 2015, Materials science & engineering. C, Materials for biological applications.

[90]  D. Kelly,et al.  Tuning Alginate Bioink Stiffness and Composition for Controlled Growth Factor Delivery and to Spatially Direct MSC Fate within Bioprinted Tissues , 2017, Scientific Reports.

[91]  Heungsoo Shin,et al.  Biomimetic Scaffolds for Tissue Engineering , 2012 .

[92]  Dietmar W. Hutmacher,et al.  A biomimetic extracellular matrix for cartilage tissue engineering centered on photocurable gelatin, hyaluronic acid and chondroitin sulfate. , 2014, Acta biomaterialia.

[93]  Bo Li,et al.  Fucoidan: Structure and Bioactivity , 2008, Molecules.

[94]  Barry J Doyle,et al.  Mechanical behaviour of alginate-gelatin hydrogels for 3D bioprinting. , 2018, Journal of the mechanical behavior of biomedical materials.

[95]  Changsheng Liu,et al.  Enhancement of BMP-2-mediated angiogenesis and osteogenesis by 2-N,6-O-sulfated chitosan in bone regeneration. , 2017, Biomaterials science.

[96]  P. Dubin,et al.  Electrostatic Forces as Dominant Interactions Between Proteins and Polyanions: an ESI MS Study of Fibroblast Growth Factor Binding to Heparin Oligomers , 2017, Journal of The American Society for Mass Spectrometry.

[97]  R. Vasita,et al.  Improved biomaterials for tissue engineering applications: surface modification of polymers. , 2008, Current topics in medicinal chemistry.

[98]  L. Hofbauer,et al.  Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function. , 2016, Biomaterials.

[99]  R. Reis,et al.  Chondrogenic phenotype of different cells encapsulated in κ‐carrageenan hydrogels for cartilage regeneration strategies , 2012, Biotechnology and applied biochemistry.

[100]  M. Lyon,et al.  The Interaction of the Transforming Growth Factor-βs with Heparin/Heparan Sulfate Is Isoform-specific* , 1997, The Journal of Biological Chemistry.

[101]  Eveliina Lammentausta,et al.  Cellulose sponge as a scaffold for cartilage tissue engineering. , 2006, Bio-medical materials and engineering.

[102]  Nathaniel S. Hwang,et al.  Chondroitin Sulfate-Based Biomineralizing Surface Hydrogels for Bone Tissue Engineering. , 2017, ACS applied materials & interfaces.

[103]  T. Arinzeh,et al.  * Gelatin Scaffolds Containing Partially Sulfated Cellulose Promote Mesenchymal Stem Cell Chondrogenesis. , 2017, Tissue engineering. Part A.

[104]  Caixia Xu,et al.  Exogenous Heparan Sulfate Enhances the TGF-β3-Induced Chondrogenesis in Human Mesenchymal Stem Cells by Activating TGF-β/Smad Signaling , 2015, Stem cells international.

[105]  Ryan J. Weiss,et al.  Targeting heparin and heparan sulfate protein interactions. , 2017, Organic & biomolecular chemistry.

[106]  R. Reis,et al.  Fabrication of endothelial cell-laden carrageenan microfibers for microvascularized bone tissue engineering applications. , 2014, Biomacromolecules.

[107]  Gaurav Baranwal,et al.  Composite hydrogel of chitosan-poly(hydroxybutyrate-co-valerate) with chondroitin sulfate nanoparticles for nucleus pulposus tissue engineering. , 2015, Colloids and surfaces. B, Biointerfaces.

[108]  Xinqiao Jia,et al.  Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis , 2012, Biomedical materials.

[109]  Lina Zhang,et al.  Rubbery Chitosan/Carrageenan Hydrogels Constructed through an Electroneutrality System and Their Potential Application as Cartilage Scaffolds. , 2018, Biomacromolecules.

[110]  Fengjuan Chen,et al.  Biomimetic and cell-mediated mineralization of hydroxyapatite by carrageenan functionalized graphene oxide. , 2014, ACS applied materials & interfaces.

[111]  S. Stock,et al.  Bone regeneration with low dose BMP-2 amplified by biomimetic supramolecular nanofibers within collagen scaffolds. , 2013, Biomaterials.

[112]  Ying Mei,et al.  Engineering alginate as bioink for bioprinting. , 2014, Acta biomaterialia.

[113]  David J. Mooney,et al.  Growth Factors, Matrices, and Forces Combine and Control Stem Cells , 2009, Science.

[114]  Todd C McDevitt,et al.  Heparin microparticle effects on presentation and bioactivity of bone morphogenetic protein-2. , 2014, Biomaterials.

