Progress of three-dimensional macroporous bioactive glass for bone regeneration

Abstract

Bioactive glasses (BGs) are ideal materials for macroporous scaffolds due to their excellent osteoconductive, osteoinductive, biocompatible and biodegradable properties, and their high bone bonding rates. Macroporous scaffolds made from BGs are in high demand for bone regeneration because they can stimulate vascularized bone ingrowth and they enhance bonding between scaffolds and surrounding tissues. Engineering BG/biopolymers (BP) composites or hybrids may be a good way to prepare macroporous scaffolds with excellent properties. This paper summarizes the progress in the past few years in preparing three-dimensional macroporous BG and BG/BP scaffolds for bone regeneration. Since the brittleness of BGs is a major problem in developing macroporous scaffolds and this limits their use in load bearing applications, the mechanical properties of macroporous scaffolds are particularly emphasized in this review.

Key words： bioactive glass; biopolymer; bone regeneration; macroporous scaffolds; tissue engineering

Acknowledgments

This project was Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

References

1 Hench L L, Thompson I. Twenty-first century challenges for biomaterials. Journal of the Royal Society, Interface, 2010, 7(Suppl_4): S379–S391

2 Arcos D, Vallet-Regi M. Sol-gel silica-based biomaterials and bone tissue regeneration. Acta Biomaterialia, 2010, 6(8): 2874–2888

3 Boccaccini A R, Keim S, Ma R, Li Y, Zhitomirsky I. Electrophoretic deposition of biomaterials. Journal of the Royal Society, Interface, 2010, 7(Suppl_5): S581–S613

4 Gorustovich A A, Roether J A, Boccaccini A R. Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Engineering Part B: Reviews, 2010, 16(2): 199–207

5 Hertz A, Bruce I J. Inorganic materials for bone repair or replacement applications. Nanomedicine; Nanotechnology, Biology, and Medicine, 2007, 2: 899–918

6 Hench L L, Xynos I D, Polak J M. Bioactive glasses for in situ tissue regeneration. Journal of Biomaterials Science. Polymer Edition, 2004, 15(4): 543–562

7 Hench L L, Splinter R J, Allen W C, Greenlee T K. Bonding mechanisms at the interface of ceramic prosthetic materials. Journal of Biomedical Materials Research, 1971, 5(6): 117–141

8 Hulbert S F, Young F A, Mathews R S, Klawitter J J, Talbert C D, Stelling F H. Potential of ceramic materials as permanently skeletal prostheses. Journal of Biomedical Materials Research, 1970, 4(3): 433–456

9 Gauthier O, Bouler J M, Aguado E, Pilet P, Daculsi G. Macroporous biphasic calcium phosphate ceramics: influence of macropore diameter and macroporosity percentage on bone ingrowth. Biomaterials, 1998, 19(1-3): 133–139

10 Hutmacher D W. Scaffold design and fabrication technologies for engineering tissues—state of the art and future perspectives. Journal of Biomaterials Science. Polymer Edition, 2001, 12(1): 107–124

11 Guarino V, Causa F, Ambrosio L. Bioactive scaffolds for bone and ligament tissue. Expert Review of Medical Devices, 2007, 4(3): 405–418

12 Moroni L, De Wijn J R, Van Blitterswijk C A. Integrating novel technologies to fabricate smart scaffolds. Journal of Biomaterials Science. Polymer Edition, 2008, 19(5): 543–572

13 Mourino V, Boccaccini A R. Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. Journal of the Royal Society, Interface, 2010, 7(43): 209–227

14 Baroli B. From natural bone grafts to tissue engineering therapeutics: brainstorming on pharmaceutical formulative requirements and challenges. Journal of Pharmaceutical Sciences, 2009, 98(4): 1317–1375

15 Habraken W, Wolke J G C, Jansen J A. Ceramic composites as matrices and scaffolds for drug delivery in tissue engineering. Advanced Drug Delivery Reviews, 2007, 59(4-5): 234–248

16 Lee S H, Shin H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Advanced Drug Delivery Reviews, 2007, 59(4-5): 339–359

