This review comprehensively summarizes various preparatory methods of polymeric bone scaffolds using conventional and modern advanced methods. Compilations of the various fabrication techniques, specific composition, and the corresponding properties obtained under clearly identified conditions are presented in the commercial formulations of bone scaffolds in current orthopedic use. The gaps and unresolved questions in the existing database, efforts that should be made to address these issues, and research directions are also covered. Polymers are unique synthetic materials primarily used for bone and scaffold applications. Bone scaffolds based on acrylic polymers have been widely used in orthopedic surgery for years. Polymethyl methacrylate (PMMA) is especially known for its widespread applications in bone repair and dental fields. In addition, the PMMA polymers are suitable for carrying antibiotics and for their sustainable release at the site of infection.

1. Turner CH, Wang T, Burr DB. Shear Strength and Fatigue Properties of Human Cortical Bone Determined from Pure Shear Tests. Calcified Tissue International. 2001; 69(6): 373-378. doi: 10.1007/s00223-001-1006-1

2. Lee H, Liao JD, Guo YS, et al. Biomimetic Design for a Dual Concentric Porous Titanium Scaffold with Appropriate Compressive Strength and Cells Affinity. Materials. 2020; 13(15): 3316. doi:

3. 3390/ma13153316

4. Lin JT, Lane JM. Osteoporosis. Clinical Orthopaedics and Related Research. 2004; 425: 126-134. doi: 10.1097/01.blo.0000132404.30139.f2

5. Marcus R, Dempster DW, Cauley JA, Feldman D. Osteoporosis. Academic Press; 2013.

6. Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. The Lancet. 2011; 377: 1276-1287. doi: 10.1016/S0140-6736(10)62349-5

7. Brooks H, Azen S, Gerberg E, et al. Scoliosis. The Journal of Bone & Joint Surgery. 1975; 57(7): 968-972. doi: 10.2106/00004623-197557070-00015

8. MacLennan A. Scoliosis. The British Medical Journal. 1922; 2(3227): 864-866.

9. Rogala EJ, Drummond DS, Gurr J. Scoliosis. The Journal of Bone & Joint Surgery. 1978; 60(2): 173-176. doi: 10.2106/00004623-197860020-00005

10. Calhoun JH, Manring MM. Adult Osteomyelitis. Infectious Disease Clinics of North America. 2005; 19(4): 765-786. doi: 10.1016/j.idc.2005.07.009

11. Lew DP, Waldvogel FA. Osteomyelitis. New England Journal of Medicine. 1997; 336(14): 999-1007. doi: 10.1056/nejm199704033361406

12. Waldvogel FA, Vasey H. Osteomyelitis: The Past Decade. New England Journal of Medicine. 1980; 303(7): 360-370. doi: 10.1056/nejm198008143030703

13. Ramesh N, Moratti SC, Dias GJ. Hydroxyapatite–polymer biocomposites for bone regeneration: A review of current trends. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2017; 106(5): 2046-2057. doi: 10.1002/jbm.b.33950

14. Dimitriou R, Jones E, McGonagle D, et al. Bone regeneration: current concepts and future directions. BMC Medicine. 2011; 9(1). doi: 10.1186/1741-7015-9-66

15. Soucacos PN, Johnson EO, Babis G. An update on recent advances in bone regeneration. Injury. 2008; 39: S1-S4. doi: 10.1016/S0020-1383(08)70009-3

16. Cornell CN, Lane JM. Current Understanding of Osteoconduction in Bone Regeneration. Clinical Orthopaedics and Related Research. 1998; 355S: S267-S273. doi: 10.1097/00003086-199810001-00027

17. Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. European Spine Journal. 2001; 10(0): S96-S101. doi: 10.1007/s005860100282

18. Kuzyk PRT, Schemitsch EH. The basic science of peri-implant bone healing. Indian Journal of Orthopaedics. 2011; 45(2): 108-115. doi: 10.4103/0019-5413.77129

