A Tissue Regeneration Approach to Bone and Cartilage Repair

1 - Contents [Seite 6]
2 - Ligand-Receptor Interactions and Their Implications in Delivering Certain Signaling for Bone Regeneration [Seite 8]
2.1 - Abstract [Seite 8]
2.2 - 1 Introduction [Seite 8]
2.3 - 2 The Identification of BMPs as Members of the TGF-? Family [Seite 9]
2.4 - 3 Experimental Models for Evaluating Bone Formation [Seite 10]
2.5 - 4 Regulation of Ligand Modifications [Seite 11]
2.6 - 5 Regulation of Receptor Activation [Seite 12]
2.7 - 6 Regulation by Antagonists [Seite 13]
2.8 - 7 Regulation of Intracellular Signaling Effectors [Seite 15]
2.9 - 8 Cross-Talk with Other Signaling Molecules [Seite 17]
2.10 - 9 Conclusions [Seite 19]
2.11 - References [Seite 19]
3 - BMPs and Wnts in Bone and Cartilage Regeneration [Seite 23]
3.1 - Abstract [Seite 23]
3.2 - 1 BMP Signaling in Bone and Cartilage Regeneration [Seite 23]
3.2.1 - 1.1 Bmp-2 [Seite 24]
3.2.2 - 1.2 Bmp-4 [Seite 26]
3.2.2.1 - 1.2.1 Cartilage Repair [Seite 26]
3.2.2.2 - 1.2.2 Bone-Tendon-Muscle Interaction [Seite 26]
3.2.3 - 1.3 Bmp-6 [Seite 27]
3.2.3.1 - 1.3.1 Cartilage Repair [Seite 27]
3.2.3.2 - 1.3.2 Bone Regeneration [Seite 28]
3.2.4 - 1.4 Bmp-7 [Seite 28]
3.2.4.1 - 1.4.1 Cartilage Repair and Arthritis [Seite 28]
3.2.4.2 - 1.4.2 Meniscus Repair [Seite 29]
3.2.4.3 - 1.4.3 Fracture and Spinal Fusion [Seite 29]
3.2.5 - 1.5 Bmp-9 [Seite 30]
3.2.6 - 1.6 Cross-Talk Between BMP and Wnt Signaling [Seite 30]
3.3 - 2 Wnt?-Catenin Signaling in Bone and Cartilage Regeneration [Seite 31]
3.3.1 - 2.1 Scl-Ab [Seite 32]
3.3.1.1 - 2.1.1 Scl-Ab in Ovariectomy-Induced Bone Loss [Seite 32]
3.3.1.2 - 2.1.2 Scl-Ab in Bone Mechanical Strength [Seite 32]
3.3.1.3 - 2.1.3 Scl-Ab in Bone Fracture Healing [Seite 33]
3.3.1.4 - 2.1.4 Scl-Ab in Osteogenesis Imperfecta [Seite 33]
3.3.1.5 - 2.1.5 Potential Side Effect [Seite 34]
3.3.2 - 2.2 Dkk1-Ab [Seite 35]
3.4 - References [Seite 36]
4 - Osteocytes and Bone Regeneration [Seite 44]
4.1 - Abstract [Seite 44]
4.2 - 1 Introduction [Seite 44]
4.3 - 2 Bone Matrix Repair by Osteocytes [Seite 45]
4.3.1 - 2.1 Osteocyte Apoptosis and Bone Matrix Microdamage [Seite 46]
4.3.2 - 2.2 Mechanisms of Osteocyte Mediated Matrix Repair [Seite 47]
4.3.2.1 - 2.2.1 RANKL Mediated Osteoclastogenesis [Seite 47]
4.3.2.2 - 2.2.2 Osteocyte Induction of Angiogenesis [Seite 47]
4.3.2.3 - 2.2.3 Osteocytic Osteolysis [Seite 48]
4.3.2.4 - 2.2.4 Osteocyte Control of Bone Matrix Mineralisation [Seite 49]
4.4 - 3 Osteocytes in Fracture [Seite 50]
4.5 - 4 Osteocytes as Regulators of Bone Formation [Seite 51]
4.6 - 5 Summary [Seite 53]
4.7 - References [Seite 53]
5 - Skeletal Stem Cells for Bone and Cartilage Tissue Regeneration [Seite 58]
5.1 - Abstract [Seite 58]
5.2 - 1 Bone Marrow Microenvironment and Bone Marrow Stem Cells [Seite 59]
5.3 - 2 MSCs: Road to Clinical Use [Seite 60]
5.3.1 - 2.1 MSC Homing to Injured Tissues [Seite 60]
5.4 - 3 Specific Uses of BMSCs in Skeletal Regeneration [Seite 62]
5.4.1 - 3.1 Fractures and Bone Defects [Seite 62]
