cortical bone 54, CPCs, see calcium phosphate cements cytocompatibility , , 291 cytokines 28, 30, 292

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1 Index ACL, see anterior cruciate ligament AFM, see atomic force microscope anterior cruciate ligament (ACL) 309, 315 anterior pituitary apatite crystals 7, 53, 131, 135 apatite formation, in vitro 120, , 127, 129, 131, 133, 135 apatite nanocrystals 47, 49, 59 60, apatite nanoparticles 49, 62, 65, apatites 47 50, 61 66, 107, , , 137, 195 articular cartilage 146, 163, , 287 atomic force microscope (AFM) 51, 53, 57 autologous bone grafts 182 axons , 223, 226, 228 bacterial nano-cellulose (BNC) , 168, 170 bioactive materials 110, 122 bioartificial endocrine organs biochemical gradients 30 31, 33, 35 biocompatible nanobiomaterials 11 biological apatites 47, 57 59, 61, 63, , 131 biological systems 3, 48 49, 51, 53, 55, 57, 119, 189, 287, 341 biomaterial delivery systems 292 biomaterial design strategies 29 biomaterial functionalization 25 biomaterial handling 379 biomaterial implantation 28 biomaterial matrix 227 biomaterial nanotopography 289 biomaterial reabsorption, complete 326 biomaterials bone-implantable 68 ceramic 99 implanted 28, 66, 224 innovative bone substitute 66 load-bearing 64 nanostructured 65 natural 24, 378 protein-based 285 regenerative 110 smart 307, 313 specialized 247 stiff 286

2 390 Index biomimetic apatite , 124, 129, , 195, 290 biomimetic apatite nanocrystals 60 biomimetic bone substitutes 341 biomimetic materials 250, 307, 315, 336, , 349 smart 307, 315 biomimetics 2 3, 5, 11 12, 15, 64, 228, 230, 290, , 315, 325, 330, 341, 343 biomorphic transformations 99 bionanocomposites 2 3 biopolymers 2, 23, 149, 152, 158, 161, 170 bisphosphonates 66 67, 102 blood vessels 54, 57, 68, 91, 93, 146, 180, 215, 218, 223, 227, 367 BMPs, see bone morphogenetic proteins BMSCs, see bone marrow stem cells BNC, see bacterial nano-cellulose bone alveolar 9, 55 autologous 337 cancellous 23, 54, 151, 181 iliac 337, 339 mammalian 64, 132 mineral 11, 103 osteoporotic 105, 109 bone allografts 182 bone apatite 52, , 137 biological 120, 137 bone augmentation 64, 105 bone cells 4, 33, 89, 344 immature 33 bone cements bone defects 13, 64, 100, 182, 187, 191, bone distraction 91, 313 bone grafts 91, 182, 340, 348 homologous 91, 328 bone graft substitutes 65, 180 bone growth 110, 344 bone loss 4, 101 bone marrow 14, 146, 228, 312, 325, 337 bone marrow cells 349 bone marrow stem cells (BMSCs) 94, 184, 287, 347 bone mineral 6, 344 bone mineral crystals 59 bone mineralization 103 bone morphogenetic proteins (BMPs) 50, 66 67, 92, 213, 243, 290, 341, bone regeneration 4, 47 48, 50, 52, 54, 56, 58, 60, 62 70, 89 91, 137, 152, 180, 182, 184 bone remodeling 66, 87 bone repair 11, 89, 179, 182, 295 bone replacement 286, 291 bone resorption 10, 102 bone scaffolding 98, 110 bone scaffolds 4, 93 ceramic 12 regenerative 4 bone sialoprotein 50, 342 bone substitutes 288, 336, 342, 347 bone tissue 4 5, 32, 86 87, , 147, 154,