19. Chang BS, Hong KS, Youn HJ, et al. Osteoconduction at porous hydroxyapatite with various pore configurations. Biomaterials. 2000; 21: 1291-1298. doi: 10.1016/S0142-9612(00)00030-2

20. Krishnan MR, Alsharaeh E. Potential removal of benzene-toluene-xylene toxic vapors by nanoporous poly(styrene-r-methylmethacrylate) copolymer composites. Environmental Nanotechnology, Monitoring & Management. 2023; 20: 100860. doi: 10.1016/j.enmm.2023.100860

21. Krishnan MR, Alsharaeh EH. Polymer gel amended sandy soil with enhanced water storage and extended release capabilities for sustainable desert agriculture. Journal of Polymer Science and Engineering. 2023; 6(1): 2892. doi: 10.24294/jpse.v6i1.2892

22. Krishnan MR, Alsharaeh EH. Facile fabrication of thermo-mechanically reinforced polystyrene-graphene nanocomposite aerogel for produced water treatment. Journal of Porous Materials. 2024; 31: 1363-1373. doi: 10.1007/s10934-024-01602-y

23. Krishnan MR, Alsharaeh EH. High-performance functional materials based on polymer nanocomposites—A review. Journal of Polymer Science and Engineering. 2023; 6(1): 3292. doi: 10.24294/jpse.v6i1.3292

24. Krishnan MR, Rajendran V. Sulfonated mesoporous polystyrene-1D multiwall carbon nanotube nanocomposite as potential adsorbent for efficient removal of xylene isomers from aqueous solution. Characterization and Application of Nanomaterials. 2023; 6(2): 3516. doi: 10.24294/can.v6i2.3516

25. Krishnan M, Michal F, Alsoughayer S, et al. Thermodynamic and Kinetic Investigation of Water Absorption by PAM Composite Hydrogel. In: Proceedings of the SPE Kuwait Oil & Gas Show and Conference; 13-16 October 2019; Mishref, Kuwait. doi: 10.2118/198033-ms

26. Krishnan MR, Aldawsari YF, Alsharaeh EH. Three‐dimensionally cross‐linked styrene‐methyl methacrylate‐divinyl benzene terpolymer networks for organic solvents and crude oil absorption. Journal of Applied Polymer Science. 2020; 138(9). doi: 10.1002/app.49942

27. Krishnan MR, Aldawsari Y, Michael FM, et al. 3D-Polystyrene-polymethyl methacrylate/divinyl benzene networks-Epoxy-Graphene nanocomposites dual-coated sand as high strength proppants for hydraulic fracture operations. Journal of Natural Gas Science and Engineering. 2021; 88: 103790. doi: 10.1016/j.jngse.2020.103790

28. Krishnan MR, Aldawsari Y, Michael FM, et al. Mechanically reinforced polystyrene-polymethyl methacrylate copolymer-graphene and Epoxy-Graphene composites dual-coated sand proppants for hydraulic fracture operations. Journal of Petroleum Science and Engineering. 2021; 196: 107744. doi: 10.1016/j.petrol.2020.107744

29. Krishnan M, Chen HY, Ho RM. Switchable structural colors from mesoporous polystyrene films. In: Proceedings of the ACS 252nd. National Meeting; 18-26 August 2016; Philadelphia, Pennsylvania, USA.

30. Krishnan MR, Almohsin A, Alsharaeh EH. Syntheses and fabrication of mesoporous styrene-co-methyl methacrylate-graphene composites for oil removal. Diamond and Related Materials. 2022; 130: 109494. doi: 10.1016/j.diamond.2022.109494

31. Krishnan MR, Omar H, Yazeed Y, et al. Insight into Thermo-Mechanical Enhancement of Polymer Nanocomposites Coated Microsand Proppants for Hydraulic Fracturing. SSRN Electronic Journal. 2022. doi: 10.2139/ssrn.4243574

32. Krishnan MR, Rajendran V, Alsharaeh E. Anti-reflective and high-transmittance optical films based on nanoporous silicon dioxide fabricated from templated synthesis. Journal of Non-Crystalline Solids. 2023; 606: 122198. doi: 10.1016/j.jnoncrysol.2023.122198