5.4.2 - 3.2 Osteoporosis [Seite 63]
5.4.3 - 3.3 Cartilage Repair and Rheumatic Diseases [Seite 63]
5.5 - 4 Concluding Remarks [Seite 64]
5.6 - References [Seite 65]
6 - Manipulation of Macrophages to Enhance Bone Repair and Regeneration [Seite 69]
6.1 - Abstract [Seite 69]
6.2 - 1 Introduction [Seite 69]
6.3 - 2 Role of Inflammation in Bone Healing [Seite 70]
6.4 - 3 Impact of Chronic Inflammation on Bone Healing [Seite 72]
6.5 - 4 Macrophage Polarization as a Potential Therapeutic Strategy [Seite 74]
6.6 - 5 Strategies to Actively Manipulate Macrophage Behavior [Seite 76]
6.6.1 - 5.1 Cell Delivery [Seite 77]
6.6.2 - 5.2 Drug and Protein Delivery [Seite 78]
6.6.3 - 5.3 Physical Modification of Scaffold Properties [Seite 79]
6.6.4 - 5.4 Selectively Delivery to Macrophages Using Nanoparticles [Seite 80]
6.7 - 6 Conclusions [Seite 81]
6.8 - References [Seite 82]
7 - Cartilage Regeneration Using Induced Pluripotent Stem Cell Technologies [Seite 89]
7.1 - Abstract [Seite 89]
7.2 - 1 The Structure and Limited Repair Capacity of Cartilage [Seite 89]
7.3 - 2 Cell Transplantation into Articular Cartilage Defects [Seite 91]
7.4 - 3 The Use of iPSC-Derived Chondrocytes [Seite 92]
7.4.1 - 3.1 Generation of iPSCs [Seite 92]
7.4.2 - 3.2 Improvement of the Safety of iPSCs [Seite 94]
7.4.3 - 3.3 Transplantation of iPSC-Derived Chondrocytes into Articular Cartilage Defects of Patients [Seite 94]
7.4.4 - 3.4 Development of an iPSC Library [Seite 96]
7.5 - 4 Use of Chondrogenic Cells Generated by Direct Conversion [Seite 96]
7.5.1 - 4.1 Cell-Type Conversion Without the Need for iPS Cells [Seite 96]
7.5.2 - 4.2 Direct Conversion of Dermal Fibroblasts into Chondrogenic Cells [Seite 97]
7.6 - 5 Conclusions [Seite 98]
7.7 - References [Seite 99]
8 - Alveolar Augmentation: Focus on Growth Factors (BMPs) [Seite 103]
8.1 - Abstract [Seite 103]
8.2 - 1 Introduction [Seite 104]
8.3 - 2 Alveolar Augmentation [Seite 106]
8.4 - 3 Clinical Modeling [Seite 109]
8.5 - 4 Alternative Carrier Technologies [Seite 110]
8.6 - 5 rhBMP-2 Coated Dental Implants [Seite 112]
8.7 - 6 Alveolar Augmentation in Clinical Settings [Seite 114]
8.8 - References [Seite 118]
9 - Bone-Biomimetic Biomaterial and Cell Fate Determination [Seite 123]
9.1 - Abstract [Seite 123]
9.2 - 1 Introduction [Seite 124]
9.3 - 2 Biomaterial Design for Bone Regeneration [Seite 125]
9.3.1 - 2.1 Designs to Mimic Physical Characteristics of Bone [Seite 125]
9.3.1.1 - 2.1.1 Designs to Mimic Architecture of Bone [Seite 125]
9.3.1.2 - 2.1.2 Designs to Mimic Topography of Bone [Seite 126]
9.3.1.3 - 2.1.3 Designs to Mimic Mechanical Properties of Bone [Seite 127]
9.3.2 - 2.2 Designs to Mimic Chemical Composition of Bone [Seite 129]
9.3.2.1 - 2.2.1 Designs to Mimic Organic Phase of Bone [Seite 129]
9.3.2.2 - 2.2.2 Designs to Mimic Mineral Phase of Bone [Seite 131]
9.4 - 3 Mechanisms of Cell Fate Determination by Bone-Biomimetic Biomaterial [Seite 132]
9.4.1 - 3.1 Protein Adsorption [Seite 133]
9.4.2 - 3.2 Integrin Signalling [Seite 134]
