Bone biomaterials and interactions with stem cells

Abstract

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues: (1) developing ideal biomaterials with a combination of suitable biological and mechanical properties; (2) constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and (3) inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Typical bone biomaterials that have been developed, including bioactive ceramics, biodegradable polymers, and biodegradable metals, are reviewed, with an emphasis on their characteristics and applications. The necessary porous structure of bone biomaterials for the cell microenvironment is discussed, along with the corresponding fabrication methods. Additionally, the promising seed stem cells for bone repair are summarized, and their interaction mechanisms with bone biomaterials are discussed in detail. Special attention has been paid to the signaling pathways involved in the focal adhesion and osteogenic differentiation of stem cells on bone biomaterials. Finally, achievements regarding bone biomaterials are summarized, and future research directions are proposed.

Bone repair: Building better bone grafts

A review of bone repair biomaterials highlights the best materials available and examines their interactions with stem cells. Bone structure is complex, with a crystalline outer layer for strength, and a spongy interior where blood flows and new red blood cells are made. Developing strong, biocompatible materials that mimic this structure and promote new bone growth is challenging. Cijun Shuai at Central South University in China and co-workers have published a review summarizing recent advances and indicating promising research directions. The review highlights materials that: provide the best combination of strength and flexibility; contain pores of many sizes from nano- to microscale, similar to bone; biodegrade at the same rate as new bone grows; and provide an optimal environment for stem cells to attach and then differentiate into bone cells.

References

[1] Lu H, Liu Y, Guo J, et al Biomaterials with antibacterial and osteoinductive properties to repair infected bone defects. Int J Mol Sci, 2016, 17: 334

[2] Maksimkin AV, Senatov FS, Anisimova NY et al. Multilayer porous UHMWPE scaffolds for bone defects replacement. Mater Sci Eng C Mater Biol Appl, 2017, 73: 366-372

[3] Terranova L, Mallet R, Perrot R et al. Polystyrene scaffolds based on microfibers as a bone substitute; development and in vitro study. Acta Biomater, 2016, 29: 380-388

[4] Klein-Nulend J, van Oers RF, Bakker AD et al. Nitric oxide signaling in mechanical adaptation of bone. Osteoporos Int, 2014, 25: 1427-1437

[5] Montazerolghaem M, Rasmusson A, Melhus H et al. Simvastatin-doped pre-mixed calcium phosphate cement inhibits osteoclast differentiation and resorption. J Mater Sci Mater Med, 2016, 27: 83

[6] Yang F, Wang J, Hou J et al. Bone regeneration using cell-mediated responsive degradable PEG-based scaffolds incorporating with rhBMP-2. Biomaterials, 2013, 34: 1514-1528

[7] Shadjou N, Hasanzadeh M. Bone tissue engineering using silica-based mesoporous nanobiomaterials: recent progress. Mater Sci Eng C Mater Biol Appl, 2015, 55: 401-409

[8] Ishack S, Mediero A, Wilder T et al. Bone regeneration in critical bone defects using three-dimensionally printed β-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2. J Biomed Mater Res B Appl Biomater, 2017, 105: 366-375

[9] Bian L, Mak AFT, Wu C et al. A model for facilitating translational research and development in China: call for establishing a Hong Kong Branch of the Chinese National Engineering Research Centre for Biomaterials. J Orthop Transl, 2014, 2: 170-176

[10] Wang C, Wang S, Li K et al. Preparation of laponite bioceramics for potential bone tissue engineering applications. PLoS One, 2014, 9: e99585

[11] Simpson AH, Murray IR. Main differences in osteoporotic fracture models: which should I use? Injury, 2016, 47 Suppl 1 S15-S20

[12] Andric T, Sampson AC, Freeman JW. Fabrication and characterization of electrospun osteon mimicking scaffolds for bone tissue engineering. Mater Sci Eng C, 2011, 31: 2-8

[13] Yunus BashaR, Sampath Kumar TS, Doble M. Design of biocomposite materials for bone tissue regeneration. Mater Sci Eng C Mater Biol Appl, 2015, 57: 452-463

[14] Goto T, Sasaki K. Effects of trace elements in fish bones on crystal characteristics of hydroxyapatite obtained by calcination. Ceram Int, 2014, 40: 10777-10785

[15] Elias CN, Meyers MA, Valiev RZ et al. Ultrafine grained titanium for biomedical applications: an overview of performance. J Mater Res Technol, 2013, 2: 340-350

[16] Nguyen LH, Annabi N, Nikkhah M et al. Vascularized bone tissue engineering: approaches for potential improvement. Tissue Eng Part B Rev, 2012, 18: 363-382

[17] Mckittrick J, Chen PY, Tombolato L et al. Energy absorbent natural materials and bioinspired design strategies: a review. Mater Sci Eng C, 2010, 30: 331-342

[18] Hanson Ma, Gluckman P. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev, 2014, 94: 1027-1076

[19] Webber MJ, Khan OF, Sydlik SA. A perspective on the clinical translation of scaffolds for tissue engineering. Ann Biomed Eng, 2015, 43: 641-656

[20] Chaudhari AA, Vig K, Baganizi DR et al. Future prospects for scaffolding methods and biomaterials in skin tissue engineering: a review. Int J Mol Sci, 2016, 17: 1974

[21] Kundu J, Pati F, Jeong YH, Gabor F, Wei S et al. Biomaterials for biofabrication of 3D tissue scaffolds. Biofabrication: Micro- and Nano-Fabrication, Printing, Patterning and Assemblies, 2013 William Andrew Waltham 23-46

[22] Gerhardt LC, Boccaccini AR. Bioactive glass and glass-ceramic scaffolds for bone tissue engineering. Materials, 2010, 3: 3867-3910

[23] Comesaña R, Lusquiños F, Del VJ et al. Toward smart implant synthesis: bonding bioceramics of different resorbability to match bone growth rates. Sci Rep, 2015, 5: 10677

[24] Habib FN, Nikzad M, Masood SH et al. Design and development of scaffolds for tissue engineering using three-dimensional printing for bio-based applications. 3D Print Addit Manuf, 2016, 3: 119-127

[25] Liu Y, Kim JH, Young D et al. Novel template-casting technique for fabricating β-tricalcium phosphate scaffolds with high interconnectivity and mechanical strength and in vitro cell responses. J Biomed Mater Res A, 2010, 92: 997-1006

[26] Fedorovich NE, Alblas J, Hennink WE et al. Organ printing: the future of bone regeneration? Trends Biotechnol, 2011, 29: 601-606

[27] Saiz E, Zimmermann EA, Lee JS et al. Perspectives on the role of nanotechnology in bone tissue engineering. Dent Mater, 2013, 29: 103-115

[28] Hench LL. The future of bioactive ceramics. J Mater Sci Mater Med, 2015, 26: 86

[29] Kraus KH, Kirkerhead C. Mesenchymal stem cells and bone regeneration. Vet Surg, 2006, 35: 232-242

[30] Kolk A, Handschel J, Drescher W et al. Current trends and future perspectives of bone substitute materials—from space holders to innovative biomaterials. J Cranio Maxill Surg, 2012, 40: 706-718

[31] Kocabey S, Ceylan H, Tekinay AB et al. Glycosaminoglycan mimetic peptide nanofibers promote mineralization by osteogenic cells. Acta Biomater, 2013, 9: 9075-9085

[32] Floren M, Migliaresi C, Motta A. Processing techniques and applications of silk hydrogels in bioengineering. J Funct Biomater, 2016, 7: 26

[33] Fu Q, Saiz E, Rahaman MN et al. Bioactive glass scaffolds for bone tissue engineering: state of the art and future perspectives. Mater Sci Eng C Mater Biol Appl, 2011, 31: 1245-1256

[34] Wagoner Johnson AJ, Herschler BA. A review of the mechanical behavior of CaP and CaP/polymer composites for applications in bone replacement and repair. Acta Biomater, 2011, 7: 16-30

[35] Zreiqat H, Ramaswamy Y, Wu C et al. The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering. Biomaterials, 2010, 31: 3175-3184

[36] Bosco R, Beucken JVD, Leeuwenburgh S et al. Surface engineering for bone implants: a trend from passive to active surfaces. Coatings, 2012, 2: 95-119

[37] Bose S, Vahabzadeh S, Bandyopadhyay A. Bone tissue engineering using 3D printing. Mater Today, 2013, 16: 496-504

[38] Webber MJ, Appel EA, Meijer E et al. Supramolecular biomaterials. Nat Mater, 2016, 15: 13-26

[39] Salinas A, Esbrit P, Valletregi M. A tissue engineering approach based on the use of bioceramics for bone repair. Biomater Sci, 2012, 1: 40-51

[40] Zhang Q, Mochalin VN, Neitzel I et al. Mechanical properties and biomineralization of multifunctional nanodiamond-PLLA composites for bone tissue engineering. Biomaterials, 2012, 33: 5067-5075

[41] Baradaran S, Moghaddam E, Basirun WJ et al. Mechanical properties and biomedical applications of a nanotube hydroxyapatite-reduced graphene oxide composite. Carbon, 2014, 69: 32-45

[42] Wang C, Shen H, Tian Y et al. Bioactive nanoparticle-gelatin composite scaffold with mechanical performance comparable to cancellous bones. ACS Appl Mater Interfaces, 2014, 6: 13061-13068

[43] Dou Y, Wu C, Chang J. Preparation, mechanical property and cytocompatibility of poly(l-lactic acid)/calcium silicate nanocomposites with controllable distribution of calcium silicate nanowires. Acta Biomater, 2012, 8: 4139-4150

[44] Lvov Y, Abdullayev E. Functional polymer-clay nanotube composites with sustained release of chemical agents. Prog Polym Sci, 2013, 38: 1690-1719

[45] Bose S, Roy M, Bandyopadhyay A. Recent advances in bone tissue engineering scaffolds. Trends Biotechnol, 2012, 30: 546-554

[46] Bose S, Banerjee D, Bandyopadhyay A, Bose S, Bandyopadhyay A. Introduction to biomaterials and devices for bone disorders. Materials and Devices for Bone Disorders, 2016 London Academic Press 1-2

[47] Zheng YF, Gu XN, Witte F. Biodegradable metals. Mater Sci Eng R, 2014, 77: 1-34

[48] Windhagen H, Radtke K, Weizbauer A et al. Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study. Biomed Eng Online, 2013, 12: 62

[49] Mohanapriya S, Mumjitha M, Purnasai K et al. Fabrication and characterization of poly(vinyl alcohol)-TiO2 nanocomposite films for orthopedic applications. J Mech Behav Biomed, 2016, 63: 141-156

[50] Agarwal S, Curtin J, Duffy B et al. Biodegradable magnesium alloys for orthopaedic applications: a review on corrosion, biocompatibility and surface modifications. Mater Sci Eng C Mater Biol Appl, 2016, 68: 948-963