17 Chung H J, Park T G. Surface engineered and drug releasing pre-fabricated scaffolds for tissue engineering. Advanced Drug Delivery Reviews, 2007, 59(4-5): 249–262

18 Ginebra M P, Traykova T, Planell J A. Calcium phosphate cements as bone drug delivery systems: a review. Journal of Controlled Release, 2006, 113(2): 102–110

19 Seeherman H, Wozney J M. Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine & Growth Factor Reviews, 2005, 16(3): 329–345

20 Saltzman W M, Olbricht W L. Building drug delivery into tissue engineering. Nature Reviews. Drug Discovery, 2002, 1(3): 177–186

21 Stevens M M, George J H. Exploring and engineering the cell surface interface. Science, 2005, 310(5751): 1135–1138

22 Rezwan K, Chen Q Z, Blaker J J, Boccaccini A R. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials, 2006, 27(18): 3413–3431

23 Li R, Clark A E, Hench L L. An investigation of bioactive glass powders by sol-gel processing. Journal of Applied Biomaterials, 1991, 2(4): 231–239

24 Jones J R, Lin S, Yue S, Lee P D, Hanna J V, Smith M E, Newport R J. Bioactive glass scaffolds for bone regeneration and their hierarchical characterisation. Journal of Engineering in Medicine,2010, 224(12): 1373–1387

25 Qiu D, Martin R A, Knowles J C, Smith M E, Newport R J. A comparative study of the structure of sodium borophosphates made by sol-gel and melt-quench methods. Journal of Non-Crystalline Solids, 2010, 356(9-10): 490–494

26 Li A, Wang D, Xiang J, Newport R J, Reinholdt M X, Mutin P H, Vantelon D, Bonhomme C, Smith M E, Laurencin D, Qiu D. Insights into new calcium phosphosilicate xerogels using an advanced characterization methodology. Journal of Non-Crystalline Solids, 2011, 357(19-20): 3548–3555

27 Qiu D, Guerry P, Knowles J C, Smith M E, Newport R J. Formation of functional phosphosilicate gels from phytic acid and tetraethyl orthosilicate. Journal of Sol-Gel Science and Technology, 2008, 48(3): 378–383

28 Li A, Qiu D. Phytic acid derived bioactive CaO-P₂O₅-SiO₂ gel-glasses. Journal of Materials Science. Materials in Medicine, 2011, 22(12): 2685–2691

29 Brink M. The influence of alkali and alkaline earths on the working range for bioactive glasses. Journal of Biomedical Materials Research, 1997, 36(1): 109–117

30 Vitale-Brovarone C, Verne E, Robiglio L, Appendino P, Bassi F, Martinasso G, Muzio G, Canuto R. Development of glass-ceramic scaffolds for bone tissue engineering: characterisation, proliferation of human osteoblasts and nodule formation. Acta Biomaterialia, 2007, 3(2): 199–208

31 Liu X, Rahaman M N, Fu Q A. Oriented bioactive glass (13-93) scaffolds with controllable pore size by unidirectional freezing of camphene-based suspensions: microstructure and mechanical response. Acta Biomaterialia, 2011, 7(1): 406–416

32 Vitale-Brovarone C, Di Nunzio S, Bretcanu O, Verne E. Macroporous glass-ceramic materials with bioactive properties. Journal of Materials Science. Materials in Medicine, 2004, 15(3): 209–217

33 Saboori A, Sheikhi M, Moztarzadeh F, Rabiee M, Hesaraki S, Tahriri M, Nezafati N. Sol-gel preparation, characterisation and in vitro bioactivity of Mg containing bioactive glass. Advances in Applied Ceramics, 2009, 108(3): 155–161

34 Perez-Pariente J, Balas F, Roman J, Salinas A J, Vallet-Regi M. Influence of composition and surface characteristics on the in vitro bioactivity of SiO₂-CaO-P₂O₅-MgO sol-gel glasses. Journal of Biomedical Materials Research, 1999, 47: 170–175