9.4.2.1 - 3.2.1 Integrin Downstream Signalling Pathways [Seite 136]
9.4.2.1.1 - ERKMAPK Signalling Pathway [Seite 136]
9.4.2.1.2 - RhoROCK Signalling Pathway [Seite 137]
9.4.2.1.3 - PI3K-Akt Signalling Pathway [Seite 138]
9.4.2.2 - 3.2.2 Crosstalk Between Integrin and Growth Factor Signalling [Seite 139]
9.5 - 4 Summary, Conclusion and Perspectives [Seite 139]
9.6 - References [Seite 140]
10 - Biomimetic Scaffolds for Craniofacial Bone Tissue Engineering: Understanding the Role of the Periosteum in Regeneration [Seite 151]
10.1 - Abstract [Seite 151]
10.2 - 1 Introduction [Seite 152]
10.3 - 2 The Role of the Periosteum in Bone Development and Regeneration [Seite 154]
10.3.1 - 2.1 Periosteal Involvement in Wound Healing Initiation [Seite 154]
10.3.2 - 2.2 BMP Signaling [Seite 154]
10.3.3 - 2.3 Hedgehog Signaling [Seite 155]
10.3.4 - 2.4 Wnt Signaling [Seite 156]
10.3.5 - 2.5 Periosteal Cell Recruitment and Function [Seite 156]
10.3.6 - 2.6 Vascularization and Extracellular Environment [Seite 156]
10.4 - 3 Tissue Engineered Electrospun Hydroxyapatite Containing Chitosan Scaffolds [Seite 157]
10.4.1 - 3.1 Key Features of Tissue Engineered Bone Scaffolds [Seite 157]
10.4.2 - 3.2 Electrospinning and Scaffold Fabrication [Seite 158]
10.4.3 - 3.3 HA Containing Chitosan Scaffolds are Osteoinductive [Seite 160]
10.4.4 - 3.4 HA Containing Chitosan Scaffolds are OsseointegrativeOsteoconductive [Seite 161]
10.4.5 - 3.5 Conclusions [Seite 164]
10.5 - References [Seite 165]
11 - Biomaterials Used for Maxillofacial Regeneration [Seite 170]
11.1 - Abstract [Seite 170]
11.2 - 1 Introduction [Seite 170]
11.3 - 2 Current Clinical Treatments for Maxillofacial Bone Regeneration [Seite 171]
11.3.1 - 2.1 Bone Grafting [Seite 171]
11.3.1.1 - 2.1.1 Autografts [Seite 171]
11.3.1.2 - 2.1.2 Allografts [Seite 172]
11.3.1.3 - 2.1.3 Xenografts [Seite 173]
11.3.2 - 2.2 Distraction Osteogenesis [Seite 173]
11.3.3 - 2.3 Guided Bone Regeneration [Seite 174]
11.4 - 3 The Biomaterials Used for Maxillofacial Bone Regeneration [Seite 174]
11.4.1 - 3.1 Biomaterials Clinically Used for Maxillofacial Regeneration [Seite 174]
11.4.2 - 3.2 Recent Advances in Biomaterials Used for Maxillofacial Regeneration [Seite 176]
11.4.2.1 - 3.2.1 Structural Design [Seite 177]
11.4.2.1.1 - Nanotechnology [Seite 177]
11.4.2.1.2 - CADCAM Technique [Seite 180]
11.4.2.2 - 3.2.2 Bioinorganics [Seite 182]
11.4.2.2.1 - Magnesium [Seite 182]
11.4.2.2.2 - Strontium [Seite 182]
11.4.2.2.3 - Zinc [Seite 183]
11.4.2.2.4 - Copper [Seite 184]
11.4.2.2.5 - Lithium [Seite 184]
11.4.2.3 - 3.2.3 Angiogenesis [Seite 185]
11.5 - 4 Summary and Future Directions [Seite 186]
11.6 - References [Seite 187]
12 - Advances and Applications of Nanomechanical Tools in Cartilage Tissue Engineering [Seite 194]
12.1 - Abstract [Seite 194]
12.2 - 1 Introduction [Seite 195]
12.3 - 2 Heterogeneity of Native Cartilage at a Hierarchy of Length Scales [Seite 197]
12.4 - 3 Current Advances in Nanomechanical Methods [Seite 199]
12.4.1 - 3.1 AFM-Based Nanoindentation [Seite 199]