3 Index , 195, 288, 290, 313, 335, 340, , 349 developing 346 homologous 335 in-growing 188 bone tissue biomimesis 290 bone tissue engineering 181, 183, 185 bone tissue formation 8, 325 bone tissue growth 199 bone tissue in-growth 188 bone tissue regeneration 10, 47, 92, 179, 199 controlled 294 bone trabeculae 86 calcifications 48 49, 57 58, 343 pathological 49, calcium 9, 11, 52, 58, 97 98, 109, 121, 129, 152, 159, 181, 286, 343 calcium phosphate cements (CPCs) , , 342, calcium phosphates 48, 98, 107, , , 183, 346 CAMs, see cell adhesion molecules CaP biomaterials CaP nanoparticles carbonated hydroxy apatite (CHA) 120, 122, 126, 132 cardiac hypertrophy 261, 267, 273 cardiomyocytes , 267, 272 cartilage 1, 6, 9, 12, , 149, 151, , , 306, 313, 315, , 330, cell adhesion 25, 93, 99, 109, 186, , , 292, 294, , 345 cell adhesion molecules (CAMs) 25, 213, 227, 362 cell biomaterial communication 291 cell material interactions 24, 288 cells anterior pituitary bone-related 65 bone tumor 65 glial 213 osteoblast 6, 8, 86, 195 parathyroid 365 cellular biomaterial interaction 292 ceramic materials 94, 165, 183, , 345 CG, see collagen-gag CHA, see carbonated hydroxy apatite chondrocytes 8, 146, 163, 165, 186, 243 collagen 5 7, 9 10, 12, 50 51, , , , , , 289, 312, , , , mineralized 51, 54 collagen fibers 5 7, 9, 135, , 348 collagen fibrils 50, 52, 121, 163, 287 collagen-gag (CG) 250

4 392 Index cortical bone 54, CPCs, see calcium phosphate cements cytocompatibility , , 291 cytokines 28, 30, 292 DBM, see demineralized bone matrix DEJ, see dentin-enamel junction demineralized bone matrix (DBM) 348 dentin 9, dentine 2, 9, dentin-enamel junction (DEJ) DMEM, see Dulbecco s modified Eagle s medium dorsal root ganglia (DRG) DRG, see dorsal root ganglia Dulbecco s modified Eagle s medium (DMEM) 154, , ECM, see extra cellular matrix ECM proteins 26, , 245, 288 EGF, see epidermal growth factor electrospinning 242, 244, coaxial 229, embryonic development , 361 embryonic stem cells (ESCs) 26, 358, 365 endocrine organs 358, 361, , 378 endoneurial tubes , endoneurium , 223 endothelial cells , 215, 217, 226, 251, 363 endothelial outgrowth cells (EOCs) 189 EOCs, see endothelial outgrowth cells epidermal growth factor (EGF) 292 ESCs, see embryonic stem cells extra cellular matrix (ECM) 22 24, 27 28, 147, , 213, 225, 243, 284, 288, 308 FGF, see fibroblast growth factor fibrils 23, 52, 54, 158, 160, , 170, 288 mineralized fibroblast growth factor (FGF) 213, 292, 348 fibroblasts 28, 186, , 215, 217, 349, 363 fibrosis fractures 55, 91, 101, , 121, 246, 313, 340 vertebral compression 102, 104 gelling agents 148, genes 71, 187, 362 gene therapy 15, 336, 341, 347, 349

5 Index 393 GFs, see growth factors giant cells 29, 309 graphene 274 growth factors (GFs) 23, 25 27, 30 32, 34, 36, 66 67, 186, , , , 244, , 250, 292, hard tissue regeneration 14, 295 heart 180, , 266, heart failure , 262 human blood plasma 120, , 125, 127, 135, 137, 186 human bone morphogenetic proteins 242 hyaluronic acid 7, 27, 151, , 159, , 168, 170, 246, 287, , 348, 359 hydrogels 7, 27, 152, 158, 167, 170, 246, hydrolyses hydroxyapatite 8, 10, 56, 70, 94, 147, 150, 153, 157, 165, 170, 286, 323, 336, hydroxyapatite crystals 56 hydroxyapatite nanocrystals 182, 185, 290 ionotropic gelation , , , 167, 323 lesions 284, 312, 322, leukocytes 28, 34 liver 11, 295, , 375 macrophage phenotype 29 macrophages 28 29, 109, 226 magnesium 6, 129, , 343 magnetic nanoparticles 13 14, , 192, 194, 198, 293 magnetic resonance imaging (MRI) 11, , 322, magnetic scaffolds 12, 159, , 187, , 193, , nanocomposite 192, 198 magnetism 13, 180, 187, 189, 191 magnetite 11, , 295 mechanotransduction 182 meniscal tissue regeneration 311, 315 mesenchymal stem cells (MSCs) 14, 65, , , 165, , 184, 194, 228, 289, 322 mesoporous silica nanoparticles (MSNs) 36, 248 metalloproteinase 28, 348 microrna 260, , 267, 269, 273 MicroRNA-based therapy , 262, 264, 266, , 272, 274 mimicking 9, 33, , 291, 294, 366, 368

