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Macro-, micro- and mesoporous materials for tissue engineering applications

1 Tissue Bioengineering Laboratory, DEPeI-FO, Universidad Nacional Autónoma de México, Mexico
2 Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, Italy

Topical Section: Porous Materials

The design of three-dimensional materials with multiscale pore architecture currently represents a relevant challenge for tissue engineering. In the last three decades, degradable and resorbable biomaterials have been variously manipulated to generate macro/micro/mesoporous templates able to guide and facilitate basic cell activities concurring to the sequence of events triggering in vitro and in vivo regeneration of tissues. In this context, an accurate control of porosity features (i.e., pore size and distribution, pore interconnectivity) as a function of the peculiar properties of constituent materials is extremely demanded to not compromise scaffold mechanical properties and stability and replying local micro-environmental features from structural and functional point of view. Herein, an extended overview of consolidated and emerging approaches to design macro-, micro-, and mesoporous materials has been reported, underlining among differences mainly due to the peculiar properties of used biomaterials (i.e., polymers, ceramics, composites).
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1. Barrilleaux B, Phinney DG, Prockop DJ, et al. (2006) Review: ex vivo engineering of living tissues with adult stem cells. Tissue Eng 12: 3007–3019.    

2. Hutmacher DW (2000) Scaffolds in tissue engineering bone and cartilage. Biomaterials 21: 2529–2543.    

3. Lee J, Guarino V, Gloria A, et al. (2010) Regeneration of Achilles' tendon: the role of dynamic stimulation for enhanced cell proliferation and mechanical properties. J Biomat Sci-Polym E 21: 1173–1190.    

4. Veronesi F, Giavaresi G, Guarino V, et al. (2015) Bioactivity and bone healing properties of biomimetic porous composite scaffold: in vitro and in vivo studies. J Biomed Mater Res A 103: 2932–2941.    

5. Guarino V, Galizia M, Alvarez-Perez MA, et al. (2015) Improving surface and transport properties of macroporous hydrogels for bone regeneration. J Biomed Mater Res A 103: 1095–1105.    

6. Guarino V, Ambrosio L (2010) Temperature-driven processing techniques for manufacturing fully interconnected porous scaffolds in bone tissue engineering. P I Mech Eng H 224: 1389–1400.    

7. Liu X, Ma PX (2009) Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds. Biomaterials 30: 4094–4103.    

8. Gong S, Wang H, Sun Q, et al. (2006) Mechanical properties and in vitro biocompatibility of porous zein scaffolds. Biomaterials 27: 3793–3799.    

9. Chiu YC, Larson JC, Isom Jr. A, et al. (2010) Generation of porous poly(ethylene glycol) hydrogels by salt leaching. Tissue Eng C 16: 905–912.

10. De Nardo L, Bertoldi S, Cigada A, et al. (2012) Preparation and characterization of shape memory polymer scaffolds via solvent casting/particulate leaching. J Appl Biomater Func 2: 119–126.

11. Intranuovo F, Gristina R, Brun F, et al. (2014) Plasma modification of PCL porous scaffolds fabricated by solvent-casting/particulate-leaching for tissue engineering. Plasma Process Polym 11: 184–195.    

12. Hou Q, Grijpma DW, Feijen J (2003) Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. Biomaterials 24: 1937–1947.    

13. Yoon JJ, Song SH, Lee DS, et al. (2004) Immobilization of cell adhesive RGD peptide onto the surface of highly porous biodegradable polymer scaffolds fabricated by a gas foaming/salt leaching method. Biomaterials 25: 5613–5620.    

14. Kim TK, Yoon JJ, Lee DS, et al. (2006) Gas foamed open porous biodegradable polymeric microspheres. Biomaterials 27: 152–159.    

15. Kim BS, Kim EJ, Choi JS, et al. (2014) Human collagen-based multilayer scaffolds for tendon-to-bone interface tissue engineering. J Biomed Mater Res A 102: 4044–4054.    

16. Sultana N, Wang M (2008) Fabrication of HA/PHBV composite scaffolds through the emulsion freezing/freeze-drying process and characterisation of the scaffolds. J Mater Sci-Mater M 19: 2555–2561.    

17. Xiong Z, Yan Y, Zhang R, et al. (2001) Fabrication of porous poly(L-lactic acid) scaffolds for bone tissue engineering via precise extrusion. Scripta Mater 45: 773–779.    

18. Seck TM, Melchels FPW, Feijen J, et al. (2010) Designed biodegradable hydrogel structures prepared by stereolithography using poly(ethylene glycol)/poly(d,l-lactide)-based resins. J Control Release 148: 34–41.    