33. Krishnan MR, Li W, Alsharaeh EH. Ultra-lightweight Nanosand/Polymer Nanocomposite Materials for Hydraulic Fracturing Operations. SSRN Electronic Journal. 2022. doi: 10.2139/ssrn.4233321

34. Krishnan MR, Omar H, Almohsin A, et al. An overview on nanosilica–polymer composites as high-performance functional materials in oil fields. Polymer Bulletin. 2023; 81(5): 3883-3933. doi: 10.1007/s00289-023-04934-y

35. Krishnan MR, Li W, Alsharaeh EH. Cross-linked polymer nanocomposite networks coated nano sand light-weight proppants for hydraulic fracturing applications. Characterization and Application of Nanomaterials. 2023; 6(2): 3314. doi: 10.24294/can.v6i2.3314

36. Krishnan MR, Almohsin A, Alsharaeh EH. Thermo-Mechanically Reinforced Mesoporous Styrene-Co-Methyl Methacrylate-Graphene Composites for Produced Water Treatment. SSRN Electronic Journal. 2022.

37. Aldosari MA, Alsaud KBB, Othman A, et al. Microwave Irradiation Synthesis and Characterization of Reduced-(Graphene Oxide-(Polystyrene-Polymethyl Methacrylate))/Silver Nanoparticle Nanocomposites and Their Anti-Microbial Activity. Polymers. 2020; 12(5): 1155. doi: 10.3390/polym12051155

38. Krishnan MR, Almohsin A, Alsharaeh EH. Mechanically robust and thermally enhanced sand‐polyacrylamide‐2D nanofiller composite hydrogels for water shutoff applications. Journal of Applied Polymer Science. 2023; 141(7). doi: 10.1002/app.54953

39. Almohsin A, Michal F, Alsharaeh E, et al. Self-Healing PAM Composite Hydrogel for Water Shutoff at High Temperatures: Thermal and Rheological Investigations. In: Proceedings of the SPE Gas & Oil Technology Showcase and Conference; 21-23 October 2019; Dubai, United Arab Emirates. doi: 10.2118/198664-ms

40. Almohsin A, Alsharaeh E, Michael FM, Krishnan MR. Polymer-Nanofiller Hydrogels. US Patent, US11828116B2, 31 October 2023.

41. Almohsin A, Alsharaeh E, Krishnan MR. Polymer-Sand Nanocomposite Lost Circulation Material. US Patent, US11828116B2, 28 November 2023.

42. Almohsin A, Alsharaeh E, Krishnan MR, Alghazali M. Coated Nanosand as Relative Permeability Modifier. US Patent, US11827852B2, 28 November 2023.

43. Almohsin A, Krishnan MR, Alsharaeh E, et al. Preparation and Properties Investigation on Sand-Polyacrylamide Composites with Engineered Interfaces for Water Shutoff Applications. In: Proceedings of the Middle East Oil, Gas and Geosciences Show; 19-21 February 2023; Manama, Bahrain. doi: 10.2118/213481-ms

44. Keishnan MR, Michael FM, Almohsin AM, et al. Thermal and Rheological Investigations on N,N’-Methylenebis Acrylamide Cross-Linked Polyacrylamide Nanocomposite Hydrogels for Water Shutoff Applications. In: Proceedings of the Offshore Technology Conference Asia; 2-6 November 2020; Kuala Lumpur, Malaysia. doi: 10.4043/30123-ms

45. Krishnan MR, Aldawsari YF, Alsharaeh EH. 3D-poly(styrene-methyl methacrylate)/divinyl benzene-2D-nanosheet composite networks for organic solvents and crude oil spill cleanup. Polymer Bulletin. 2021; 79(6): 3779-3802. doi: 10.1007/s00289-021-03565-5

46. Krishnan MR, Lu K, Chiu W, et al. Directed Self‐Assembly of Star‐Block Copolymers by Topographic Nanopatterns through Nucleation and Growth Mechanism. Small. 2018; 14(16). doi: 10.1002/smll.201704005

47. Ho RM, Krishnan MR, Siddique SK, Chien YC. Method for Fabricating Nanoporous Polymer Thin Film and Corresponding Method for Fabricating Nanoporous Thin Film. US Patent, US11059205B2, 13 July 2021.