[115]  S. Roberts,et al.  Immunohistochemical study of collagen types I and II and procollagen IIA in human cartilage repair tissue following autologous chondrocyte implantation , 2009, The Knee.

[116]  Rui L. Reis,et al.  Chondrogenic potential of injectable κ‐carrageenan hydrogel with encapsulated adipose stem cells for cartilage tissue‐engineering applications , 2015, Journal of tissue engineering and regenerative medicine.

[117]  N Selvamurugan,et al.  A review of chitosan and its derivatives in bone tissue engineering. , 2016, Carbohydrate polymers.

[118]  D. Mooney,et al.  Alginate: properties and biomedical applications. , 2012, Progress in polymer science.

[119]  Jason A. Burdick,et al.  Hyaluronic Acid Hydrogels for Biomedical Applications , 2011, Advanced materials.

[120]  Changyong Wang,et al.  Iota-carrageenan/chitosan/gelatin scaffold for the osteogenic differentiation of adipose-derived MSCs in vitro. , 2015, Journal of biomedical materials research. Part B, Applied biomaterials.

[121]  M. Pardue,et al.  The Journal of Cell Biology , 2002 .

[122]  J. Abrahams,et al.  The anticoagulant activation of antithrombin by heparin. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[123]  E. Wood,et al.  Fucoidan modulates the effect of transforming growth factor (TGF)-beta1 on fibroblast proliferation and wound repopulation in in vitro models of dermal wound repair. , 2004, Biological & pharmaceutical bulletin.

[124]  ZhiYong Qian,et al.  Biodegradable CSMA/PECA/Graphene Porous Hybrid Scaffold for Cartilage Tissue Engineering , 2015, Scientific Reports.

[125]  Antonios G Mikos,et al.  Tissue Engineering in Orthopaedics. , 2016, The Journal of bone and joint surgery. American volume.

[126]  S. Waldman,et al.  Chondrocyte Generation of Cartilage-Like Tissue Following Photoencapsulation in Methacrylated Polysaccharide Solution Blends. , 2016, Macromolecular bioscience.

[127]  R. Reis,et al.  Marine algae sulfated polysaccharides for tissue engineering and drug delivery approaches , 2012, Biomatter.

[128]  Chia-Chen Hsu,et al.  Arthroscopic cartilage regeneration facilitating procedure for osteoarthritic knee , 2012, BMC Musculoskeletal Disorders.

[129]  J. Bonaventure,et al.  Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads. , 1994, Experimental cell research.

[130]  G. Davis,et al.  Identification of Dual α4β1 Integrin Binding Sites within a 38 Amino Acid Domain in the N-terminal Thrombin Fragment of Human Osteopontin* , 2001, The Journal of Biological Chemistry.

[131]  Marco Rusnati,et al.  Heparin/Heparan Sulfate Proteoglycans Glycomic Interactome in Angiogenesis: Biological Implications and Therapeutical Use , 2015, Molecules.

[132]  M. Zenobi‐Wong,et al.  Chondrocyte culture in three dimensional alginate sulfate hydrogels promotes proliferation while maintaining expression of chondrogenic markers. , 2014, Tissue engineering. Part A.

[133]  Rui R. Costa,et al.  Chitosan/Chondroitin Sulfate Membranes Produced by Polyelectrolyte Complexation for Cartilage Engineering. , 2016, Biomacromolecules.

[134]  Gordon G Wallace,et al.  Biopolymers for Antitumor Implantable Drug Delivery Systems: Recent Advances and Future Outlook , 2018, Advanced materials.

[135]  J. Werkmeister,et al.  Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles. , 2014, Biomaterials.

[136]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[137]  P. Fratzl,et al.  Increased bone remodelling around titanium implants coated with chondroitin sulfate in ovariectomized rats. , 2014, Acta biomaterialia.

[138]  D. Rabenstein Heparin and heparan sulfate: structure and function. , 2002, Natural product reports.

[139]  Ricardo Bentini,et al.  The performance of bone tissue engineering scaffolds in in vivo animal models: A systematic review , 2016, Journal of biomaterials applications.

[140]  H. Kitagawa,et al.  Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate. , 2003, Current opinion in structural biology.

[141]  Rui L Reis,et al.  Natural‐Based Nanocomposites for Bone Tissue Engineering and Regenerative Medicine: A Review , 2015, Advanced materials.

[142]  Rui Luís Reis,et al.  Seaweed polysaccharide-based hydrogels used for the regeneration of articular cartilage , 2015, Critical reviews in biotechnology.