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

20. Yan M, Tian X, Peng G, et al. (2017) Hierarchically porous materials prepared by selective laser sintering. Mater Design 135: 62–68.    

21. Liverani L, Guarino V, La Carrubba V, et al. (2017) Porous biomaterials and scaffolds for tissue engineering, In: Narayan R, Encyclopedia of Biomedical Engineering.

22. Granados-Hernández MV, Serrano-Bello J, Montesinos JJ, et al. (2018) In vitro and in vivo biological characterization of poly(lactic acid) fiber scaffolds synthesized by air jet spinning. J Biomed Mater Res B 106: 2435–2446.    

23. Guarino V, Ambrosio L (2016) Electrofluidodynamics: exploring a new toolbox to design biomaterials for tissue regeneration and degeneration. Nanomedicine 11: 1515–1518.    

24. Blaker JJ, Knowles JC, Day RM (2008) Novel fabrication techniques to produce microspheres by thermally induced phase separation for tissue engineering and drug delivery. Acta Biomater 4: 264–272.    

25. Manferdini C, Guarino V, Zini N, et al. (2010) Mineralization occurs faster on a new biomimetic hyaluronic acid-based scaffold. Biomaterials 31: 3986–3996.

26. Guarino V, Lewandowska M, Bil M, et al. (2010) Morphology and degradation properties of PCL/HYAFF11® composite scaffolds with multi-scale degradation rate. Compos Sci Technol 70: 1826–1837.    

27. Salerno A, Guarino V, Oliviero O, et al. (2016) Bio-safe processing of polylactic-co-caprolactone and polylactic acid blends to fabricate nanofibrous porous scaffolds for tissue engineering. Mat Sci Eng C-Mater 63: 512–521.    

28. Luciani A, Guarino V, Ambrosio L, et al. (2019) Solvent and melting induced microspheres sintering techniques : a comparative study of morphology and mechanical properties. J Mater Sci-Mater M 22: 2019–2028.

29. Guarino V, Causa F, Salerno A, et al. (2008) Design and manufacture of microporous polymeric materials with hierarchal complex structure for biomedical application. Mater Sci Technol 24: 1111–1117.    

30. Whang K, Healy KE (1995) A novel method scaffolds to fabricate bioabsorbable. Polymer 36: 837–842.    

31. Ma PX, Zhang R (1998) Synthetic nano-scale fibrous extracellular matrix. J Biomed Mater Res 46: 60–72.

32. Sohn DG, Hong MW, Kim YY, et al. (2015) Fabrication of dual-pore scaffolds using a combination of wire-networked molding (WNM) and non-solvent induced phase separation (NIPS) techniques. J Bionic Eng 12: 565–574.    

33. Shin KC, Kim BS, Kim JH, et al. (2005) A facile preparation of highly interconnected macroporous PLGA scaffolds by liquid–liquid phase separation II. Polymer 46: 3801–3808.    

34. Li S, Chen X, Li M (2011) Effect of some factors on fabrication of poly(L-lactic acid) microporous foams by thermally induced phase separation using N,N-dimethylacetamide as solvent. Prep Biochem Biotech 41: 53–72.

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

36. Forbes SJ, Rosenthal N (2014) Preparing the ground for tissue regeneration : from mechanism to therapy. Nat Med 20: 857–869.    

37. Hollister SJ (2005) Porous scaffold design for tissue engineering. Nat Mater 4: 518–524.    

38. Skoog SA, Goering PL, Narayan RJ (2014) Stereolithography in tissue engineering. J Mater Sci-Mater M 25: 845–856.    

39. Ko SH, Pan H, Grigoropoulos CP (2007) All-inkjet-printed flexible electronics fabrication on a polymer substrate by low-temperature high-resolution selective laser sintering of metal nanoparticles. Nanotechnology 18: 345202.    

40. Hutmacher DW (2001) Scaffold design and fabrication technologies for engineering tissues-state of the art and future perspectives. J Biomat Sci-Polym E 12: 107–124.    

41. Khademhosseini A, Bong GC (2009) Microscale technologies for tissue engineering. 2009 IEEE/NIH Life Science Systems and Applications Workshop, Bethesda, MD, USA, 56–57.

42. Fischbach C, Chen R, Matsumoto T, et al. (2007) Engineering tumors with 3D scaffolds. Nat Methods 4: 855–860.    

43. Rutz AL, Hyland KE, Jakus AE, et al. (2015) A multimaterial bioink method for 3D printing tunable, cell-compatible hydrogels. Adv Mater 27: 1607–1614.    