35 Salinas A J, Roman J, Vallet-Regi M, Oliveira J M, Correia R N, Fernandes M H. In vitro bioactivity of glass and glass-ceramics of the 3CaO center dot P₂O₅-CaO center dot SiO₂-CaO center dot MgO center dot 2SiO(2) system. Biomaterials, 2000, 21: 251–257

36 Saboori A, Rabiee M, Mutarzadeh F, Sheikhi M, Tahriri M, Karimi M. Synthesis, characterization and in vitro bioactivity of sol-gel-derived SiO₂-CaO-P₂O₅-MgO bioglass. Mater Sci Eng C Biomim Supramol Syst, 2009, 29(1): 335–340

37 Jones J R, Ehrenfried L M, Saravanapavan P, Hench L L. Controlling ion release from bioactive glass foam scaffolds with antibacterial properties. Journal of Materials Science. Materials in Medicine, 2006, 17(11): 989–996

38 Vitale-Brovarone C, Miola M, Alagna C B, Verne E. 3D-glass-ceramic scaffolds with antibacterial properties for bone grafting. Chemical Engineering Journal, 2008, 137(1): 129–136

39 Courtheoux L, Lao J, Nedelec J M, Jallot E. Controlled bioactivity in zinc-doped sol-gel-derived binary bioactive glasses. Journal of Physical Chemistry C, 2008, 112(35): 13663–13667

40 Bini M, Grandi S, Capsoni D, Mustarelli P, Saino E, Visai L. SiO₂-P₂O₅-CaO glasses and glass-ceramics with and without ZnO: relationships among composition, microstructure, and bioactivity. Journal of Physical Chemistry C, 2009, 113(20): 8821–8828

41 Lao J, Jallot E, Nedelec J M. Strontium-delivering glasses with enhanced bioactivity: a new biomaterial for antiosteoporotic applications? Chemistry of Materials, 2008, 20(15): 4969–4973

42 Nakamura T, Yamamuro T, Higashi S, Kokubo T, Itoo S. A new glass-ceramic for bone-replacement-evaluation of its bonding to bone tissue. Journal of Biomedical Materials Research, 1985, 19(6): 685–698

43 Ono K, Yamamuro T, Nakamura T, Kokubo T. Mechanical-properties of bone after implantation of apatite wollastonite containing glass ceramic fibrin mixture. Journal of Biomedical Materials Research, 1990, 24(1): 47–63

44 Kawanabe K, Iida H, Matsusue Y, Nishimatsu H, Kasai R, Nakamura T. A-W glass ceramic as a bone substitute in cemented hip arthroplasty-15 hips followed 2-10 years. Acta Orthopaedica, 1998, 69(3): 237–242

45 Yang W, Zhou D, Yin G, Zheng C. Research and development of A-W bioactive glass ceramic. Journal of Biomedical Engineer, 2003, 20(3): 541–545 (in Chinese)

46 Yang W, Zhou D, Yin G, Chen H, Xiao B, Zhang Y. Study on a new type of apatite/wollastonite porous bioactive glass-ceramic. Journal of Biomedical Engineer, 2004, 21: 913–916 (in Chinese)

47 Shinzato S, Kobayashi M, Mousa W F, Kamimura M, Neo M, Kitamura Y, Kokubo T, Nakamura T. Bioactive polymethyl methacrylate-based bone cement: comparison of glass beads, apatite- and wollastonite-containing glass-ceramic, and hydroxyapatite fillers on mechanical and biological properties. Journal of Biomedical Materials Research, 2000, 51(2): 258–272

48 Juhasz J A, Best S M, Brooks R, Kawashita M, Miyata N, Kokubo T, Nakamura T, Bonfield W. Mechanical properties of glass-ceramic A-W-polyethylene composites: effect of filler content and particle size. Biomaterials, 2004, 25(6): 949–955

49 Van de Velde K, Kiekens P. Biopolymers: overview of several properties and consequences on their applications. Polymer Testing, 2002, 21(4): 433–342