48. Alsharaeh EH, Krishnan MR. Method of Making Mutlilayer Soil with Property for Extended Release Water for Desert Agriculture. US Patent, US10772265B1, 15 September 2020.

49. Tasleem S, Bongu CS, Krishnan MR, et al. Navigating the hydrogen prospect: A comprehensive review of sustainable source-based production technologies, transport solutions, advanced storage mechanisms, and CCUS integration. Journal of Energy Chemistry. 2024; 97: 166-215. doi: 10.1016/j.jechem.2024.05.022

50. Michael FM, Krishnan MR, Fathima A, et al. Zirconia/graphene nanocomposites effect on the enhancement of thermo-mechanical stability of polymer hydrogels. Materials Today Communications. 2019; 21: 100701. doi: 10.1016/j.mtcomm.2019.100701

51. Michael FM, Krishnan MR, AlSoughayer S, et al. Thermo-elastic and self-healing polyacrylamide -2D nanofiller composite hydrogels for water shutoff treatment. Journal of Petroleum Science and Engineering. 2020; 193: 107391. doi: 10.1016/j.petrol.2020.107391

52. Vacanti CA. The history of tissue engineering. Journal of Cellular and Molecular Medicine. 2006; 10(3): 569-576. doi: 10.1111/j.1582-4934.2006.tb00421.x

53. Chapekar MS. Tissue engineering: challenges and opportunities. Journal of Biomedical Materials Research. 2000; 53: 617-620. doi: 10.1002/1097-4636(2000)53:6<617::AID-JBM1>3.0.CO;2-C

54. Atala A, Lanza R. Methods of Tissue Engineering. Gulf Professional Publishing; 2001.

55. Stock UA, Vacanti JP. Tissue Engineering: Current State and Prospects. Annual Review of Medicine. 2001; 52(1): 443-451. doi: 10.1146/annurev.med.52.1.443

56. Black CRM, Goriainov V, Gibbs D, et al. Bone Tissue Engineering. Current Molecular Biology Reports. 2015; 1(3): 132-140. doi: 10.1007/s40610-015-0022-2

57. Shafiee A, Atala A. Tissue Engineering: Toward a New Era of Medicine. Annual Review of Medicine. 2017; 68(1): 29-40. doi: 10.1146/annurev-med-102715-092331

58. Patrick CW, Mikos AG, McIntire LV. Prospectus of Tissue Engineering. In: Patrick CW, Mikos AG, McIntire LV, Langer RS (editors). Frontiers in Tissue Engineering, 1st ed. Pergamon; 1998. pp. 3-11. doi: 10.1016/b978-008042689-1/50003-0

59. Ikada Y. Tissue Engineering: Fundamentals and Applications. Elsevier; 2011.

60. Abdelaziz AG, Nageh H, Abdo SM, et al. A Review of 3D Polymeric Scaffolds for Bone Tissue Engineering: Principles, Fabrication Techniques, Immunomodulatory Roles, and Challenges. Bioengineering. 2023; 10(2): 204. doi: 10.3390/bioengineering10020204

61. Hutmacher DW. Scaffolds in tissue engineering bone and cartilage. Biomaterials. 2000; 21: 2529-2543. doi: 10.1016/S0142-9612(00)00121-6

62. Guarino V, Causa F, Netti PA, et al. The role of hydroxyapatite as solid signal on performance of PCL porous scaffolds for bone tissue regeneration. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2008; 86B(2): 548-557. doi: 10.1002/jbm.b.31055

63. Gómez S, Vlad MD, López J, et al. Design and properties of 3D scaffolds for bone tissue engineering. Acta Biomaterialia. 2016; 42: 341-350. doi: 10.1016/j.actbio.2016.06.032