6 394 Index mimicry 22 23, 25, 27, 29, 225, , 249 mirna MRI, see magnetic resonance imaging mrna 265, MSCs, see mesenchymal stem cells MSNs, see mesoporous silica nanoparticles multi-functional hard tissues 5, 7, 9 myelination , 226, 228 myocardium , myofibroblasts , 272 nano-apatites 47 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70 nanobiomagnetism 1 2, 4, 6, 8, nanocomposites 2, 186, 197 nanocrystalline apatites 48 49, 58 61, 63 64, 66 nanopores nanosized apatites 62, 65 natural biochemical gradients , 249 natural bone 3, 159, 185, 314 NCPs, see non-collagenous proteins nerve growth factor (NGF) 213, , 229 nerve regeneration 149, , 215, , , nerve regenerative templates , 225, 227, 229 neural guides neurons , 217 neurotmesis , 221 surgical approaches to NGF, see nerve growth factor niomaterials, apatite-based 64 non-collagenous proteins (NCPs) 50 organic polymers 295 organomorphic principle 361, 366, organomorphic scaffoldbioreactor unit 366, 378 osteoarthritis 146, 283, 309 osteoblasts 50, 54, 57, 65, 87, , 108, 137, 182, , 294, 342, 344, 347, 349 osteochondral defects , 151, , 199, 242, 311, 323 osteochondral regeneration 7, 283, 312, 325, 327, 329 osteochondral scaffolds 3, 312, 324, nanostructured collagen-hydroxyapatite 325 osteoclasts 50, 54, 86 87, 102, 109, 182, 342, 344 osteogenesis 92, 184, osteoinductive materials osteointegration osteons 51, 54 osteoporosis 10, 90, , 108, 344 osteoporosis-related fractures 101, 103, 105, 107

7 Index 395 osteotomy 91, 313, 330 pancreatic islets PDGF, see platelet-derived growth factor perineurium , 218, 223 peripheral nerve regeneration 230 peripheral nerves , 223, 227, 230 peripheral nervous system platelet-derived growth factor (PDGF) 229, platelet-rich-plasma (PRP) 92, 242, PLGA 31 32, 35, 183, 249, 286 PLGA microspheres 31 PLGA-pSi 35 36, pri-mirnas progenitor cells 1, 250, 322, 363 protein adsorption 29, 345 protein-biomaterial systems 244 proteins non-collagenous 50 non-collagenous bone 50 reporter 249 protein stability 32 PRP, see platelet-rich-plasma psi particles pulsed electromagnetic fields 12 recellularization , 378 red blood cells SBF, see simulated body fluid SBF solutions 122, 125, 127, , 137 scaffold architecture , 294 scaffold bioactivity 184, 197 scaffold design 288 scaffold fabrication 159, 379 scaffold fixation 192 scaffolds biomimetic 5, 9 11, 247, 250, , 316, 342 biphasic , 150, , 160, 163, , 287 bilayered 199, 287 bio-inspired 5, 7, 9 bioactive 64, 243 biocompatible 358, 365 biological 308 bioresorbable 181 collagen biomaterial 250 fiber-deposited fibre-reinforced 163, 167 fibrous 225 hybrid 12, 64 monolithic 147, 151, 157, 170 monophasic 151, nerve scaffolds organomorphic 358, 367, 369, 371, 373, 375, 377 osteoconductive 11 polycaprolactone 244 polyurethane 311, 315 synthetic 90, 308 three-dimensional 247, 341 tissue-engineered 192, 246 tubular 190 Schwann cells , 224, exogenous