50 Suyatma N E, Tighzert L, Copinet A, Coma V. Effects of hydrophilic plasticizers on mechanical, thermal, and surface properties of chitosan films. Journal of Agricultural and Food Chemistry, 2005, 53(10): 3950–3957

51 Wang Y, Qiu D, Cosgrove T, Denbow M L. A small-angle neutron scattering and rheology study of the composite of chitosan and gelatin. Colloids and Surfaces B: Biointerfaces, 2009, 70: 254–258

52 Arvanitoyannis I, Kolokuris I, Nakayama A, Yamamoto N, Aiba S. Physico-chemical studies of chitosan-poly(vinyl alcohol) blends plasticized with sorbitol and sucrose. Carbohydrate Polymers, 1997, 34(1-2): 9–19

53 Van Vlierberghe S, Dubruel P, Schacht E. Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review. Biomacromolecules, 2011, 12(5): 1387–1408

54 Suyatma N E, Copinet A, Tighzert L, Coma V. Mechanical and barrier properties of biodegradable films made from chitosan and poly (lactic acid) blends. Journal of Polymers and the Environment, 2004, 12(1): 1–6

55 Sarasam A, Madihally S V. Characterization of chitosan-polycaprolactone blends for tissue engineering applications. Biomaterials, 2005, 26(27): 5500–5508

56 Santos C, Seabra P, Veleirinho B, Delgadillo I, da Silva J A L. Acetylation and molecular mass effects on barrier and mechanical properties of shortfin squid chitosan membranes. European Polymer Journal, 2006, 42(12): 3277–3285

57 Costa E S, Barbosa-Stancioli E F, Mansur A A P, Vasconcelos W L, Mansur H S. Preparation and characterization of chitosan/poly(vinyl alcohol) chemically crosslinked blends for biomedical applications. Carbohydrate Polymers, 2009, 76(3): 472–481

58 Khan M, Ferdous S, Mustafa A I. Improvement of physico-mechanical properties of chitosan films by photocuring with acrylic monomers. Journal of Polymers and the Environment, 2005, 13(2): 193–201

59 Ji B, Gao H. Mechanical properties of nanostructure of biological materials. Journal of the Mechanics and Physics of Solids, 2004, 52(9): 1963–1990

60 Sionkowska A, Wisniewski M, Skopinska J, Poggi G F, Marsano E, Maxwell C A, Wess T J. Thermal and mechanical properties of UV irradiated collagen/chitosan thin films. Polymer Degradation & Stability, 2006, 91(12): 3026–3032

61 Saito H, Murabayashi S, Mitamura Y, Taguchi T. Characterization of alkali-treated collagen gels prepared by different crosslinkers. Journal of Materials Science. Materials in Medicine, 2008, 19(3): 1297–1305

62 Sheu M T, Huang J C, Yeh G C, Ho H O. Characterization of collagen gel solutions and collagen matrices for cell culture. Biomaterials, 2001, 22(13): 1713–1719

63 Yang L, Van der Werf K O, Fitie C F C, Bennink M L, Dijkstra P J, Feijen J. Mechanical properties of native and cross-linked type I collagen fibrils. Biophysical Journal, 2008, 94(6): 2204–2211

64 van der Rijt J A J, van der Werf K O, Bennink M L, Dijkstra P J, Feijen J. Micromechanical testing of individual collagen fibrils. Macromolecular Bioscience, 2006, 6(9): 697–702

65 Sionkowska A, Skopinska-Wisniewska J, Gawron M, Kozlowska J, Planecka A. Chemical and thermal cross-linking of collagen and elastin hydrolysates. International Journal of Biological Macromolecules, 2010, 47(4): 570–577

66 Nam K, Kimura T, Kishida A. Preparation and characterization of cross-linked collagen-phospholipid polymer hybrid gels. Biomaterials, 2007, 28(1): 1–8

67 Liu W, Deng C, McLaughlin C R, Fagerholm P, Lagali N S, Heyne B, Scaiano J C, Watsky M A, Kato Y, Munger R, Shinozaki N, Li F F, Griffith M. Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes. Biomaterials, 2009, 30(8): 1551–1559