64. Mirkhalaf M, Men Y, Wang R, et al. Personalized 3D printed bone scaffolds: A review. Acta Biomaterialia. 2023; 156: 110-124. doi: 10.1016/j.actbio.2022.04.014

65. Wu S, Liu X, Yeung KWK, et al. Biomimetic porous scaffolds for bone tissue engineering. Materials Science and Engineering: R: Reports. 2014; 80: 1-36. doi: 10.1016/j.mser.2014.04.001

66. Qu H, Fu H, Han Z, et al. Biomaterials for bone tissue engineering scaffolds: a review. RSC Advances. 2019; 9(45): 26252-26262. doi: 10.1039/c9ra05214c

67. Lichte P, Pape HC, Pufe T, et al. Scaffolds for bone healing: Concepts, materials and evidence. Injury. 2011; 42(6): 569-573. doi: 10.1016/j.injury.2011.03.033

68. Chocholata P, Kulda V, Babuska V. Fabrication of Scaffolds for Bone-Tissue Regeneration. Materials. 2019; 12(4): 568. doi: 10.3390/ma12040568

69. Wang C, Huang W, Zhou Y, et al. 3D printing of bone tissue engineering scaffolds. Bioactive Materials. 2020; 5(1): 82-91. doi: 10.1016/j.bioactmat.2020.01.004

70. Alonzo M, Alvarez Primo F, Anil Kumar S, et al. Bone tissue engineering techniques, advances, and scaffolds for treatment of bone defects. Current Opinion in Biomedical Engineering. 2021; 17: 100248. doi: 10.1016/j.cobme.2020.100248

71. Polo-Corrales L, Latorre-Esteves M, Ramirez-Vick JE. Scaffold Design for Bone Regeneration. Journal of Nanoscience and Nanotechnology. 2014; 14(1): 15-56. doi: 10.1166/jnn.2014.9127

72. Cao S, Zhao Y, Hu Y, et al. New perspectives: In-situ tissue engineering for bone repair scaffold. Composites Part B: Engineering. 2020; 202: 108445. doi: 10.1016/j.compositesb.2020.108445

73. Collins MN, Ren G, Young K, et al. Scaffold Fabrication Technologies and Structure/Function Properties in Bone Tissue Engineering. Advanced Functional Materials. 2021; 31(21). doi: 10.1002/adfm.202010609

74. Roseti L, Parisi V, Petretta M, et al. Scaffolds for Bone Tissue Engineering: State of the art and new perspectives. Materials Science and Engineering: C. 2017; 78: 1246-1262. doi: 10.1016/j.msec.2017.05.017

75. Thadavirul N, Pavasant P, Supaphol P. Development of polycaprolactone porous scaffolds by combining solvent casting, particulate leaching, and polymer leaching techniques for bone tissue engineering. Journal of Biomedical Materials Research Part A. 2013; 102(10): 3379-3392. doi: 10.1002/jbm.a.35010

76. Sola A, Bertacchini J, D’Avella D, et al. Development of solvent-casting particulate leaching (SCPL) polymer scaffolds as improved three-dimensional supports to mimic the bone marrow niche. Materials Science and Engineering: C. 2019; 96: 153-165. doi: 10.1016/j.msec.2018.10.086

77. Prasad A, Sankar MR, Katiyar V. State of Art on Solvent Casting Particulate Leaching Method for Orthopedic ScaffoldsFabrication. Materials Today: Proceedings. 2017; 4(2): 898-907. doi: 10.1016/j.matpr.2017.01.101

78. Koyyada A, Orsu P. Recent Advancements and Associated Challenges of Scaffold Fabrication Techniques in Tissue Engineering Applications. Regenerative Engineering and Translational Medicine. 2020; 7(2): 147-159. doi: 10.1007/s40883-020-00166-y

79. Zhang Z, Feng Y, Wang L, et al. A review of preparation methods of porous skin tissue engineering scaffolds. Materials Today Communications. 2022; 32: 104109. doi: 10.1016/j.mtcomm.2022.104109