[51] Wen CE, Xiong JY, Li YC et al. Porous shape memory alloy scaffolds for biomedical applications: a review. Phys Scr, 2010, 2010: 561-578

[52] Lin K, Xia L, Li H et al. Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics. Biomaterials, 2013, 34: 10028-10042

[53] Lalwani G, Henslee AM, Farshid B et al. Tungsten disulfide nanotubes reinforced biodegradable polymers for bone tissue engineering. Acta Biomater, 2013, 9: 8365-8373

[54] Wang S, Wang X, Draenert FG et al. Bioactive and biodegradable silica biomaterial for bone regeneration. Bone, 2014, 67: 292-304

[55] Wang J, Witte F, Xi T et al. Recommendation for modifying current cytotoxicity testing standards for biodegradable magnesium-based materials. Acta Biomater, 2015, 21: 237-249

[56] Hench LL. The story of Bioglass®. J Mater Sci Mater Med, 2006, 17: 967-978

[57] Miguez-Pacheco V, Hench LL, Boccaccini AR. Bioactive glasses beyond bone and teeth: emerging applications in contact with soft tissues. Acta Biomater, 2015, 13: 1-15

[58] He C, Jin X, Ma PX. Calcium phosphate deposition rate, structure and osteoconductivity on electrospun poly (L-lactic acid) matrix using electrodeposition or simulated body fluid incubation. Acta Biomater, 2014, 10: 419-427

[59] Eliaz N, Metoki N. Calcium Phosphate bioceramics: a review of their history, structure, properties, coating technologies and biomedical applications. Materials, 2017, 10: 334

[60] Pan YK, Chen CZ, Wang DG et al. Preparation and bioactivity of micro-arc oxidized calcium phosphate coatings. Mater Chem Phys, 2013, 141: 842-849

[61] Duer MJ. The contribution of solid-state NMR spectroscopy to understanding biomineralization: atomic and molecular structure of bone. J Magn Reson, 2015, 253: 98-110

[62] Cheng F, Sun K, Zhao Y et al. Synthesis and characterization of HA/YVO4: Yb3+, Er3+ up-conversion luminescent nano-rods. Ceram Int, 2014, 40: 11329-11334

[63] Feng P, Niu M, Gao C et al. A novel two-step sintering for nano-hydroxyapatite scaffolds for bone tissue engineering. Sci Rep, 2014, 4: 5599

[64] Abidi SSA, Murtaza Q. Synthesis and characterization of nano-hydroxyapatite powder using wet chemical precipitation reaction. J Mater Sci Technol, 2014, 30: 307-310

[65] Xie C, Lu X, Wang K et al. Pulse electrochemical driven rapid layer-by-layer assembly of polydopamine and hydroxyapatite nanofilms via alternative redox in situ synthesis for bone regeneration. ACS Biomater Sci Eng, 2016, 2: 920-928

[66] Shuai C, Li P, Liu J et al. Optimization of TCP/HAP ratio for better properties of calcium phosphate scaffold via selective laser sintering. Mater Charact, 2013, 77: 23-31

[67] Tarafder S, Bose S. Polycaprolactone-coated 3D printed tricalcium phosphatescaffolds for bone tissue engineering: in vitro alendronate release behavior and localdelivery effect on in vivo osteogenesis. ACS Appl Mater Interfaces, 2014, 6: 9955-9965

[68] He F, Qian G, Ren W et al. Fabrication of β-tricalcium phosphate composite ceramic sphere-based scaffolds with hierarchical pore structure for bone regeneration. Biofabrication, 2017, 9: 025005

[69] Bruder SP, Kraus KH, Goldberg VM et al. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg, 1998, 80: 985-996

[70] Elsayed H, Rincón Romero A, Ferroni L et al. Bioactive glass-ceramic scaffolds from novel ‘inorganic gel casting’and sinter-crystallization. Materials, 2017, 10: 171

[71] Maehira F, Miyagi I, Eguchi Y. Effects of calcium sources and soluble silicate on bone metabolism and the related gene expression in mice. Nutrition, 2009, 25: 581-589

[72] Zhou X, Zhang N, Mankoci S et al. Silicates in orthopaedics and bone tissue engineering materials. J Biomed Mater Res A, 2017, 105: 2090-2102

[73] Henstock JR, Canham LT, Anderson SI. Silicon: the evolution of its use in biomaterials. Acta Biomater, 2015, 11: 17-26

[74] Carlisle EM. Silicon: a requirement in bone formation independent of vitamin D1. Calcif Tissue Int, 1981, 33: 27-34

[75] Bose S, Tarafder S, Banerjee SS et al. Understanding in vivo response and mechanical property variation in MgO, SrO and SiO2 doped β-TCP. Bone, 2011, 48: 1282-1290

[76] Midha S, van den Bergh W, Kim TB et al. Bioactive glass foam scaffolds are remodelled by osteoclasts and support the formation of mineralized matrix and vascular networks in vitro. Adv Healthcare Mater, 2013, 2: 490-499

[77] Wu C, Zhai D, Ma H et al. Stimulation of osteogenic and angiogenic ability of cells on polymers by pulsed laser deposition of uniform akermanite-glass nanolayer. Acta Biomater, 2014, 10: 3295-3306

[78] Su CC, Kao CT, Hung CJ et al. Regulation of physicochemical properties, osteogenesis activity, and fibroblast growth factor-2 release ability of β-tricalcium phosphate for bone cement by calcium silicate. Mater Sci Eng C Mater Biol Appl, 2014, 37: 156-163

[79] O'Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today, 2011, 14: 88-95

[80] Lertcumfu N, Jaita P, Manotham S et al. Properties of calcium phosphates ceramic composites derived from natural materials. Ceram Int, 2016, 42: 10638-10644

[81] Padmanabhan SK, Gervaso F, Carrozzo M et al. Wollastonite/hydroxyapatite scaffolds with improved mechanical, bioactive and biodegradable properties for bone tissue engineering. Ceram Int, 2013, 39: 619-627

[82] Mohammadi H, Sepantafar M, Ostadrahimi A. The role of bioinorganics in improving the mechanical properties of silicate ceramics as bone regenerative materials. J Ceram Sci Technol, 2015, 6: 1-8

[83] Wu C, Chang J. A review of bioactive silicate ceramics. Biomed Mater, 2013, 8: 032001

[84] Wu H, Liu G, Wu Q et al. Repairing rabbit radial defects by combining bone marrow stroma stem cells with bone scaffold material comprising a core-cladding structure. Genet Mol Res, 2015, 14: 11933-11943

[85] Wu C, Ramaswamy Y, Zreiqat H. Porous diopside (CaMgSi2O6) scaffold: a promising bioactive material for bone tissue engineering. Acta Biomater, 2010, 6: 2237-2245

[86] Rezaei Y, Moztarzadeh F, Shahabi S et al. Synthesis, characterization, and in vitro bioactivity of sol-gel-derived SiO2-CaO-P2O5-MgO-SrO bioactive glass. Synth React Inorg Met-Org Nano-Met Chem, 2014, 44: 692-701

[87] Vallittu PK, Närhi TO, Hupa L. Fiber glass-bioactive glass composite for bone replacing and bone anchoring implants. Dent Mater, 2015, 31: 371-381

[88] Filipowska J, Pawlik J, Cholewa-Kowalska K et al. Incorporation of sol-gel bioactive glass into PLGA improves mechanical properties and bioactivity of composite scaffolds and results in their osteoinductive properties. Biomed Mater, 2014, 9: 065001

[89] Hench LL. Bioceramics: from concept to clinic. J Am Ceram Soc, 1991, 74: 1487-1510

[90] Jebahi S, Oudadesse H, Jardak N et al. Biological therapy of strontium-substituted bioglass for soft tissue wound-healing: responses to oxidative stress in ovariectomised rats. Ann Pharm Fr, 2013, 71: 234-242

[91] Sepulveda P, Jones JR, Hench LL. Bioactive sol-gel foams for tissue repair. J Biomed Mater Res, 2002, 59: 340-348

[92] He D, Liu P, Liu X et al. Hydroxyapatite bioceramic coatings prepared by hydrothermal-electrochemical deposition method. J Wuhan Univ Technol Mater Sci Ed, 2014, 29: 398-400

[93] Levandowski N, Camargo NH, Silva DF et al. Characterization of different nanostructured bone substitute biomaterials. Adv Mater Res, 2014, 936: 695-700

[94] Ching HA, Choudhury D, Nine MJ et al. Effects of surface coating on reducing friction and wear of orthopaedic implants. Sci Technol Adv Mat, 2014, 15: 014402

[95] Li Z, Munroe P, Jiang Z et al. Designing superhard, self-toughening CrAlN coatings through grain boundary engineering. Acta Mater, 2012, 60: 5735-5744

[96] Li Bao Feng. Design of Sports Field Based on Nanometer Materials. Applied Mechanics and Materials, 2013, 340: 366-369

[97] Chen X, Wang Z, Ding D et al. Strengthening and toughening strategies for tin bronze alloy through fabricating in-situ nanostructured grains. Mater Des (1980-2015), 2015, 66: 60-66

[98] Huang F, Wang Z, Lu X et al. Peculiar magnetism of BiFeO3 nanoparticles with size approaching the period of the spiral spin structure. Sci Rep, 2013, 3: 2907

[99] Sohail MF, Javed I, Hussain SZ et al. Folate grafted thiolated chitosan enveloped nanoliposomes with enhanced oral bioavailability and anticancer activity of docetaxel. J Mater Chem B, 2016, 4: 6240-6248

[100] Wang D, De Cicco MP, Li X. Using diluted master nanocomposites to achieve grain refinement and mechanical property enhancement in as-cast Al-9Mg. Mater Sci Eng A, 2012, 532: 396-400

[101] Tsao L, Wu M, Chang S. Effect of TiO2 nanoparticles on the microstructure and bonding strengths of Sn0.7Cu composite solder BGA packages with immersion Sn surface finish. J Mater Sci Mater Electron, 2012, 23: 681-687

[102] Shuai C, Feng P, Wu P et al. A combined nanostructure constructed by graphene and boron nitride nanotubes reinforces ceramic scaffolds. Chem Eng J, 2017, 313: 487-497

[103] Gao C, Feng P, Peng S et al. Carbon nanotubes, graphene and boron nitride nanotubes reinforced bioactive ceramics for bone repair. Acta Biomater, 2017, 61: 1-20

[104] Vila M, Cicuéndez M, Sánchez-Marcos J et al. Electrical stimuli to increase cell proliferation on carbon nanotubes/mesoporous silica composites for drug delivery. J Biomed Mater Res A, 2013, 101: 213-221

[105] Tatarko P, Grasso S, Chlup Z et al. Toughening effect of multi-walled boron nitride nanotubes and their influence on the sintering behaviour of 3Y-TZP zirconia ceramics. J Eur Ceram Soc, 2014, 34: 1829-1843