68 Yamauchi K, Takeuchi N, Kurimoto A, Tanabe T. Films of collagen crosslinked by S-S bonds: preparation and characterization. Biomaterials, 2001, 22(8): 855–863

69 Lim L T, Mine Y, Tung M A. Barrier and tensile properties of transglutaminase cross-linked gelatin films as affected by relative humidity, temperature, and glycerol content. Journal of Food Science, 1999, 64(4): 616–622

70 Usta M, Piech D L, MacCrone R K, Hillig W B. Behavior and properties of neat and filled gelatins. Biomaterials, 2003, 24(1): 165–172

71 de Carvalho R A, Grosso C R F. Characterization of gelatin based films modified with transglutaminase, glyoxal and formaldehyde. Food Hydrocolloids, 2004, 18(5): 717–722

72 Cao N, Fu Y, He J. Mechanical properties of gelatin films cross-linked, respectively, by ferulic acid and tannin acid. Food Hydrocolloids, 2007, 21(4): 575–584

73 Fakirov Z S. Anbar T, Boz B, Bahar I, Evstatiev M, Apostolov A A, Mark J E, Kloczkowski A. Mechanical properties and transition temperatures of cross-linked oriented gelatin: 1.Static and dynamic mechanical properties of cross-linked gelatin. Colloid & Polymer Science, 1996, 274: 334–341

74 Santin M, Huang S J, Iannace S, Ambrosio L, Nicolais L, Peluso G. Synthesis and characterization of a new interpenetrated poly(2-hydroxyethylmethacrylate)-gelatin composite polymer. Biomaterials, 1996, 17(15): 1459–1467

75 Vemuri S. A screening technique to study the mechanical strength of gelatin formulations. Drug Development and Industrial Pharmacy, 2000, 26(10): 1115–1120

76 Bigi A, Bracci B, Cojazzi G, Panzavolta S, Roveri N. Drawn gelatin films with improved mechanical properties. Biomaterials, 1998, 19(24): 2335–2340

77 Bigi A, Cojazzi G, Panzavolta S, Rubini K, Roveri N. Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking. Biomaterials, 2001, 22(8): 763–768

78 Yakimets I, Wellner N, Smith A C, Wilson R H, Farhat I, Mitchell J. Mechanical properties with respect to water content of gelatin films in glassy state. Polymer, 2005, 46(26): 12577–12585

79 Lee K Y, Shim J, Lee H G. Mechanical properties of gellan and gelatin composite films. Carbohydrate Polymers, 2004, 56(2): 251–254

80 Bigi A, Panzavolta S, Rubini K. Relationship between triple-helix content and mechanical properties of gelatin films. Biomaterials, 2004, 25(25): 5675–5680

81 Gómez-Guillén M C, Perez-Mateos M, Gomez-Estaca J, Lopez-Caballero E, Gimenez B, Montero P. Fish gelatin: a renewable material for developing active biodegradable films. Trends in Food Science & Technology, 2009, 20(1): 3–16

82 Arvanitoyannis I, Nakayama A, Aiba S I. Edible films made from hydroxypropyl starch and gelatin and plasticized by polyols and water. Carbohydrate Polymers, 1998, 36(2-3): 105–119

83 Arvanitoyannis I S, Nakayama A, Aiba S I. Chitosan and gelatin based edible films: state diagrams, mechanical and permeation properties. Carbohydrate Polymers, 1998, 37(4): 371–382

84 Park J W, Scott Whiteside W, Cho S Y. Mechanical and water vapor barrier properties of extruded and heat-pressed gelatin films. LWT- Food Science and Technology, 2008, 41(4): 692–700

85 Koob T J, Hernandez D J. Mechanical and thermal properties of novel polymerized NDGA-gelatin hydrogels. Biomaterials, 2003, 24(7): 1285–1292