8 396 Index immature mature 214 migrating 226, 228 nonmyelinating 214 Schwann precursor cells 213 signaling molecules 27, simulated body fluid (SBF) 120, , 127, 129, , , 186 smart biomimetic biomaterials 306 SMFs, see static magnetic field spinal fusion 12, 293, , 339 spinal surgery 64, 314, 316, , 338, 340, 342, 344, 346, 348, 350 spine 102, spongy bone 87, 96, 181, 290 static magnetic field (SMFs) 13, 189, stem cells 147, 228, 312, 347 adult bone marrow 347 cultured bone marrow 94 embryonic 358 human mesenchymal , 170, 194 mesenchymal 14, 65, , 289 multipotent 373 neural crest 216 stromal cells, human bone marrow 189 stromal/vascular scaffold (SVS) , , , 373, 376, 378 strontium , 344 SVS, see stromal/vascular scaffold synthetic biomaterials 25, 29, 220, 349, 358, 378 tendons 87, 145, 184, 306, 308, 313, 315, therapeutic agents 66, , 274 thymus 376, 378 thyrocytes , 374 thyroid , 366, 371, 374 thyroid cells , 374 tissue cardiac 273 cartilage 146, 154, 157, 159, 163, 284, 323 cartilage repair 288, human bone 135 ligament 88 musculoskeletal natural bone 98 nerve 220, 229 skeletal 57 stromal 219, 223 vascular 13, 190, 363 tissue engineering strategies , 345 tissue regeneration 4, 10, 22, 30, 147, 181, 221, 243, 246, 284, 288, tissue repair 213, 216, 315 tissue transplantation titanium 65, , 131, 339 tooth 1, trabecular bone 98, 193, 287 tumors 68 70, 180, , 198 vascular endothelial growth factor (VEGF) 67, 180,

9 Index , 227, 229, 244, 251, 292, vascularization 181, 183, 219, , , 286, 307 VEGF, see vascular endothelial growth factor vertebroplasty Wallerian degeneration , 219 wound healing 23, 28, 30, 245 X-ray diffraction (XRD) 51, 53, 62, 109 XRD, see X-ray diffraction

10

11 This book presents a wide and interdisciplinary overview of the current state of the art in the development of biomimetic materials for tissue regeneration on the basis of relevant and high-impact clinical needs. It specifically emphasizes the regeneration of bone, cartilage, and osteochondral tissues as well as soft tissues such as nerves, heart, and endocrine organs. It brings together contributions from materials scientists, biologists, and surgeons with globally recognized experience in the field of regenerative medicine. The aim of the book is to highlight the relevance of biomimetics as an elective approach for the development of new scaffolds that can direct regenerative cascade by means of chemico-physical and topological nanocues presented to cells and biologic tissues. Particularly, the book refers to emerging concepts in synthesis processes and scaffolds inspired by nature as well as to novel approaches for smart functionalization such as the use of magnetic signaling. Anna Tampieri is director of CNR Institute of Science and Technology for Ceramics, Italy, and head of the Department of Bio-ceramics and Bio-hybrid Composites for Regenerative Medicine since She is the coordinator of several European projects and scientific advisor to several companies active in the biomedical and pharmaceutical fields. Dr. Tampieri is also the organizer of several international conferences and symposia on biomaterials. V483 ISBN Sprio Tampieri Simone Sprio is a researcher at the Department of Bio-ceramics and Bio-hybrid Composites for Regenerative Medicine, CNR Institute of Science and Technology for Ceramics, since He is active in the field of research and development of new ceramic-based biomaterials and devices for bone regeneration in orthopedics and spinal, maxillofacial, and neurosurgery. Bio-Inspired Regenerative Medicine This well-written book is essential reading for professionals and students from materials science, materials engineering, biology, or medicine who wish to know the state of the art on biomimetic-inspired materials for surgical applications. All fields are clearly presented, from powder synthesis to scaffold processing, tissue engineering, interaction between biomaterials and living cells, and biomechanical behavior. It is a good reference point for the foreseeable future. Prof. Anne Leriche University of Valenciennes, France Bio-Inspired Regenerative Medicine Materials, Processes, and Clinical Applications edited by Simone Sprio Anna Tampieri