[143]  K. Athanasiou,et al.  Extracellular matrix cell adhesion peptides: functional applications in orthopedic materials. , 2000, Tissue engineering.

[144]  D. Scharnweber,et al.  Sulfated hyaluronan/collagen I matrices enhance the osteogenic differentiation of human mesenchymal stromal cells in vitro even in the absence of dexamethasone. , 2012, Acta biomaterialia.

[145]  M. Anselmi,et al.  Sulfated glycosaminoglycans exploit the conformational plasticity of bone morphogenetic protein-2 (BMP-2) and alter the interaction profile with its receptor. , 2014, Biomacromolecules.

[146]  David J Mooney,et al.  Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix. , 2007, Biomaterials.

[147]  J. Melrose,et al.  Harnessing chondroitin sulphate in composite scaffolds to direct progenitor and stem cell function for tissue repair. , 2018, Biomaterials science.

[148]  Paniz Motaghi,et al.  Long-term Results, Functional Outcomes and Complications after Open Reduction and Internal Fixation of Neglected and Displaced Greater Tuberosity of Humerus Fractures. , 2016, The archives of bone and joint surgery.

[149]  Paul A. Rundquist,et al.  Advances in cellulose ester performance and application , 2001 .

[150]  François Berthiaume,et al.  Tissue Engineering and Regenerative Medicine : History , Progress , and Challenges , 2013 .

[151]  A. Subramanian,et al.  Injectable and 3D Bioprinted Polysaccharide Hydrogels: From Cartilage to Osteochondral Tissue Engineering. , 2017, Biomacromolecules.

[152]  P. Manivasagan,et al.  Marine polysaccharide-based nanomaterials as a novel source of nanobiotechnological applications. , 2016, International journal of biological macromolecules.

[153]  Mark Van Dyke,et al.  Biomimetic approaches to modulate cellular adhesion in biomaterials: A review. , 2013, Acta biomaterialia.

[154]  Kieran P Fuller,et al.  Harnessing Hierarchical Nano‐ and Micro‐Fabrication Technologies for Musculoskeletal Tissue Engineering , 2015, Advanced healthcare materials.

[155]  Robert A. Anderson,et al.  Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent. , 2002, Journal of andrology.

[156]  A. Gaharwar,et al.  Pectin Methacrylate (PEMA) and Gelatin-Based Hydrogels for Cell Delivery: Converting Waste Materials into Biomaterials. , 2019, ACS applied materials & interfaces.

[157]  Pawan Kumar Gupta,et al.  Glycosaminoglycans enhance osteoblast differentiation of bone marrow derived human mesenchymal stem cells , 2014, Journal of tissue engineering and regenerative medicine.

[158]  Changsheng Liu,et al.  Vascularization and bone regeneration in a critical sized defect using 2-N,6-O-sulfated chitosan nanoparticles incorporating BMP-2. , 2014, Biomaterials.

[159]  G. Stein,et al.  Bone marrow-derived heparan sulfate potentiates the osteogenic activity of bone morphogenetic protein-2 (BMP-2). , 2012, Bone.

[160]  K. Tang,et al.  A novel composite of collagen-hydroxyapatite/kappa-carrageenan , 2017 .

[161]  Ø. Arlov,et al.  Sulfated Alginates as Heparin Analogues: A Review of Chemical and Functional Properties , 2017, Molecules.

[162]  R. Kamijo,et al.  Sulfated Polysaccharides Enhance the Biological Activities of Bone Morphogenetic Proteins* , 2003, Journal of Biological Chemistry.

[163]  Xing‐dong Zhang,et al.  Therapy for cartilage defects: functional ectopic cartilage constructed by cartilage-simulating collagen, chondroitin sulfate and hyaluronic acid (CCH) hybrid hydrogel with allogeneic chondrocytes. , 2018, Biomaterials science.

[164]  J. Temenoff,et al.  The effect of desulfation of chondroitin sulfate on interactions with positively charged growth factors and upregulation of cartilaginous markers in encapsulated MSCs. , 2013, Biomaterials.

[165]  M. Mehrali,et al.  Fabrication and in vitro biological activity of βTCP-Chitosan-Fucoidan composite for bone tissue engineering. , 2015, Carbohydrate polymers.

[166]  Byung-Soo Kim,et al.  Heparin-conjugated fibrin as an injectable system for sustained delivery of bone morphogenetic protein-2. , 2010, Tissue engineering. Part A.

[167]  Łukasz Mencner,et al.  Diverse Roles of Heparan Sulfate and Heparin in Wound Repair , 2015, BioMed research international.