44. Guarino V, Cirillo V, Altobelli R, et al. (2015) Polymer-based platforms by electric field-assisted techniques for tissue engineering and cancer therapy. Expert Rev Med Devic 12: 113–129.    

45. Guaccio A, Guarino V, Alvarez-Perez MA, et al. (2011) Influence of electrospun fiber mesh size on hMSC oxygen metabolism in 3D collagen matrices: Experimental and theoretical evidences. Biotechnol Bioeng 108: 1965–1976.    

46. Cirillo V, Guarino V, Alvarez-Perez MA, et al. (2014) Optimization of fully aligned bioactive electrospun fibers for "in vitro" nerve guidance. J Mater Sci-Mater M 25: 2323–2332.    

47. Pires LR, Guarino V, Oliveira MJ, et al. (2016) Ibuprofen-loaded poly(trimethylene carbonate-co-ε-caprolactone) electrospun fibres for nerve regeneration. J Tissue Eng Regen M 10: E154–E166.    

48. Alvarez-Perez MA, Guarino V, Cirillo V, et al. (2012) In vitro mineralization and bone osteogenesis in poly(ε-caprolactone)/gelatin nanofibers. J Biomed Mater Res A 100: 3008–3019.

49. Cirillo V, Clements BA, Guarino V, et al. (2014) A comparison of the performance of mono- and bi-component electrospun conduits in a rat sciatic model. Biomaterials 35: 8970–8982.    

50. Fasolino I, Guarino V, Cirillo V, et al. (2017) 5-Azacytidine-mediated hMSC behavior on electrospun scaffolds for skeletal muscle regeneration. J Biomed Mater Res A 105: 2551–2561.    

51. Guarino V, Altobelli R, Cirillo V, et al. (2015) Additive electrospraying: a route to process electrospun scaffolds for controlled molecular release. Polym Advan Technol 26: 1359–1369.    

52. Guarino V, Cruz-Maya I, Altobelli R, et al. (2017) Antibacterial platforms via additive electrofluidodynamics for oral treatments. Nanotechology 28: 505303.

53. Slowing II, Vivero-Escoto JL, Wu C, et al. (2008) Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliver Rev 60: 1278–1288.    

54. Vivero-Escoto JL, Slowing II, Trewyn BG, et al. (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6: 1952–1967.    

55. Belmoujahid Y, Bonne M, Scudeller Y, et al. (2015) SBA-15 mesoporous silica as a super insulating material. Eur Phys J Special Topics 224: 1775–1785.    

56. Vargas-Osorio Z, González-Gómez MA, Piñeiro Y, et al. (2017) Novel synthetic routes of large-pore magnetic mesoporous nanocomposites (SBA-15/Fe3O4) as potential multifunctional theranostic nanodevices. J Mater Chem B 5: 9395–9404.    

57. Vargas-Osorio Z, Chanes-Cuevas OA, Pérez-Soria A, et al. (2017) Physicochemical effects of amino- or sulfur-functional groups onto SBA-15 sol-gel synthesized mesoporous ceramic material. Phys Status Solidi C 14: 1600099.

58. Kresge CT, Leonowicz ME, Roth WJ, et al. (1992) Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 359: 710–712.    

59. Vartuli JC, Schmitt KD, Kresge CT, et al. (1994) Effect of surfactant/silica molar ratios on the formation of mesoporous molecular sieves: inorganic mimicry of surfactant liquid-crystal phases and mechanistic implications. Chem Mater 6: 2317–2326.    

60. Kresge CT, Roth WJ (2013) The discovery of mesoporous molecular sieves from the twenty year perspective. Chem Soc Rev 42: 3663–3670.    

61. Feliczak-Guzik A, Jadach B, Piotrowska H, et al. (2016) Synthesis and characterization of SBA-16 type mesoporous materials containing amine groups. Micropor Mesopor Mat 220: 231–238.    

62. Gonzalez G, Sagarzazu A, Cordova A, et al. (2017) Comparative study of two silica mesoporous materials (SBA-16 and SBA-15) modified with a hydroxyapatite layer for clindamycin controlled delivery. Micropor Mesopor Mat 256: 251–261.

63. Chang JS, Chang KLB, Hwang DF, et al. (2007) In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol 41: 2064–2068.    

64. Soler-Illia GJAA, Sanchez C, Lebeau B, et al. (2002) Chemical strategies to design textured materials:  from microporous and mesoporous oxides to nanonetworks and hierarchical structures. Chem Rev 102: 4093–4138.    

65. Eliaz N, Metoki N (2017) Calcium phosphate bioceramics: a review of their history, structure, properties, coating technologies and biomedical applications. Materials 10: 334.    