[106] Wu C, Xia L, Han P et al. Graphene-oxide-modified β-tricalcium phosphate bioceramics stimulate in vitro and in vivo osteogenesis. Carbon, 2015, 93: 116-129

[107] Zeng X, Ye L, Yu S et al. Facile preparation of superelastic and ultralow dielectric boron nitride nanosheet aerogels via freeze-casting process. Chem Mater, 2015, 27: 5849-5855

[108] Echeberria J, Rodríguez N, Vleugels J et al. Hard and tough carbon nanotube-reinforced zirconia-toughened alumina composites prepared by spark plasma sintering. Carbon, 2012, 50: 706-717

[109] Zhang J, Jia C, Jia Z et al. Strengthening mechanisms in carbon nanotube reinforced bioglass composites. Front Chem Sci Eng, 2012, 6: 126-131

[110] Ahmad I, Islam M, Abdo HS et al. Toughening mechanisms and mechanical properties of graphene nanosheet-reinforced alumina. Mater Des, 2015, 88: 1234-1243

[111] Lahiri D, Singh V, Benaduce AP et al. Boron nitride nanotube reinforced hydroxyapatite composite: mechanical and tribological performance and in-vitro biocompatibility to osteoblasts. J Mech Behav Biomed, 2011, 4: 44-56

[112] Lock J, Nguyen TY, Liu H. Nanophase hydroxyapatite and poly (lactide-co-glycolide) composites promote human mesenchymal stem cell adhesion and osteogenic differentiation in vitro. J Mater Sci Mater Med, 2012, 23: 2543-2552

[113] Huang ZW, Ding TT, Sun J. Study of effect on cell proliferation and hemolysis of HAP and TCP nanometer particles. Adv Mater Res, 2012, 378: 711-714

[114] Zhou Q, Shi L, Chattoraj S et al. Preparation and characterization of surface-engineered coarse microcrystalline cellulose through dry coating with silica nanoparticles. J Pharm Sci, 2012, 101: 4258-4266

[115] Milovac D, Gallego FerrerG, Ivankovic M et al. PCL-coated hydroxyapatite scaffold derived from cuttlefish bone: morphology, mechanical properties and bioactivity. Mater Sci Eng C Mater Biol Appl, 2014, 34: 437-445

[116] Roohani-Esfahani S, Nouri-Khorasani S, Lu Z et al. Effects of bioactive glass nanoparticles on the mechanical and biological behavior of composite coated scaffolds. Acta Biomater, 2011, 7: 1307-1318

[117] Yang K, Feng J, Zhou X et al. In-situ formed γ-Al 2 O 3 nanocrystals repaired and toughened Al 2 O 3 coating prepared by plasma spraying. Surf Coat Technol, 2012, 206: 3082-3087

[118] Zhou F, Ren H, Li G et al. On-line separation and preconcentration of trace cadmium in environmental water samples by micro column filled with modified nanometer Si-HAP prior to FAAS determination. Int J Environ Anal Chem, 2012, 92: 821-831

[119] Kasirajan S, Ngouajio M. Polyethylene and biodegradable mulches for agricultural applications: a review. Agron Sustainable Dev, 2012, 32: 501-529

[120] Zhao Q, Qi HJ, Xie T. Recent progress in shape memory polymer: New behavior, enabling materials, and mechanistic understanding. Prog Polym Sci, 2015, 49-50: 79-120

[121] Hammouche S, Hammouche D, Mcnicholas M. Biodegradable bone regeneration synthetic scaffolds: in tissue engineering. Curr Stem Cell Res Ther, 2012, 7: 134-142

[122] Bezerra CS, de Farias Lemos CMG, de Sousa M et al. Enzyme immobilization onto renewable polymeric matrixes: past, present, and future trends. J Appl Polym Sci, 2015, 132: 42125

[123] Ates O. Systems biology of microbial exopolysaccharides production. Front Bioeng Biotechnol, 2016, 3: 200

[124] Sonia TA, Sharma CP. An overview of natural polymers for oral insulin delivery. Drug Discov Today, 2012, 17: 784-792

[125] Cheneler D, Bowen J. Degradation of polymer films. Soft Matter, 2013, 9: 344-358

[126] Mu HM, Wang LY. Effect of therapeutic ultrasound on brain angiogenesis following intracerebral hemorrhage in rats. Microvasc Res, 2015, 102: 11-18

[127] O’Loughlin A, Kulkarni M, Creane M et al. Topical administration of allogeneic mesenchymal stromal cells seeded in a collagen scaffold augments wound healing and increases angiogenesis in the diabetic rabbit ulcer. Diabetes, 2013, 62: 2588-2594

[128] Su Y, Su Q, Liu W et al. Controlled release of bone morphogenetic protein 2 and dexamethasone loaded in core-shell PLLACL-collagen fibers for use in bone tissue engineering. Acta Biomater, 2012, 8: 763-771

[129] Aljawish A, Chevalot I, Jasniewski J et al. Enzymatic synthesis of chitosan derivatives and their potential applications. J Mol Catal B Enzym, 2015, 112: 25-39

[130] Kyzas GZ, Siafaka PI, Pavlidou EG et al. Synthesis and adsorption application of succinyl-grafted chitosan for the simultaneous removal of zinc and cationic dye from binary hazardous mixtures. Chem Eng J, 2015, 259: 438-448

[131] Rajitha P, Gopinath D, Biswas R et al. Chitosan nanoparticles in drug therapy of infectious and inflammatory diseases. Expert Opin Drug Delivery, 2016, 13: 1177-1194

[132] Seol YJ, Lee JY, Park YJ et al. Chitosan sponges as tissue engineering scaffolds for bone formation. Biotechnol Lett, 2004, 26: 1037-1041

[133] Klokkevold PR, Vandemark L, Kenney EB et al. Osteogenesis enhanced by chitosan (poly-N-acetyl glucosaminoglycan) in vitro. J Periodontol, 1996, 67: 1170-1175

[134] Foldberg S, Petersen M, Fojan P et al. Patterned poly (lactic acid) films support growth and spontaneous multilineage gene expression of adipose-derived stem cells. Colloids Surf B Biointerfaces, 2012, 93: 92-99

[135] Wright B, Parmar N, Bozec L et al. A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres. J Biomater Appl, 2015, 30: 147-159

[136] Flores-Fernández GM, Griebenow K. Glycosylation improves α-chymotrypsin stability upon encapsulation in poly (lactic-co-glycolic) acid microspheres. Results Pharma Sci, 2012, 2: 46-51

[137] Goonoo N, Bhaw-Luximon A, Jhurry D. Biodegradable polymer blends: miscibility, physicochemical properties and biological response of scaffolds. Polym Int, 2015, 64: 1289-1302

[138] Asti A, Gioglio L. Natural and synthetic biodegradable polymers: different scaffolds for cell expansion and tissue formation. Int J Artif Organs, 2014, 37: 187-205

[139] Parisi OI, Curcio M, Puoci F, Puoci F. Polymer chemistry and synthetic polymers. Advanced Polymers in Medicine, 2015 Cham: Springer International Publishing 1-31

[140] Tian H, Tang Z, Zhuang X et al. Biodegradable synthetic polymers: preparation, functionalization and biomedical application. Prog Polym Sci, 2012, 37: 237-280

[141] Orchel A, Jelonek K, Kasperczyk J et al. The influence of chain microstructure of biodegradable copolyesters obtained with low-toxic zirconium initiator to in vitro biocompatibility. Biomed Res Int, 2013, 2013: 176946

[142] de Gracia Lux C, Joshi-Barr S, Nguyen T et al. Biocompatible polymeric nanoparticles degrade and release cargo in response to biologically relevant levels of hydrogen peroxide. J Am Chem Soc, 2012, 134: 15758-15764

[143] Asghari F, Samiei M, Adibkia K et al. Biodegradable and biocompatible polymers for tissue engineering application: a review. Artif Cell Nanomed B, 2017, 45: 185-192

[144] Santos A, Aw MS, Bariana M et al. Drug-releasing implants: current progress, challenges and perspectives. J Mater Chem B, 2014, 2: 6157-6182

[145] Huang QW, Wang LP, Wang JY. Mechanical properties of artificial materials for bone repair. J Shanghai Jiaotong Univ (Sci), 2014, 19: 675-680

[146] Vert M. After soft tissues, bone, drug delivery and packaging, PLA aims at blood. Eur Polym J, 2015, 68: 516-525

[147] Zhou C, Shi Q, Guo W et al. Electrospun bio-nanocomposite scaffolds for bone tissue engineering by cellulose nanocrystals reinforcing maleic anhydride grafted PLA. ACS Appl Mater Interfaces, 2013, 5: 3847-3854

[148] Ma L, Jiang W, Li W. Solvent-free fabrication of tissue engineering scaffolds with immiscible polymer blends. Int J Polym Mater Polym Biomater, 2014, 63: 510-517

[149] Singla R, Mehta R. Preparation and characterization of polylactic acid-based biodegradable blends processed under microwave radiation. Polym Plast Technol Eng, 2012, 51: 1014-1017

[150] Suryanegara L, Nakagaito AN, Yano H. The effect of crystallization of PLA on the thermal and mechanical properties of microfibrillated cellulose-reinforced PLA composites. Compos Sci Technol, 2009, 69: 1187-1192

[151] Zhang X, Shi Z, Fu W et al. in vitro biocompatibility study of electrospun copolymer ethylene carbonate-ɛ-caprolactone and vascular endothelial growth factor blended nanofibrous scaffolds. Appl Surf Sci, 2012, 258: 2301-2306

[152] Larrañaga A, Sarasua J-R. Poly (α-hydroxy acids)-based cell microcarriers. Appl Sci, 2016, 6: 436

[153] Zhao XY, Xie J, Wang MZ et al. Synthesis and characterization of novel biodegradable tetra-amino-terminated PLGA telechelic copolymer. J Mater Sci, 2013, 48: 659-664

[154] Uskoković V, Hoover C, Vukomanović M et al. Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(D, L-lactide-co-glycolide) powders for the treatment of osteomyelitis. Mater Sci Eng C Mater Biol Appl, 2013, 33: 3362-3373

[155] Marrache S, Kumar Pathak R, Darley KL et al. Nanocarriers for tracking and treating diseases. Curr Med Chem, 2013, 20: 3500-3514

[156] Seitz JM, Durisin M, Goldman J et al. Recent advances in biodegradable metals for medical sutures: a critical review. Adv Healthcare Mater, 2015, 4: 1915-1936

[157] Thanganathan U, Nogami M. Investigations on effects of the incorporation of various ionic liquids on PVA based hybrid membranes for proton exchange membrane fuel cells. Int J Hydrogen Energy, 2015, 40: 1935-1944

[158] Ninago MD, López OV, Lencina MS et al. Enhancement of thermoplastic starch final properties by blending with poly (ɛ-caprolactone). Carbohydr Polym, 2015, 134: 205-212

[159] Qi Z, Ye H, Xu J et al. Synthesis and characterizations of attapulgite reinforced branched poly (butylene succinate) nanocomposites. Colloids Surf A, 2013, 436: 26-33

[160] Williams JM, Adewunmi A, Schek RM et al. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials, 2005, 26: 4817-4827

[161] Palamoor M, Jablonski MM. Poly (ortho ester) nanoparticle-based targeted intraocular therapy for controlled release of hydrophilic molecules. Mol Pharm, 2013, 10: 701-708

[162] Gautam S, Dinda AK, Mishra NC. Fabrication and characterization of PCL/gelatin composite nanofibrous scaffold for tissue engineering applications by electrospinning method. Mater Sci Eng C Mater Biol Appl, 2013, 33: 1228-1235

[163] Chopra P, Nayak BG, Handa VG . Development of PVA-carrageenan based scaffolds and evaluating its efficacy on osteosarcoma upon cryopreservation. Thapar University: Patiala, India, 2015.