[168]  J. H. Lee,et al.  Repair of osteochondral defects with adipose stem cells and a dual growth factor-releasing scaffold in rabbits. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[169]  Jae Young Lee,et al.  Three dimensional cell printing with sulfated alginate for improved bone morphogenetic protein-2 delivery and osteogenesis in bone tissue engineering. , 2018, Carbohydrate polymers.

[170]  W. Bugbee,et al.  Fresh osteochondral allograft transplantation for the knee: current concepts. , 2014, The Journal of the American Academy of Orthopaedic Surgeons.

[171]  S. Selleck,et al.  Order out of chaos: assembly of ligand binding sites in heparan sulfate. , 2002, Annual review of biochemistry.

[172]  Stefan Rammelt,et al.  Coating of titanium implants with collagen, RGD peptide and chondroitin sulfate. , 2006, Biomaterials.

[173]  P. Benya,et al.  Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels , 1982, Cell.

[174]  Sara M. Oliveira,et al.  Nanocoatings containing sulfated polysaccharides prepared by layer-by-layer assembly as models to study cell-material interactions. , 2013, Journal of materials chemistry. B.

[175]  You-Jin Jeon,et al.  Biological activities and potential industrial applications of fucose rich sulfated polysaccharides and fucoidans isolated from brown seaweeds: A review , 2012 .

[176]  Alireza Dolatshahi-Pirouz,et al.  Interaction of human mesenchymal stem cells with osteopontin coated hydroxyapatite surfaces. , 2010, Colloids and surfaces. B, Biointerfaces.

[177]  Guangli Yu,et al.  Chemical Structures and Bioactivities of Sulfated Polysaccharides from Marine Algae , 2011, Marine drugs.

[178]  Akhilesh K. Gaharwar,et al.  Injectable shear-thinning nanoengineered hydrogels for stem cell delivery. , 2016, Nanoscale.

[179]  D. Scharnweber,et al.  Sulfated hyaluronan and chondroitin sulfate derivatives interact differently with human transforming growth factor-β1 (TGF-β1). , 2012, Acta biomaterialia.

[180]  Sung‐Wook Choi,et al.  Fabrication of a BMP-2-immobilized porous microsphere modified by heparin for bone tissue engineering. , 2015, Colloids and surfaces. B, Biointerfaces.

[181]  J. Melrose,et al.  Can We Produce Heparin/Heparan Sulfate Biomimetics Using “Mother-Nature” as the Gold Standard? , 2015, Molecules.

[182]  B. Farrugia,et al.  Synthesis and characterization of water soluble biomimetic chitosans for bone and cartilage tissue regeneration. , 2014, Journal of materials chemistry. B.

[183]  H. S. Azevedo,et al.  Novel injectable gel (system) as a vehicle for human articular chondrocytes in cartilage tissue regeneration , 2009, Journal of tissue engineering and regenerative medicine.

[184]  J. Boateng,et al.  Wound healing dressings and drug delivery systems: a review. , 2008, Journal of pharmaceutical sciences.

[185]  T. Kyriakides,et al.  Nanomaterials, inflammation, and tissue engineering. , 2015, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[186]  M. Foss,et al.  Osteopontin functionalization of hydroxyapatite nanoparticles in a PDLLA matrix promotes bone formation. , 2011, Journal of biomedical materials research. Part A.

[187]  Rui L Reis,et al.  Assembling Human Platelet Lysate into Multiscale 3D Scaffolds for Bone Tissue Engineering. , 2015, ACS biomaterials science & engineering.

[188]  J. Couchman,et al.  Syndecans as receptors and organizers of the extracellular matrix , 2009, Cell and Tissue Research.

[189]  K. Urayama,et al.  Preparation and Electrochemical Properties of Alginate Sulfate Electrolyte Membranes , 2008 .

[190]  E. Ruoslahti,et al.  A novel integrin specificity exemplified by binding of the alpha v beta 5 integrin to the basic domain of the HIV Tat protein and vitronectin , 1993, The Journal of cell biology.

[191]  Yongfeng Zhou,et al.  An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering , 2016, Scientific Reports.

[192]  T. Spector,et al.  Osteoarthritis: New Insights. Part 1: The Disease and Its Risk Factors , 2000, Annals of Internal Medicine.

[193]  In-Yong Kim,et al.  Chitosan and its derivatives for tissue engineering applications. , 2008, Biotechnology advances.

[194]  Filippo Causa,et al.  Bioactive scaffolds for bone and ligament tissue , 2007, Expert review of medical devices.

[195]  S. Bellis,et al.  Advantages of RGD peptides for directing cell association with biomaterials. , 2011, Biomaterials.