66. Ambrosio L, Guarino V, Sanginario V, et al. (2012). Injectable calcium phosphate based composites for skeletal bone treatments. Biomed Mater 7: 024113.

67. Guarino V, Ambrosio L (2013) Thermoset composite hydrogels for bone/intervertebral disc interface. Mater Lett 110: 249–252.    

68. Vallet-Regí M, Manzano-García M, Colilla M (2012) Biocompatible and bioactive mesoporous ceramics, In: Vallet-Regí M, Manzano-García M, Colilla M, Biomedical Applications of Mesoporous Ceramics: Drug Delivery, Smart Materials and Bone Tissue Engineering, Boca Raton: CRC Press, 1–66.

69. Samavedi S, Whittington AR, Goldstein AS (2013) Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater 9: 8037–8045.    

70. Ishikawa K (2014) Calcium phosphate cement, In: Ben-Nissan B, Advances in Calcium Phosphate Biomaterials, Springer, 199–227.

71. Ambard AJ, Mueninghoff L (2006) Calcium phosphate cement: review of mechanical and biological properties. J Prosthodont 15: 321–328.    

72. Coti KK, Belowich ME, Liong M, et al. (2009) Mechanised nanoparticles for drug delivery. Nanoscale 1: 16–39.    

73. Vallet-Regi M, Rámila A, del Real RP, et al. (2001) A new property of MCM-41:  drug delivery system. Chem Mater 13: 308–311.    

74. Balas F, Manzano M, Horcajada P, et al. (2006) Confinement and controlled release of bisphosphonates on ordered mesoporous silica-based materials. J Am Chem Soc 128: 8116–8117.    

75. Vallet-Regí M, Ruiz-González L, Izquierdo-Barba I, et al. (2006) Revisiting silica based ordered mesoporous materials: medical applications. J Mater Chem 16: 26–31.    

76. Mourino V, Boccaccini AR (2010) Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. J R Soc Interface 7: 209–227.    

77. Werner J, Sa S (2008) Hierarchical pore structure of calcium phosphate scaffolds by a combination of gel-casting and multiple tape-casting methods. Acta Biomater 4: 913–922.    

78. Vallet-Regí M (2008) Current trends on porous inorganic materials for biomedical applications. Chem Eng J 137: 1–3.    

79. Baeza A, Izquierdo-Barba I, Vallet-Regí M (2010) Biotinylation of silicon-doped hydroxyapatite: a new approach to protein fixation for bone tissue regeneration. Acta Biomater 6: 743–749.    

80. Dorozhkin SV (2015) Calcium orthophosphate-containing biocomposites and hybrid biomaterials for biomedical applications. J Funct Biomater 6: 708–832.    

81. Perez RA, Kim HW, Ginebra MP (2012) Polymeric additives to enhance the functional properties of calcium phosphate cements. J Tissue Eng 3: 2041731412439555.

82. Deb P, Deoghare AB, Borah A, et al. (2018) Scaffold development using biomaterials : A review. Mater Today Proc 5: 12909–12919.    

83. Zarrin A, Moztarzadeh F (2018) Synthesizing and characterizing of gelatin-chitosan-bioactive glass (58s) scaffolds for bone tissue engineering. Silicon 10: 1393–1394.    

84. Wingender B, Bradley P, Saxena N, et al. (2016) Biomimetic organization of collagen matrices to template bone-like microstructures. Matrix Biol 52–54: 384–396.

85. Kang Z, Zhang X, Chen Y, et al. (2017) Preparation of polymer/calcium phosphate porous composite as bone tissue scaffolds. Mat Sci Eng C-Mater 70: 1125–1131.    

86. Xu Y, Gao D, Feng P, et al. (2017) A mesoporous silica composite scaffold : Cell behaviors, biomineralization and mechanical properties. Appl Surf Sci 423: 314–321.    

87. Mondal S, Hoang G, Manivasagan P, et al. (2018) Nano-hydroxyapatite bioactive glass composite scaffold with enhanced mechanical and biological performance for tissue engineering application. Ceram Int 44: 15735–15746.    

88. Guarino V, Scaglione S, Sandri M, et al. (2014) MgCHA particles dispersion in porous PCL scaffolds: in vitro mineralization and in vivo bone formation. J Tissue Eng Regen M 8: 291–303.    

89. Scaglione S, Guarino V, Sandri M, et al. (2012) In vivo lamellar bone formation in fibre coated MgCHA–PCL-composite scaffolds. J Mater Sci-Mater M 23: 117–128.    

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