86 Karageorgiou V, Kaplan D. Porosity of 3D biornaterial scaffolds and osteogenesis. Biomaterials, 2005, 26(27): 5474–5491

87 Jones J R, Ehrenfried L M, Hench L L. Optimising bioactive glass scaffolds for bone tissue engineering. Biomaterials, 2006, 27(7): 964–973

88 FitzGerald V, Martin R A, Jones J R, Qiu D, Wetherall K M, Moss R M, Newport R J. Bioactive glass sol-gel foam scaffolds: Evolution of nanoporosity during processing and in situ monitoring of apatite layer formation using small- and wide-angle X-ray scattering. Journal of Biomedical Materials Research. Part A, 2009, 91A(1): 76–83

89 Wu Z Y, Hill R G, Yue S, Nightingale D, Lee P D, Jones J R. Melt-derived bioactive glass scaffolds produced by a gel-cast foaming technique. Acta Biomaterialia, 2011, 7(4): 1807–1816

90 Chen Q Z Z, Thompson I D, Boccaccini A R. 45S5 Bioglass®-derived glass-ceramic scaffolds for bone tissue engineering. Biomaterials, 2006, 27(11): 2414–2425

91 Liu X, Huang W H, Fu H L, Yao A H, Wang D P, Pan H B, Lu W W. Bioactive borosilicate glass scaffolds: improvement on the strength of glass-based scaffolds for tissue engineering. Journal of Materials Science. Materials in Medicine, 2009, 20(1): 365–372

92 Xue M, Feng D G, Li G D, Yang W Z, Zhou D L. Preparation of porous apatite-wollastonite bioactive glass ceramic (AW-GC) by dipping with polymer foams. Chinese Journal of Inorganic Chemistry, 2007, 23: 708–712

93 Cao B, Zhou D, Xue M, Li G, Yang W, Long Q, Ji L. Study on surface modification of porous apatite-wollastonite bioactive glass ceramic scaffold. Applied Surface Science, 2008, 255(2): 505–508

94 Baino F, Verne E, Vitale-Brovarone C. 3-D high-strength glass-ceramic scaffolds containing fluoroapatite for load-bearing bone portions replacement. Materials Science and Engineering: C, 2009, 29(6): 2055–2062

95 Bellucci D, Cannillo V, Sola A, Chiellini F, Gazzarri M, Migone C. Macroporous Bioglass®-derived scaffolds for bone tissue regeneration. Ceramics International, 2011, 37(5): 1575–1585

96 Yan H, Zhang K, Blanford C F, Francis L F, Stein A. In vitro hydroxycarbonate apatite mineralization of CaO-SiO₂ sol-gel glasses with a three-dimensionally ordered macroporous structure. Chemistry of Materials, 2001, 13(4): 1374–1382

97 Yan P H, Wang J Q, Ou J F, Li Z P, Lei Z Q, Yang S R. Synthesis and characterization of three-dimensional ordered mesoporous-macroporous bioactive glass. Materials Letters, 2010, 64(22): 2544–2547

98 Wei G F, Yan X X, Yi J, Zhao L Z, Zhou L, Wang Y H, Yu C Z. Synthesis and in-vitro bioactivity of mesoporous bioactive glasses with tunable macropores. Microporous and Mesoporous Materials, 2011, 143(1): 157–165

99 Hajiali H, Karbasi S, Hosseinalipour M, Rezaie H R. Preparation of a novel biodegradable nanocomposite scaffold based on poly (3-hydroxybutyrate)/bioglass nanoparticles for bone tissue engineering. Journal of Materials Science, 2010, 21(7): 2125–2133

100 Ryszkowska J L, Auguscik M, Sheikh A, Boccaccini A R. Biodegradable polyurethane composite scaffolds containing Bioglass® for bone tissue engineering. Composites Science and Technology, 2010, 70(13): 1894–1908

101 Mozafari M, Moztarzadeh F, Rabiee M, Azami M, Maleknia S, Tahriri M, Moztarzadeh Z, Nezafati N. Development of macroporous nanocomposite scaffolds of gelatin/bioactive glass prepared through layer solvent casting combined with lamination technique for bone tissue engineering. Ceramics International, 2010, 36(8): 2431–2439