[164] Major R, Lackner J, Sanak M et al. Silver nanoparticles influence on the blood activation process and their release to blood plasma from synthetic polymer scaffold. IOP Conference Series: Materials Science and Engineering, 2016 IOP Publishing 012031

[165] Ignatius A, Claes LE. in vitro biocompatibility of bioresorbable polymers: poly (L, DL-lactide) and poly (L-lactide-co-glycolide). Biomaterials, 1996, 17: 831-839

[166] Bonzani IC, Adhikari R, Houshyar S et al. Synthesis of two-component injectable polyurethanes for bone tissue engineering. Biomaterials, 2007, 28: 423-433

[167] Wen W, Luo B, Qin X et al. Strengthening and toughening of poly (L-lactide) composites by surface modified MgO whiskers. Appl Surf Sci, 2015, 332: 215-223

[168] Guo Z, Lee SE, Kim H et al. Fabrication, characterization and microwave properties of polyurethane nanocomposites reinforced with iron oxide and barium titanate nanoparticles. Acta Mater, 2009, 57: 267-277

[169] Maitra U, Prasad KE, Ramamurty U et al. Mechanical properties of nanodiamond-reinforced polymer-matrix composites. Solid State Commun, 2009, 149: 1693-1697

[170] Wang G, Zhao M. Influence of polycaprolactone grafted MWNTs on antistatic ability of PVC. Eng Plast Appl, 2010, 38: 10-14

[171] Khan U, May P, O'Neill A et al. Polymer reinforcement using liquid-exfoliated boron nitride nanosheets. Nanoscale, 2013, 5: 581-587

[172] Choi WY, Kim HE, Kim MJ et al. Production and characterization of calcium phosphate (CaP) whisker-reinforced poly (ε-caprolactone) composites as bone regenerative. Mater Sci Eng C, 2010, 30: 1280-1284

[173] Meseguer-Olmo L, Vicente-Ortega V, Alcaraz-Baños M et al. In-vivo behavior of Si-hydroxyapatite/polycaprolactone/DMB scaffolds fabricated by 3D printing. J Biomed Mater Res A, 2013, 101: 2038-2048

[174] Kim SS, Park MS, Gwak SJ et al. Accelerated bonelike apatite growth on porous polymer/ceramic composite scaffolds in vitro. Tissue Eng, 2006, 12: 2997-3006

[175] Duan B, Wang M, Zhou WY et al. Three-dimensional nanocomposite scaffolds fabricated via selective laser sintering for bone tissue engineering. Acta Biomater, 2010, 6: 4495-4505

[176] Nie H, Wang C-H. Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. J Control Release, 2007, 120: 111-121

[177] Cui W, Li X, Chen J et al. In situ growth kinetics of hydroxyapatite on electrospun poly (DL-lactide) fibers with gelatin grafted. Cryst Growth Des, 2008, 8: 4576-4582

[178] Murphy C, Kolan K, Li W. 3D bioprinting of stem cells and polymer/bioactive glass composite scaffolds for bone tissue engineering. Int J Bioprint, 2017, 3: 1-11

[179] Poh PS, Hutmacher DW, Stevens MM et al. Fabrication and in vitro characterization of bioactive glass composite scaffolds for bone regeneration. Biofabrication, 2013, 5: 045005

[180] Wu F, Wei J, Liu C et al. Fabrication and properties of porous scaffold of zein/PCL biocomposite for bone tissue engineering. Composites Part B, 2012, 43: 2192-2197

[181] Bhardwaj N, Kundu SC. Silk fibroin protein and chitosan polyelectrolyte complex porous scaffolds for tissue engineering applications. Carbohydr Polym, 2011, 85: 325-333

[182] Wen W, Zou Z, Luo B et al. in vitro degradation and cytocompatibility of g-MgO whiskers/PLLA composites. J Mater Sci, 2017, 52: 2329-2344

[183] Westhauser F, Weis C, Prokscha M et al. Three-dimensional polymer coated 45S5-type bioactive glass scaffolds seeded with human mesenchymal stem cells show bone formation in vivo. J Mater Sci Mater Med, 2016, 27: 119

[184] Saravanan S, Nethala S, Pattnaik S et al. Preparation, characterization and antimicrobial activity of a bio-composite scaffold containing chitosan/nano-hydroxyapatite/nano-silver for bone tissue engineering. Int J Biol Macromol, 2011, 49: 188-193

[185] Hou JY, Zhang SQ, Ke L. The application of metal materials in exercise-induced bone injury. Adv Mater Res, 2013, 675: 205-208

[186] Bakhsheshi-Rad HR, Hamzah E, Ismail AF et al. Synthesis and corrosion behavior of a hybrid bioceramic-biopolymer coating on biodegradable Mg alloy for orthopaedic implants. J Alloys Compd, 2015, 648: 1067-1071

[187] Draxler J, Martinelli E, Weinberg AM et al. The potential of isotopically enriched Magnesium to study bone implant degradation in vivo. Acta Biomater, 2017, 51: 526-536

[188] Shuai C, Yang Y, Wu P et al. Laser rapid solidification improves corrosion behavior of Mg-Zn-Zr alloy. J Alloys Compd, 2016, 691: 961-969

[189] Yang Y, Wu P, Lin X et al. System development, formability quality and microstructure evolution of selective laser-melted magnesium. Virtual Phys Prototyping, 2016, 11: 173-181

[190] Maurya R, Siddiqui AR, Balani K. in vitro degradation and biomineralization ability of hydroxyapatite coated Mg-9Li-7Al-1Sn and Mg-9Li-5Al-3Sn-1Zn alloys. Surf Coat Technol, 2017, 325: 65-74

[191] Haghshenas M. Mechanical characteristics of biodegradable Qmagnesium matrix composites: a review. J Magnes Alloys, 2017, 5: 189-201

[192] Nile SH, Park SW. Edible berries: bioactive components and their effect on human health. Nutrition, 2014, 30: 134-144

[193] Seitz JM, Eifler R, Bach FW et al. Magnesium degradation products: effects on tissue and human metabolism. J Biomed Mater Res A, 2014, 102: 3744-3753

[194] Atrens A, Narayanan TSNS, Park I-S, Lee M-H. Revolutionising biodegradable biomaterials—significance of magnesium and its alloys. Surface Modification of Magnesium and its Alloys for Biomedical Applications: Biological Interactions, Mechanical Properties and Testing vol. 1, 2015 San Cambridge Woodhead Publishing 3-28

[195] Jin W, Wang G, Lin Z et al. Corrosion resistance and cytocompatibility of tantalum-surface-functionalized biomedical ZK60 Mg alloy. Corros Sci, 2017, 114: 45-56

[196] Orlov D, Ralston KD, Birbilis N et al. Enhanced corrosion resistance of Mg alloy ZK60 after processing by integrated extrusion and equal channel angular pressing. Acta Mater, 2011, 59: 6176-6186

[197] Yang Y, Wu P, Wang Q et al. The enhancement of Mg corrosion resistance by alloying Mn and laser-melting. Materials, 2016, 9: 216

[198] Gu XN, Li N, Zheng YF et al. in vitro study on equal channel angular pressing AZ31 magnesium alloy with and without back pressure. Mater Sci Eng B, 2011, 176: 1802-1806

[199] Cifuentes SC, Benavente R, Lieblich M et al. Biodegradable and bioabsorbable materials for osteosynthesis applications: state-of-the-art and future perspectives. Thakur VK, Thakur MK, Kessler MR (eds). Handbook of Composites from Renewable Materials, Biodegradable Materials vol. 5. John Wiley & Sons: Hoboken, USA 2017, pp 109–144.

[200] Sridhar TM, Vinodhini SP, Mudali UK et al. Load-bearing metallic implants: electrochemical characterisation of corrosion phenomena. Mater Technol, 2016, 31: 705-718

[201] Zeng RC, Jin Z, Huang WJ et al. Review of studies on corrosion of magnesium alloys. Trans Nonferrous Met Soc China, 2006, 16: 763-771

[202] Valente T. Grain boundary effects on the behavior of WE43 magnesium castings in simulated marine environment. J Mater Sci Lett, 2001, 20: 67-69

[203] Lin DJ, Hung FY, Lui TS et al. Heat treatment mechanism and biodegradable characteristics of ZAX1330 Mg alloy. Mater Sci Eng C Mater Biol Appl, 2015, 51: 300-308

[204] Chen K, Dai J, Zhang X. Improvement of corrosion resistance of magnesium alloys for biomedical applications. Corros Rev, 2015, 33: 101-117

[205] Takei R, Umeda J, Kondoh K. Evaluation of galvanic corrosion phenomenon between α-Mg matrix and metallic dispersoids in Mg alloys using surface potential difference. Trans Jpn Soc Mech Eng, 2011, 77: 301-315

[206] Coy AE, Viejo F, Skeldon P et al. Susceptibility of rare-earth-magnesium alloys to micro-galvanic corrosion. Corros Sci, 2010, 52: 3896-3906

[207] Li J, Jiang Q, Sun H et al. Effect of heat treatment on corrosion behavior of AZ63 magnesium alloy in 3.5 wt.% sodium chloride solution. Corros Sci, 2016, 111: 288-301

[208] Jafari S, Raman SinghRK. In-vitro biodegradation and corrosion-assisted cracking of a coated magnesium alloy in modified-simulated body fluid. Mater Sci Eng C Mater Biol Appl, 2017, 78: 278-287

[209] Cao F, Song GL, Atrens A. Corrosion and passivation of magnesium alloys. Corros Sci, 2016, 111: 835-845

[210] Amin MA, Abd El Rehim SS, El-Lithy AS. Pitting and pitting control of Al in gluconic acid solutions-polarization, chronoamperometry and morphological studies. Corros Sci, 2010, 52: 3099-3108