12.4.2 - 3.2 AFM-Based Force Spectroscopy and Imaging [Seite 202]
12.4.3 - 3.3 Other Nanomechanical Techniques [Seite 203]
12.4.4 - 3.4 Multiscale Modeling [Seite 203]
12.5 - 4 Applications of Nanomechanics to Cartilage Tissue Engineering [Seite 204]
12.5.1 - 4.1 Effects of Cytokines on Chondrocyte Synthesis [Seite 204]
12.5.2 - 4.2 Effects of Mechanical Loading on Chondrocyte Synthesis [Seite 206]
12.5.3 - 4.3 Engineered Aggrecan by Bone Marrow Stromal Cells [Seite 207]
12.5.4 - 4.4 Engineered Tissue by Induced Pluripotent Stem Cells [Seite 210]
12.5.5 - 4.5 Chondrogenesis Differentiation of Adipose-Derived Stem Cells [Seite 211]
12.6 - 5 Summary and Future Outlook [Seite 212]
12.7 - References [Seite 213]
13 - Signalling Pathways in Osteochondral Defect Regeneration [Seite 222]
13.1 - Abstract [Seite 222]
13.2 - 1 Introduction [Seite 222]
13.3 - 2 Definition of the Osteochondral Unit and Osteochondral Defects [Seite 223]
13.4 - 3 Principles of Tissue Regeneration in Osteochondral Defects [Seite 225]
13.4.1 - 3.1 Cartilage Regeneration in Osteochondral Defects [Seite 225]
13.4.2 - 3.2 Bone Regeneration in Osteochondral Defects [Seite 227]
13.4.3 - 3.3 Interplay Between Cartilage and Bone Regeneration in Osteochondral Defects [Seite 227]
13.5 - 4 Conclusions [Seite 228]
13.6 - References [Seite 229]
14 - Polymer-Assisted Cartilage and Tendon Repair [Seite 232]
14.1 - Abstract [Seite 232]
14.2 - Abbreviation List [Seite 233]
14.3 - 1 Introduction [Seite 233]
14.3.1 - 1.1 Unmet Medical Need [Seite 234]
14.4 - 2 Articular Cartilage [Seite 235]
14.5 - 3 Healing in Cartilage [Seite 236]
14.6 - 4 Tendons and Healing Tendon [Seite 237]
14.7 - 5 Reconstruction of Articular Cartilage and Tendon-to-Bone Interface [Seite 239]
14.7.1 - 5.1 Articular Cartilage-to-Bone Interface [Seite 239]
14.7.1.1 - 5.1.1 Fibrocartilaginous Enthesis [Seite 239]
14.8 - 6 Cell Sources and Properties [Seite 240]
14.9 - 7 Expansion of Chondrocytes and Tenocytes for TE [Seite 241]
14.10 - 8 Polymers for Cartilage and Tendon TE [Seite 242]
14.10.1 - 8.1 Natural Polymers [Seite 242]
14.10.1.1 - 8.1.1 Collagen [Seite 242]
14.10.1.2 - 8.1.2 Silk and Chitosan [Seite 243]
14.10.1.3 - 8.1.3 Decellularized Extracellular Matrices [Seite 243]
14.11 - 9 Synthetic Polymers [Seite 244]
14.12 - 10 Polymer-Based Hydrogels for TE [Seite 245]
14.12.1 - 10.1 Cartilage [Seite 245]
14.12.2 - 10.2 Tendon [Seite 245]
14.13 - 11 HybridBiphasic Scaffolds [Seite 246]
14.13.1 - 11.1 Cartilage [Seite 246]
14.13.2 - 11.2 Tendon [Seite 246]
14.14 - 12 Tools to Optimize Culture Conditions for Cartilage and Tendon TE [Seite 246]
14.14.1 - 12.1 Cell Numbers [Seite 246]
14.14.2 - 12.2 Seeding Conditions [Seite 247]
14.14.3 - 12.3 Growth Factors in TE [Seite 247]
14.14.3.1 - 12.3.1 Growth Factors for Tendon TE [Seite 247]
14.14.3.2 - 12.3.2 Growth Factors for Cartilage TE [Seite 248]
14.15 - 13 Polymer Topology [Seite 248]
14.16 - 14 Conclusion: Future Challenges [Seite 249]
14.17 - References [Seite 250]