102 Hong Z K, Reis R L, Mano J F. Preparation and in vitro characterization of scaffolds of poly(L-lactic acid) containing bioactive glass ceramic nanoparticles. Acta Biomaterialia, 2008, 4(5): 1297–1306

103 Barroca N, Daniel-da-Silva A L, Vilarinho P M, Fernandes M H V. Tailoring the morphology of high molecular weight PLLA scaffolds through bioglass addition. Acta Biomaterialia, 2010, 6(9): 3611–3620

104 Fabbri P, Cannillo V, Sola A, Dorigato A, Chiellini F. Highly porous polycaprolactone-45S5 Bioglass® scaffolds for bone tissue engineering. Composites Science and Technology, 2010, 70(13): 1869–1878

105 Minaberry Y, Jobbagy M. Macroporous bioglass scaffolds prepared by coupling sol-gel with freeze drying. Chemistry of Materials, 2011, 23(9): 2327–2332

106 Doiphode N D, Huang T S, Leu M C, Rahaman M N, Day D E. Freeze extrusion fabrication of 13-93 bioactive glass scaffolds for bone repair. Journal of Materials Science. Materials in Medicine, 2011, 22(3): 515–523

107 Garcia A, Izquierdo-Barba I, Colilla M, de Laorden C L, Vallet-Regí M. Lopez de laorden C, Vallet-Regi M. Preparation of 3-D scaffolds in the SiO₂-P₂O₅ system with tailored hierarchical meso-macroporosity. Acta Biomaterialia, 2011, 7(3): 1265–1273

108 Yun H S, Kim S E, Park E K. Bioactive glass-poly(epsilon-caprolactone) composite scaffolds with 3 dimensionally hierarchical pore networks. Materials Science and Engineering: C, 2011, 31(2): 198–205

109 Valliant E M, Jones J R. Softening bioactive glass for bone regeneration: sol-gel hybrid materials. Soft Matter, 2011, 7(11): 5083–5095

110 Mahony O, Tsigkou O, Ionescu C, Minelli C, Ling L, Hanly R, Smith M E, Stevens M M, Jones J R. Silica-gelatin hybrids with tailorable degradation and mechanical properties for tissue regeneration. Advanced Functional Materials, 2010, 20(22): 3835–3845

111 Pereira M M, Jones J R, Orefice R L, Hench L L. Preparation of bioactive glass-polyvinyl alcohol hybrid foams by the sol-gel method. Journal of Materials Science. 2005, 16(11): 1045–1050

112 Costa H S, Rocha M F, Andrade G I, Barbosa-Stancioli E F, Pereira M M, Orefice R L, Vasconcelos W L, Mansur H S. Sol-gel derived composite from bioactive glass-polyvinyl alcohol. Journal of Materials Science, 2008, 43(2): 494–502

113 Costa H S, Stancioli E F B, Pereira M M, Orefice R L, Mansur H S. Synthesis, neutralization and blocking procedures of organic/inorganic hybrid scaffolds for bone tissue engineering applications. Journal of Materials Science, 2009, 20(2): 529–535

114 de Oliveira A A R, Ciminelli V, Dantas M S S, Mansur H S, Pereira M M. Acid character control of bioactive glass/polyvinyl alcohol hybrid foams produced by sol-gel. Journal of Sol-Gel Science and Technology, 2008, 47(3): 335–346

115 Costa H S, Mansur A A P, Pereira M M, Mansur H S. Engineered hybrid scaffolds of poly(vinyl alcohol)/bioactive glass for potential bone engineering applications: synthesis, characterization, cytocompatibility, and degradation. Journal of Nanomaterials, 2012, 2012: 1–16

116 Lin S, Ionescu C, Pike K J, Smith M E, Jones J R. Nanostructure evolution and calcium distribution in sol-gel derived bioactive glass. Journal of Materials Chemistry, 2009, 19(9): 1276–1282