[211] Huttunen-Saarivirta E, Kuokkala VT, Kokkonen J et al. Corrosion effects of runway de-icing chemicals on aircraft alloys and coatings. Mater Chem Phys, 2011, 126: 138-151

[212] Li J, Cao P, Zhang X et al. in vitro degradation and cell attachment of a PLGA coated biodegradable Mg-6Zn based alloy. J Mater Sci, 2010, 45: 6038-6045

[213] Hofstetter J, Martinelli E, Pogatscher S et al. Influence of trace impurities on the in vitro and in vivo degradation of biodegradable Mg-5Zn-0.3Ca alloys. Acta Biomater, 2015, 23: 347-353

[214] Gusieva K, Davies C, Scully J et al. Corrosion of magnesium alloys: the role of alloying. Int Mater Rev, 2015, 60: 169-194

[215] Zhang HJ, Zhang DF, Ma CH et al. Improving mechanical properties and corrosion resistance of Mg-6Zn-Mn magnesium alloy by rapid solidification. Mater Lett, 2013, 92: 45-48

[216] Prasad A, Uggowitzer PJ, Shi Z et al. Production of high purity magnesium alloys by melt purification with Zr. Adv Eng Mater, 2012, 14: 477-490

[217] Song G. Control of biodegradation of biocompatable magnesium alloys. Corros Sci, 2007, 49: 1696-1701

[218] Qiao Z, Shi Z, Hort N et al. Corrosion behaviour of a nominally high purity Mg ingot produced by permanent mould direct chill casting. Corros Sci, 2012, 61: 185-207

[219] Cao F, Shi Z, Hofstetter J et al. Corrosion of ultra-high-purity Mg in 3.5% NaCl solution saturated with Mg(OH)2. Corros Sci, 2013, 75: 78-99

[220] Peng Q, Huang Y, Le Z et al. Preparation and properties of high purity Mg-Y biomaterials. Biomaterials, 2010, 31: 398-403

[221] Schlüter K, Shi Z, Zamponi C et al. Corrosion performance and mechanical properties of sputter-deposited MgY and MgGd alloys. Corros Sci, 2014, 78: 43-54

[222] Friedrich HE, Mordike BL. Magnesium Technology—Metallurgy, Design Data, Application. Berlin Heidelberg: Springer-Verlag, 2006.

[223] Chen J, Song Y, Shan D et al. Influence of alloying elements and microstructure on the formation of hydrotalcite film on Mg alloys. Corros Sci, 2015, 93: 90-99

[224] Willbold E, Gu X, Albert D et al. Effect of the addition of low rare earth elements (lanthanum, neodymium, cerium) on the biodegradation and biocompatibility of magnesium. Acta Biomater, 2015, 11: 554-562

[225] Velikokhatnyi OI, Kumta PN. First-principles studies on alloying and simplified thermodynamic aqueous chemical stability of calcium-, zinc-, aluminum-, yttrium- and iron-doped magnesium alloys. Acta Biomater, 2009, 6: 1698-1704

[226] Rosalbino F, Angelini E, Negri SD et al. Effect of erbium addition on the corrosion behaviour of Mg-Al alloys. Intermetallics, 2005, 13: 55-60

[227] Bakhsheshi-Rad HR, Idris MH, Abdul-Kadir MR et al. Mechanical and bio-corrosion properties of quaternary Mg-Ca-Mn-Zn alloys compared with binary Mg-Ca alloys. Mater Des, 2014, 53: 283-292

[228] Ben-Hamu G, Eliezer D, Shin KS et al. The relation between microstructure and corrosion behavior of Mg-Y-RE-Zr alloys. J Alloys Compd, 2007, 431: 269-276

[229] Jia R, Zhang M, Zhang L et al. Correlative change of corrosion behavior with the microstructure of AZ91 Mg alloy modified with Y additions. J Alloys Compd, 2015, 634: 263-271

[230] Choi JY, Kim WJ. Significant effects of adding trace amounts of Ti on the microstructure and corrosion properties of Mg-6Al-1Zn magnesium alloy. J Alloys Compd, 2014, 614: 49-55

[231] Zhou X, Huang Y, Wei Z et al. Improvement of corrosion resistance of AZ91D magnesium alloy by holmium addition. Corros Sci, 2006, 48: 4223-4233

[232] Zhao MC, Liu M, Song G et al. Influence of the β-phase morphology on the corrosion of the Mg alloy AZ91. Corros Sci, 2008, 50: 1939-1953

[233] Zhang XB, He XC, Xue YJ et al. Effects of Sr on microstructure and corrosion resistance in simulated body fluid of as cast Mg-Nd-Zr magnesium alloys. Corros Eng Sci Technol, 2014, 49: 345-351

[234] Li X, Liu X, Wu S et al. Design of magnesium alloys with controllable degradation for biomedical implants: from bulk to surface. Acta Biomater, 2016, 45: 2-30

[235] Hagihara K, Okubo M, Yamasaki M et al. Crystal-orientation-dependent corrosion behaviour of single crystals of a pure Mg and Mg-Al and Mg-Cu solid solutions. Corros Sci, 2016, 109: 68-85

[236] Samaniego A, Gusieva K, Llorente I et al. Exploring the possibility of protective surface oxides upon Mg alloy AZ31 via lutetium additions. Corros Sci, 2014, 89: 101-110

[237] Birbilis N, Williams G, Gusieva K et al. Poisoning the corrosion of magnesium. Electrochem Commun, 2013, 34: 295-298

[238] Hornberger H, Virtanen S, Boccaccini AR. Biomedical coatings on magnesium alloys-a review. Acta Biomater, 2012, 8: 2442-2455

[239] Wagener V, Killian MS, Turhan CM et al. Albumin coating on magnesium via linker molecules-comparing different coating mechanisms. Colloids Surf B Biointerfaces, 2013, 103: 586-594

[240] Wong HM, Yeung KW, Lam KO et al. A biodegradable polymer-based coating to control the performance of magnesium alloy orthopaedic implants. Biomaterials, 2010, 31: 2084-2096

[241] Shen S, Cai S, Xu G et al. Influence of heat treatment on bond strength and corrosion resistance of sol-gel derived bioglass-ceramic coatings on magnesium alloy. J Mech Behav Biomed, 2015, 45: 166-174

[242] Zeng RC, Zhang F, Lan ZD et al. Corrosion resistance of calcium-modified zinc phosphate conversion coatings on magnesium-aluminium alloys. Corros Sci, 2014, 88: 452-459

[243] Zhao Q, Guo X, Dang X et al. Preparation and properties of composite MAO/ECD coatings on magnesium alloy. Colloids Surf B Biointerfaces, 2013, 102: 321-326

[244] Yazdimamaghani M, Razavi M, Vashaee D et al. Surface modification of biodegradable porous Mg bone scaffold using polycaprolactone/bioactive glass composite. Mater Sci Eng C Mater Biol Appl, 2015, 49: 436-444

[245] Hahn Byung-Dong Park et al Aerosol deposition of hydroxyapatite-chitosan composite coatings on biodegradable magnesium alloy. Surf Coat Technol, 2011, 205: 3112-3118

[246] Razavi M, Fathi M, Savabi O et al. Controlling the degradation rate of bioactive magnesium implants by electrophoretic deposition of akermanite coating. Ceram Int, 2014, 40: 3865-3872

[247] Razavi M, Fathi M, Savabi O et al. Coating of biodegradable magnesium alloy bone implants using nanostructured diopside (CaMgSi2O6). Appl Surf Sci, 2014, 288: 130-137

[248] Hiromoto S. Self-healing property of hydroxyapatite and octacalcium phosphate coatings on pure magnesium and magnesium alloy. Corros Sci, 2015, 100: 284-294

[249] Gao JH, Guan SK, Chen J et al. Fabrication and characterization of rod-like nano-hydroxyapatite on MAO coating supported on Mg-Zn-Ca alloy. Appl Surf Sci, 2011, 257: 2231-2237

[250] Willbold E, Kalla K, Bartsch I et al. Biocompatibility of rapidly solidified magnesium alloy RS66 as a temporary biodegradable metal. Acta Biomater, 2013, 9: 8509-8517

[251] Guan YC, Zhou W, Li ZL et al. Study on the solidification microstructure in AZ91D Mg alloy after laser surface melting. Appl Surf Sci, 2009, 255: 8235-8238

[252] Zhao C, Pan F, Zhao S et al. Microstructure, corrosion behavior and cytotoxicity of biodegradable Mg-Sn implant alloys prepared by sub-rapid solidification. Mater Sci Eng C Mater Biol Appl, 2015, 54: 245-251

[253] Hehmann F, Sommer F, Predel B. Extension of solid solubility in magnesium by rapid solidification. Mater Sci Eng A, 1990, 125: 249-265

[254] Aghion E, Jan L, Meshi L et al. Increased corrosion resistance of the AZ80 magnesium alloy by rapid solidification. J Biomed Mater Res B Appl Biomater, 2015, 103: 1541-1548

[255] Hakimi O, Aghion E, Goldman J. Improved stress corrosion cracking resistance of a novel biodegradable EW62 magnesium alloy by rapid solidification, in simulated electrolytes. Mater Sci Eng C Mater Biol Appl, 2015, 51: 226-232

[256] Nooeaid P, Salih V, Beier JP et al. Osteochondral tissue engineering: scaffolds, stem cells and applications. J Cell Mol Med, 2012, 16: 2247-2270

[257] Wu Y, Gao G, Wu G. Self-assembled three-dimensional hierarchical porous V2O5/graphene hybrid aerogels for supercapacitors with high energy density and long cycle life. J Mater Chem A, 2015, 3: 1828-1832

[258] Liu C, Miller H, Sharma S et al. Analyzing actin dynamics during the activation of the B cell receptor in live B cells. Biochem Biophys Res Commun, 2012, 427: 202-206

[259] Wolfenson H, Lavelin I, Geiger B. Dynamic Regulation of the Structure and Functions of Integrin Adhesions. Dev Cell, 2013, 24: 447-458

[260] Gao C, Deng Y, Feng P et al. Current progress in bioactive ceramic scaffolds for bone repair and regeneration. Int J Mol Sci, 2014, 15: 4714-4732

[261] Naleway SE, Porter MM, McKittrick J et al. Structural design elements in biological materials: application to bioinspiration. Adv Mater, 2015, 27: 5455-5476

[262] Wang X, Xu S, Zhou S et al. Topological design and additive manufacturing of porous metals for bone scaffolds and orthopaedic implants: a review. Biomaterials, 2016, 83: 127-141

[263] Qi YM, Yang LJ, Wang LL. Finite-element analysis and optimization for gradient porous structure of artificial bone. Appl Mech Mater, 2012, 271-272: 922-926

[264] Qiu LL, Choong C. Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng Part B Rev, 2013, 19: 485-502

[265] Derby B. Printing and prototyping of tissues and scaffolds. Science, 2012, 338: 921-926

[266] Lee M, Wu BM . Recent advances in 3D printing of tissue engineering scaffolds. Comput Aided Tissue Eng 2012, 257–267.

[267] Sultana N, Wang M. PHBV/PLLA-based composite scaffolds fabricated using an emulsion freezing/freeze-drying technique for bone tissue engineering: surface modification and in vitro biological evaluation. Biofabrication, 2012, 4: 015003

[268] Yang J, Cai H, Lv J et al. in vivo study of a self-stabilizing artificial vertebral body fabricated by electron beam melting. Spine, 2014, 39: 486-492

[269] Won JE, Mateos-Timoneda MA, Castano O et al. Fibronectin immobilization on to robotic-dispensed nanobioactive glass/polycaprolactone scaffolds for bone tissue engineering. Biotechnol Lett, 2015, 37: 935-942

[270] Hunger PM, Donius AE, Wegst UG. Structure-property-processing correlations in freeze-cast composite scaffolds. Acta Biomater, 2013, 9: 6338-6348

[271] Desimone D, Li W, Roether JA et al. Biosilicate®-gelatine bone scaffolds by the foam replica technique: development and characterization. Sci Technol Adv Mat, 2013, 14: 045008

[272] Tayton E, Purcell M, Aarvold A et al. Supercritical CO2 fluid-foaming of polymers to increase porosity: A method to improve the mechanical and biocompatibility characteristics for use as a potential alternative to allografts in impaction bone grafting? Acta Biomater, 2012, 8: 1918-1927

[273] Ji C, Annabi N, Khademhosseini A et al. Fabrication of porous chitosan scaffolds for soft tissue engineering using dense gas CO2. Acta Biomater, 2011, 7: 1653-1664

[274] Tadic D, Beckmann F, Schwarz K et al. A novel method to produce hydroxyapatite objects with interconnecting porosity that avoids sintering. Biomaterials, 2004, 25: 3335-3340

[275] Nazemi K, Moztarzadeh F, Jalali N et al. Synthesis and characterization of poly (lactic-co-glycolic) acid nanoparticles-loaded chitosan/bioactive glass scaffolds as a localized delivery system in the bone defects. Biomed Res Int, 2014, 2014: 898930

[276] Tığlı RS, Karakeçili A, Gümüşderelioğlu M. in vitro characterization of chitosan scaffolds: influence of composition and deacetylation degree. J Mater Sci Mater Med, 2007, 18: 1665-1674

[277] Guan J, Fujimoto KL, Sacks MS et al. Preparation and characterization of highly porous, biodegradable polyurethane scaffolds for soft tissue applications. Biomaterials, 2005, 26: 3961-3971

[278] Nejati E, Mirzadeh H, Zandi M. Synthesis and characterization of nano-hydroxyapatite rods/poly (l-lactide acid) composite scaffolds for bone tissue engineering. Composites Part A, 2008, 39: 1589-1596

[279] Lou T, Wang X, Song G et al. Fabrication of PLLA/β-TCP nanocomposite scaffolds with hierarchical porosity for bone tissue engineering. Int J Biol Macromol, 2014, 69: 464-470

[280] Mikos AG, Sarakinos G, Leite SM et al. Laminated three-dimensional biodegradable foams for use in tissue engineering. Biomaterials, 1993, 14: 323-330

[281] Meng Z, Wang Y, Ma C et al. Electrospinning of PLGA/gelatin randomly-oriented and aligned nanofibers as potential scaffold in tissue engineering. Mater Sci Eng C, 2010, 30: 1204-1210

[282] Tripathi G, Basu B. A porous hydroxyapatite scaffold for bone tissue engineering: physico-mechanical and biological evaluations. Ceram Int, 2012, 38: 341-349

[283] Kaufmann EE, Ducheyne P, Shapiro I. Evaluation of osteoblast response to porous bioactive glass (45S5) substrates by RT-PCR analysis. Tissue Eng, 2000, 6: 19-28

[284] Ma J, Wang C, Peng KW. Electrophoretic deposition of porous hydroxyapatite scaffold. Biomaterials, 2003, 24: 3505-3510

[285] Shin M, Yoshimoto H, Vacanti JP. in vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun nanofibrous scaffold. Tissue Eng, 2004, 10: 33-41

[286] Oh SH, Park IK, Kim JM et al. In vitro and in vivo characteristics of PCL scaffolds with pore size gradient fabricated by a centrifugation method. Biomaterials, 2007, 28: 1664-1671

[287] Hoque ME, Chuan YL, Pashby I. Extrusion based rapid prototyping technique: an advanced platform for tissue engineering scaffold fabrication. Biopolymers, 2012, 97: 83-93

[288] Campbell I, Bourell D, Gibson I. Additive manufacturing: rapid prototyping comes of age. Rapid Prototyping J, 2012, 18: 255-258

[289] Liao Y, Song J, Li E et al. Rapid prototyping of three-dimensional microfluidic mixers in glass by femtosecond laser direct writing. Lab on A Chip, 2012, 12: 746-749

[290] Billiet T, Vandenhaute M, Schelfhout J et al. A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials, 2012, 33: 6020-6041

[291] Eshraghi S, Das S. Micromechanical finite-element modeling and experimental characterization of the compressive mechanical properties of polycaprolactone-hydroxyapatite composite scaffolds prepared by selective laser sintering for bone tissue engineering. Acta Biomater, 2012, 8: 3138-3143

[292] Liao H, Lee M, Tsai W et al. Osteogenesis of adipose-derived stem cells on polycaprolactone-β-tricalcium phosphate scaffold fabricated via selective laser sintering and surface coating with collagen type I. J Tissue Eng Regen Med, 2016, 10: E337-E353

[293] Gauvin R, Chen YC, Lee JW et al. Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography. Biomaterials, 2012, 33: 3824-3834

[294] Elomaa L, Teixeira S, Hakala R et al. Preparation of poly(ε-caprolactone)-based tissue engineering scaffolds by stereolithography. Acta Biomater, 2011, 7: 3850-3856

[295] Korpela J, Kokkari A, Korhonen H et al. Biodegradable and bioactive porous scaffold structures prepared using fused deposition modeling. J Biomed Mater Res B Appl Biomater, 2013, 101: 610-619

[296] Duan B, Wang M, Schmidt V, Belegratis MR. Selective laser sintering and its biomedical applications. Laser Technology in Biomimetics: Basics and Applications, 2013 Berlin Heidelberg Springer Berlin Heidelberg 83-109

[297] Kim K, Dean D, Wallace J et al. The influence of stereolithographic scaffold architecture and composition on osteogenic signal expression with rat bone marrow stromal cells. Biomaterials, 2011, 32: 3750-3763

[298] Zein I, Hutmacher DW, Tan KC et al. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials, 2002, 23: 1169-1185

[299] Banerjee SS, Tarafder S, Davies NM et al. Understanding the influence of MgO and SrO binary doping on the mechanical and biological properties of beta-TCP ceramics. Acta Biomater, 2010, 6: 4167-4174

[300] Salmoria GV, Klauss P, Zepon K et al. Development of functionally-graded reservoir of PCL/PG by selective laser sintering for drug delivery devices. Virtual Phys Prototyping, 2012, 7: 107-115

[301] Kang MH, Jang TS, Kim SW et al. MgF2-coated porous magnesium/alumina scaffolds with improved strength, corrosion resistance, and biological performance for biomedical applications. Mater Sci Eng C Mater Biol Appl, 2016, 62: 634-642

[302] Wei J, Jia J, Wu F et al. Hierarchically microporous/macroporous scaffold of magnesium-calcium phosphate for bone tissue regeneration. Biomaterials, 2010, 31: 1260-1269

[303] Katarivas LG, Ventura Y, Goldman J et al. Cytotoxic characteristics of biodegradable EW10X04 Mg alloy after Nd coating and subsequent heat treatment. Mater Sci Eng C Mater Biol Appl, 2016, 62: 752-761

[304] Tan L, Gong M, Zheng F et al. Study on compression behavior of porous magnesium used as bone tissue engineering scaffolds. Biomed Mater, 2009, 4: 015016

[305] Liu YJ, Yang ZY, Tan LL et al. An animal experimental study of porous magnesium scaffold degradation and osteogenesis. Braz J Med Biol Res, 2014, 47: 715-720

[306] Chen Z, Mao X, Tan L et al. Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate. Biomaterials, 2014, 35: 8553-8565

[307] Yu W, Zhao H, Ding Z et al. in vitro and in vivo evaluation of MgF2 coated AZ31 magnesium alloy porous scaffolds for bone regeneration. Colloids Surf B Biointerfaces, 2017, 149: 330-340

[308] Nguyen TL, Staiger MP, Dias GJ et al. A novel manufacturing route for fabrication of topologically-ordered porous magnesium scaffolds. Adv Eng Mater, 2011, 13: 872-881

[309] Suntornnond R, An J, Tijore A et al. A solvent-free surface suspension melt technique for making biodegradable PCL membrane scaffolds for tissue engineering applications. Molecules, 2016, 21: 386

[310] Lee B, Lee T, Lee Y et al. Space-holder effect on designing pore structure and determining mechanical properties in porous titanium. Mater Des, 2014, 57: 712-718

[311] Osorio-Hernández JO, Suarez MA, Goodall R et al. Manufacturing of open-cell Mg foams by replication process and mechanical properties. Mater Des, 2014, 64: 136-141

[312] Tiyyagura HR, Rudolf R, Gorgieva S et al. The chitosan coating and processing effect on the physiological corrosion behaviour of porous magnesium monoliths. Prog Org Coat, 2016, 99: 147-156

[313] Seyedraoufi ZS, Mirdamadi S. Effects of pulse electrodeposition parameters and alkali treatment on the properties of nano hydroxyapatite coating on porous Mg-Zn scaffold for bone tissue engineering application. Mater Chem Phys, 2014, 148: 519-527

[314] Jiang G, Li Q, Wang C et al. Characterization and investigation of the deformation behavior of porous magnesium scaffolds with entangled architectured pore channels. J Mech Behav Biomed, 2016, 64: 139-150

[315] Cheng MQ, Wahafu T, Jiang GF et al. A novel open-porous magnesium scaffold with controllable microstructures and properties for bone regeneration. Sci Rep, 2016, 6: 24134

[316] Kirkland NT, Kolbeinsson I, Woodfield T et al. Synthesis and properties of topologically ordered porous magnesium. Mater Sci Eng B, 2011, 176: 1666-1672

[317] Saad APM, Jasmawati N, Harun MN et al. Dynamic degradation of porous magnesium under a simulated environment of human cancellous bone. Corros Sci, 2016, 112: 495-506

[318] Zhang X, Li XW, Li JG et al. Preparation and mechanical property of a novel 3D porous magnesium scaffold for bone tissue engineering. Mater Sci Eng C Mater Biol Appl, 2014, 42: 362-367

[319] Marques AC, Almeida RM, Thiema A et al. Sol-gel-derived glass scaffold with high pore interconnectivity and enhanced bioactivity. J Mater Res, 2009, 24: 3495-3502

[320] Cox SC. Synthesis and 3D printing of hydroxyapatite scaffolds for applications in bone tissue engineering, 2013 Coventry, UK University of Warwick

[321] Liu FH, Shen YK, Lee JL. Selective laser sintering of a hydroxyapatite-silica scaffold on cultured MG63 osteoblasts in vitro. Int J Precis Eng Manuf, 2012, 13: 439-444

[322] Zhu W, Wang M, Fu Y et al. Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study. Acta Biomater, 2014, 14: 164-174

[323] Jelen C, Mattei G, Montemurro F et al. Bone scaffolds with homogeneous and discrete gradient mechanical properties. Mater Sci Eng C Mater Biol Appl, 2013, 33: 28-36

[324] Du Y, Liu H, Shuang J et al. Microsphere-based selective laser sintering for building macroporous bone scaffolds with controlled microstructure and excellent biocompatibility. Colloids Surf B Biointerfaces, 2015, 135: 81-89

[325] Nedjari S, Schlatter G, Hébraud A. Thick electrospun honeycomb scaffolds with controlled pore size. Mater Lett, 2015, 142: 180-183

[326] Tian B, Liu J, Dvir T et al. Macroporous nanowire nanoelectronic scaffolds for synthetic tissues. Nat Mater, 2012, 11: 986-994

[327] Ambre AH, Katti DR, Katti KS. Nanoclays mediate stem cell differentiation and mineralized ECM formation on biopolymer scaffolds. J Biomed Mater Res A, 2013, 101: 2644-2660

[328] Yang F, Murugan R, Ramakrishna S et al. Fabrication of nano-structured porous PLLA scaffold intended for nerve tissue engineering. Biomaterials, 2004, 25: 1891-1900

[329] Kim HH, Park YH, Yoon KJ et al. Fabrication of nanofibrous silkworm gland three-dimensional scaffold containing micro/nanoscale pores and study of its effects on adipose tissue-derived stem cell growth. J Mater Sci, 2016, 51: 9267-9278

[330] Xia L, Lin K, Jiang X et al. Effect of nano-structured bioceramic surface on osteogenic differentiation of adipose derived stem cells. Biomaterials, 2014, 35: 8514-8527

[331] Seunarine K, Meredith DO, Riehle MO et al. Biodegradable polymer tubes with lithographically controlled 3D micro- and nanotopography. Microelectron Eng, 2008, 85: 1350-1354

[332] Pattison MA, Wurster S, Webster TJ et al. Three-dimensional, nano-structured PLGA scaffolds for bladder tissue replacement applications. Biomaterials, 2005, 26: 2491-2500

[333] Kang MS, Kim JH, Singh RK et al. Therapeutic-designed electrospun bone scaffolds: mesoporous bioactive nanocarriers in hollow fiber composites to sequentially deliver dual growth factors. Acta Biomater, 2015, 16: 103-116

[334] Ma MS, Kannan V, de Vries AE et al. Characterization and comparison of osteoblasts derived from mouse embryonic stem cells and induced pluripotent stem cells. J Bone Miner Metab, 2017, 35: 21-30

[335] Kang Y, Georgiou AI, MacFarlane RJ et al. Fibronectin stimulates the osteogenic differentiation of murine embryonic stem cells. J Tissue Eng Regen Med, 2015, 11: 1929-1940

[336] Rao V, Shih YRV, Kang H et al. Adenosine signaling mediates osteogenic differentiation of human embryonic stem cells on mineralized matrices. Front Bioeng Biotechnol, 2015, 3: 185

[337] Ehnes D, Geransar R, Rancourt D et al. Exogenous nitric oxide enhances calcification in embryonic stem cell-derived osteogenic cultures. Differentiation, 2015, 89: 97-103

[338] Zou L, Kidwai FK, Kopher RA et al. Use of RUNX2 expression to identify osteogenic progenitor cells derived from human embryonic stem cells. Stem Cell Rep, 2015, 4: 190-198

[339] Yu Y, Al-Mansoori L, Opas M. Optimized osteogenic differentiation protocol from R1 mouse embryonic stem cells in vitro. Differentiation, 2015, 89: 1-10

[340] Tang M, Chen W, Weir MD et al. Human embryonic stem cell encapsulation in alginate microbeads in macroporous calcium phosphate cement for bone tissue engineering. Acta Biomater, 2012, 8: 3436-3445

[341] Rutledge K, Cheng Q, Pryzhkova M et al. Enhanced differentiation of human embryonic stem cells on extracellular matrix-containing osteomimetic scaffolds for bone tissue engineering. Tissue Eng Part C, 2014, 20: 865-874

[342] Korkusuz P, Kose S, Zubeyde Kopru C. Biomaterial and stem cell interactions: histological biocompatibility. Curr Stem Cell Res Ther, 2016, 11: 475-486

[343] Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284: 143-147

[344] Xiao Y, Mareddy S, Crawford R. Clonal characterization of bone marrow derived stem cells and their application for bone regeneration. Int J Oral Sci, 2010, 2: 127-135

[345] Marmotti A, de Girolamo L, Bonasia DE et al. Bone marrow derived stem cells in joint and bone diseases: a concise review. Int Orthop, 2014, 38: 1787-1801

[346] Berglund IS, Dirr EW, Ramaswamy V et al. The effect of Mg-Ca-Sr alloy degradation products on human mesenchymal stem cells. J Biomed Mater Res B Appl Biomater 2017, doi: 10.1002/jbm.b.33869 [Epub ahead of print].

[347] Yu WL, Sun TW, Qi C et al. Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration. Sci Rep, 2017, 7: 44129

[348] Marei NH, El-Sherbiny IM, Lotfy A et al. Mesenchymal stem cells growth and proliferation enhancement using PLA vs PCL based nanofibrous scaffolds. Int J Biol Macromol, 2016, 93: 9-19

[349] Watson N, Divers R, Kedar R et al. Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells. Cytotherapy, 2015, 17: 18-24

[350] Penny J, Harris P, Shakesheff K et al. The biology of equine mesenchymal stem cells: phenotypic characterization, cell surface markers and multilineage differentiation. Front Biosci, 2012, 17: 892-908

[351] Wang F, Zhang YC, Zhou H et al. Evaluation of in vitro and in vivo osteogenic differentiation of nano-hydroxyapatite/chitosan/poly (lactide-co-glycolide) scaffolds with human umbilical cord mesenchymal stem cells. J Biomed Mater Res A, 2014, 102: 760-768

[352] Guan F, Ma S, Shi X et al. Biocompatibility of nano-hydroxyapatite/Mg-Zn-Ca alloy composite scaffolds to human umbilical cord mesenchymal stem cells from Wharton's jelly in vitro. Sci China Life Sci, 2014, 57: 181-187

[353] Wang F, Su XX, Guo YC et al. Bone regeneration by nanohydroxyapatite/chitosan/poly (lactide-co-glycolide) scaffolds seeded with human umbilical cord mesenchymal stem cells in the calvarial defects of the nude mice. Biomed Res Int, 2015, 2015: 261938

[354] Gronthos S, Mankani M, Brahim J et al. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci, 2000, 97: 13625-13630

[355] Gronthos S, Brahim J, Li W et al. Stem cell properties of human dental pulp stem cells. J Dent Res, 2002, 81: 531-535

[356] Ledesma-Martínez E, Mendoza-Núñez VM, Santiago-Osorio E, Mesenchymal Stem Cells. Derived from dental pulp: a review. Stem Cells Int, 2015, 2016: 4709572

[357] Seong JM, Kim BC, Park JH et al. Stem cells in bone tissue engineering. Biomed Mater, 2010, 5: 062001

[358] Khanna-Jain R, Mannerström B, Vuorinen A et al. Osteogenic differentiation of human dental pulp stem cells on β-tricalcium phosphate/poly (l-lactic acid/caprolactone) three-dimensional scaffolds. J Tissue Eng, 2012, 3: 2041731412467998

[359] Widbiller M, Lindner SR, Buchalla W et al. Three-dimensional culture of dental pulp stem cells in direct contact to tricalcium silicate cements. Clin Oral Investig, 2016, 20: 237-246

[360] Jensen J, Kraft DCE, Lysdahl H et al. Functionalization of polycaprolactone scaffolds with hyaluronic acid and β-TCP facilitates migration and osteogenic differentiation of human dental pulp stem cells in vitro. Tissue Eng Part A, 2014, 21: 729-739

[361] Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126: 663-676

[362] Lou X. Induced pluripotent stem cells as a new strategy for osteogenesis and bone regeneration. Stem Cell Rev Rep, 2015, 11: 645-651

[363] Holzwarth JM, Ma PX. Biomimetic nanofibrous scaffolds for bone tissue engineering. Biomaterials, 2011, 32: 9622-9629

[364] D’Angelo F, Armentano I, Cacciotti I et al. Tuning multi/pluri-potent stem cell fate by electrospun poly (L-lactic acid)-calcium-deficient hydroxyapatite nanocomposite mats. Biomacromolecules, 2012, 13: 1350-1360

[365] Cho YD, Bae HS, Lee DS et al. Epigenetic priming confers direct cell trans-differentiation from adipocyte to osteoblast in a transgene-free state. J Cell Physiol, 2016, 231: 1484-1494

[366] Tansriratanawong K, Tamaki Y, Ishikawa H et al. Co-culture with periodontal ligament stem cells enhances osteogenic gene expression in de-differentiated fat cells. Hum Cell, 2014, 27: 151-161

[367] Cho YD, Yoon WJ, Kim WJ et al. Epigenetic modifications and canonical wingless/int-1 class (WNT) signaling enable trans-differentiation of nonosteogenic cells into osteoblasts. J Biol Chem, 2014, 289: 20120-20128

[368] Sun Y, Chen CS, Fu J. Forcing stem cells to behave: a biophysical perspective of the cellular microenvironment. Annu Rev Biophys, 2012, 41: 519-542

[369] Zhukova Yulia, Hiepen Christian, Knaus Petra, Osterland Marc, Prohaska Steffen, Dunlop John W. C., Fratzl Peter, Skorb Ekaterina V.. The Role of Titanium Surface Nanostructuring on Preosteoblast Morphology, Adhesion, and Migration. Advanced Healthcare Materials, 2017, 6 15 1601244

[370] Aiyelabegan HT, Sadroddiny E. Fundamentals of protein and cell interactions in biomaterials. Biomed Pharmacother, 2017, 88: 956-970

[371] McMurray RJ, Dalby MJ, Tsimbouri PM. Using biomaterials to study stem cell mechanotransduction, growth and differentiation. J Tissue Eng Regen Med, 2015, 9: 528-539

[372] Chiu LH, Lai WF, Chang SF et al. The effect of type II collagen on MSC osteogenic differentiation and bone defect repair. Biomaterials, 2014, 35: 2680-2691

[373] Hozumi K, Fujimori C, Katagiri F et al. Suppression of cell adhesion through specific integrin crosstalk on mixed peptide-polysaccharide matrices. Biomaterials, 2015, 37: 73-81

[374] Shie MY, Ding SJ. Integrin binding and MAPK signal pathways in primary cell responses to surface chemistry of calcium silicate cements. Biomaterials, 2013, 34: 6589-6606

[375] Biggs MJ, Richards RG, Gadegaard N et al. The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+ enriched skeletal stem cells. Biomaterials, 2009, 30: 5094-5103

[376] Xu W, Liu B, Liu X et al. Regulation of BMP2-induced intracellular calcium increases in osteoblasts. J Orth Res, 2016, 34: 1725-1733

[377] Gallinetti S, Mestres G, Canal C et al. A novel strategy to enhance interfacial adhesion in fiber-reinforced calcium phosphate cement. J Mech Behav Biomed, 2017, 75: 495-503

[378] Bubik S, Payer M, Arnetzl G et al. Attachment and growth of human osteoblasts on different biomaterial surfaces. Int J Comput Dent, 2017, 20: 229-243

[379] Perikamana S, Shin YM, Lee JK et al. Graded functionalization of biomaterial surfaces using mussel-inspired adhesive coating of polydopamine. Colloids Surf B Biointerfaces, 2017, 159: 546-556

[380] Zhou Q, Castañeda OO, Guimarães C et al. Screening platform for cell contact guidance based on inorganic biomaterial micro/nanotopographical gradients. ACS Appl Mater Interfaces, 2017, 9: 31433-31445

[381] Coelho NM, Llopis-Hernández V, Salmerón-Sánchez M et al. Chapter four—dynamic reorganization and enzymatic remodeling of type IV collagen at cell-biomaterial interface. Adv Protein Chem Struct Biol, 2016, 105: 81-104

[382] Ledda M, De BA, Bertani FR et al. Interdisciplinary approach to cell-biomaterial interactions: biocompatibility and cell friendly characteristics of RKKP glass-ceramic coatings on titanium. Biomed Mater, 2015, 10: 035005

[383] Kakinoki S, Yamaoka T. Single-step immobilization of cell adhesive peptides on a variety of biomaterial substrates via tyrosine oxidation with copper catalyst and hydrogen peroxide. Bioconj Chem, 2015, 26: 639-644

[384] Kim SE, Jia W, Jordan AM et al. Surface modification of melt extruded poly(ε-caprolactone) nanofibers: toward a new scalable biomaterial scaffold. ACS Macro Letters, 2014, 3: 585-589

[385] Gemini-Piperni S, Milani R, Bertazzo S et al. Kinome profiling of osteoblasts on hydroxyapatite opens new avenues on biomaterial cell signaling. Biotechnol Bioeng, 2014, 111: 1900-1905

[386] Doyle AD, Yamada KM. Mechanosensing via cell-matrix adhesions in 3D microenvironments. Exp Cell Res, 2016, 343: 60-66

[387] Termini CM, Cotter ML, Marjon KD et al. The membrane scaffold CD82 regulates cell adhesion by altering α4 integrin stability and molecular density. Mol Biol Cell, 2014, 25: 1560-1573

[388] Iskratsch T, Yu CH, Mathur A et al. FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration. Dev Cell, 2013, 27: 545-559

[389] Shih YR, Hwang Y, Phadke A et al. Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. Proc Natl Acad Sci, 2014, 111: 990-995

[390] Kang H, Shih YR, Nakasaki M et al. Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts. Sci Adv, 2016, 2: e1600691

[391] Pullisaar H, Reseland JE, Haugen HJ et al. Simvastatin coating of TiO2 scaffold induces osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. Biochem Biophys Res Commun, 2014, 447: 139-144

[392] Ren X, Tu V, Bischoff D et al. Nanoparticulate mineralized collagen scaffolds induce in vivo bone regeneration independent of progenitor cell loading or exogenous growth factor stimulation. Biomaterials, 2016, 89: 67-78

[393] Luo Y, Shen H, Fang Y et al. Enhanced proliferation and osteogenic differentiation of mesenchymal stem cells on graphene oxide-incorporated electrospun poly (lactic-co-glycolic acid) nanofibrous mats. ACS Appl Mater Interfaces, 2015, 7: 6331-6339

[394] Li X, Wang X, Jiang X et al. Boron nitride nanotube-enhanced osteogenic differentiation of mesenchymal stem cells. J Biomed Mater Res B Appl Biomater, 2016, 104: 323-329

[395] Shuai C, Gao C, Feng P et al. Boron nitride nanotubes reinforce tricalcium phosphate scaffolds and promote the osteogenic differentiation of mesenchymal stem cells. J Biomed Nanotechnol, 2016, 12: 934-947

[396] Wang J, Liu D, Guo B et al. Role of biphasic calcium phosphate ceramic-mediated secretion of signaling molecules by macrophages in migration and osteoblastic differentiation of MSCs. Acta Biomater, 2017, 51: 447-460

[397] Chen B, Lin T, Yang X et al. Low-magnitude, high-frequency vibration promotes the adhesion and the osteogenic differentiation of bone marrow-derived mesenchymal stem cells cultured on a hydroxyapatite-coated surface: the direct role of Wnt/β-catenin signaling pathway activation. Int J Mol Med, 2016, 38: 1531-1540

[398] Hao L, Fu X, Li T et al. Surface chemistry from wettability and charge for the control of mesenchymal stem cell fate through self-assembled monolayers. Colloids Surf B Biointerfaces, 2016, 148: 549-556

[399] Yan X, Yang W, Shao Z et al. Graphene/single-walled carbon nanotube hybrids promoting osteogenic differentiation of mesenchymal stem cells by activating p38 signaling pathway. Int J Nanomed, 2016, 11: 5473-5484

[400] Zhang Y, Xu J, Ruan YC et al. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat Med, 2016, 22: 1160-1169

[401] Singh SS, Roy A, Lee B et al. Study of hMSC proliferation and differentiation on Mg and Mg-Sr containing biphasic β-tricalcium phosphate and amorphous calcium phosphate ceramics. Mater Sci Eng C Mater Biol Appl, 2016, 64: 219-228

[402] Yang F, Yang D, Tu J et al. Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling. Stem Cells, 2011, 29: 981-991

[403] Büttner M, Möller S, Keller M et al. Over-sulfated chondroitin sulfate derivatives induce osteogenic differentiation of hMSC independent of BMP-2 and TGF-β1 signalling. J Cell Physiol, 2013, 228: 330-340

[404] Hu N, Jiang D, Huang E et al. BMP9-regulated angiogenic signaling plays an important role in the osteogenic differentiation of mesenchymal progenitor cells. J Cell Sci, 2013, 126: 532-541

[405] Paul K, Padalhin AR, Linh NT et al. A study of BMP-2-loaded bipotential electrolytic complex around a biphasic calcium phosphate-derived (BCP) scaffold for repair of large segmental bone defect. PLoS One, 2016, 11: e0163708

[406] Yuan Z, Li Q, Luo S et al. PPARγ and Wnt signaling in adipogenic and osteogenic differentiation of mesenchymal stem cells. Curr Stem Cell Res Ther, 2016, 11: 216-225

[407] Wang Q, Chen B, Cao M et al. Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. Biomaterials, 2016, 86: 11-20

[408] Jiang Z, Hua Y. Hydrogen sulfide promotes osteogenic differentiation of human periodontal ligament cells via p38-MAPK signaling pathway under proper tension stimulation. Arch Oral Biol, 2016, 72: 8-13

[409] Yuan X, Cao J, He X et al. Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation. Nat Commun, 2016, 7: 11024

[410] Shi Y, Chen J, Karner CM et al. Hedgehog signaling activates a positive feedback mechanism involving insulin-like growth factors to induce osteoblast differentiation. Proc Natl Acad Sci USA, 2015, 112: 4678-4683

[411] Montgomery SR, Nargizyan T, Meliton V et al. A novel osteogenic oxysterol compound for therapeutic development to promote bone growth: activation of hedgehog signaling and osteogenesis through smoothened binding. J Bone Miner Res, 2014, 29: 1872-1885

[412] Kohn A, Rutkowski TP, Liu Z et al. Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9. Bone Res, 2015, 3: 15021

[413] Hilton MJ, Tu X, Wu X et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med, 2008, 14: 306-314

[414] Engin F, Yao Z, Yang T et al. Dimorphic effects of Notch signaling in bone homeostasis. Nat Med, 2008, 14: 299-305

[415] Rao RR, Ceccarelli J, Vigen ML et al. Effects of hydroxyapatite on endothelial network formation in collagen/fibrin composite hydrogels in vitro and in vivo. Acta Biomater, 2014, 10: 3091-3097

[416] Ritz U, Götz H, Baranowski A et al. Influence of different calcium phosphate ceramics on growth and differentiation of cells in osteoblast-endothelial co-cultures. J Biomed Mater Res B Appl Biomater, 2017, 105: 1950-1962

[417] Mao L, Xia L, Chang J et al. The synergistic effects of Sr and Si bioactive ions on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration. Acta Biomater, 2017, 61: 217-232

[418] van Gastel N, Torrekens S, Roberts SJ et al. Engineering vascularized bone: osteogenic and proangiogenic potential of murine periosteal cells. Stem Cells, 2012, 30: 2460-2471

[419] Kargozar S, Lotfibakhshaiesh N, Ai J et al. Strontium-and cobalt-substituted bioactive glasses seeded with human umbilical cord perivascular cells to promote bone regeneration via enhanced osteogenic and angiogenic activities. Acta Biomater, 2017, 58: 502-514

[420] Shie MY, Chiang WH, Chen IW et al. Synergistic acceleration in the osteogenic and angiogenic differentiation of human mesenchymal stem cells by calcium silicate-graphene composites. Mater Sci Eng C Mater Biol Appl, 2017, 73: 726-735

[421] Li H, Li J, Jiang J et al. An osteogenesis/angiogenesis-stimulation artificial ligament for anterior cruciate ligament reconstruction. Acta Biomater, 2017, 54: 399-410

[422] Wang G, Roohani-Esfahani SI, Zhang W et al. Effects of Sr-HT-Gahnite on osteogenesis and angiogenesis by adipose derived stem cells for critical-sized calvarial defect repair. Sci Rep, 2017, 7: 41135

[423] Kim JJ, El-Fiqi A, Kim HW. Synergetic cues of bioactive nanoparticles and nanofibrous structure in bone scaffolds to stimulate osteogenesis and angiogenesis. ACS Appl Mater Interfaces, 2017, 9: 2059-2073