80. Suamte L, Tirkey A, Barman J, et al. Various manufacturing methods and ideal properties of scaffolds for tissue engineering applications. Smart Materials in Manufacturing. 2023; 1: 100011. doi: 10.1016/j.smmf.2022.100011

81. Fereshteh Z. Freeze-drying technologies for 3D scaffold engineering. In: Deng Y, Kuipe J (editors). Functional 3D Tissue Engineering Scaffolds. Elsevier; 2018. pp. 151-174. doi: 10.1016/b978-0-08-100979-6.00007-0

82. Kazimierczak P, Benko A, Palka K, et al. Novel synthesis method combining a foaming agent with freeze-drying to obtain hybrid highly macroporous bone scaffolds. Journal of Materials Science & Technology. 2020; 43: 52-63. doi: 10.1016/j.jmst.2020.01.006

83. Putra DFA, Aji BB, Ningsih HS, et al. Preparation and Characterization of Freeze-Dried β-Tricalcium Phosphate/Barium Titanate/Collagen Composite Scaffolds for Bone Tissue Engineering in Orthopedic Applications. Ceramics. 2023; 6(4): 2148-2161. doi: 10.3390/ceramics6040132

84. Samitsu S, Zhang R, Peng X, et al. Flash freezing route to mesoporous polymer nanofibre networks. Nature Communications. 2013; 4(1). doi: 10.1038/ncomms3653

85. Krishnan MR, Samitsu S, Fujii Y, et al. Hydrophilic polymer nanofibre networks for rapid removal of aromatic compounds from water. Chem Commun. 2014; 50(66): 9393-9396. doi: 10.1039/c4cc01786b

86. Krishnan MR, Chien YC, Cheng CF, et al. Fabrication of Mesoporous Polystyrene Films with Controlled Porosity and Pore Size by Solvent Annealing for Templated Syntheses. Langmuir. 2017; 33(34): 8428-8435. doi: 10.1021/acs.langmuir.7b02195

87. Cheng CF, Chen YM, Zou F, et al. Li-Ion Capacitor Integrated with Nano-network-Structured Ni/NiO/C Anode and Nitrogen-Doped Carbonized Metal–Organic Framework Cathode with High Power and Long Cyclability. ACS Applied Materials & Interfaces. 2019; 11(34): 30694-30702. doi: 10.1021/acsami.9b06354

88. Chien YC, Huang LY, Yang KC, et al. Fabrication of metallic nanonetworks via templated electroless plating as hydrogenation catalyst. Emergent Materials. 2020; 4(2): 493-501. doi: 10.1007/s42247-020-00108-y

89. Lo TY, Krishnan MR, Lu KY, et al. Silicon-containing block copolymers for lithographic applications. Progress in Polymer Science. 2018; 77: 19-68. doi: 10.1016/j.progpolymsci.2017.10.002

90. Mi A, Guo L, Guo S, et al. Freeze-casting in synthetic porous materials: Principles, different dimensional building units and recent applications. Sustainable Materials and Technologies. 2024; 39: e00830. doi: 10.1016/j.susmat.2024.e00830

91. Hajihasani Biouki M, Mobedi H, Karkhaneh A, et al. Development of a simvastatin loaded injectable porous scaffold in situ formed by phase inversion method for bone tissue regeneration. The International Journal of Artificial Organs. 2018; 42(2): 72-79. doi: 10.1177/0391398818806161

92. Duarte ARC, Mano JF, Reis RL. Dexamethasone-loaded scaffolds prepared by supercritical-assisted phase inversion. Acta Biomaterialia. 2009; 5(6): 2054-2062. doi: 10.1016/j.actbio.2009.01.047

93. Duarte ARC, Mano JF, Reis RL. Supercritical phase inversion of starch-poly(ε-caprolactone) for tissue engineering applications. Journal of Materials Science: Materials in Medicine. 2009; 21(2): 533-540. doi: 10.1007/s10856-009-3909-8

94. Duarte ARC, Mano JF, Reis RL. The role of organic solvent on the preparation of chitosan scaffolds by supercritical assisted phase inversion. The Journal of Supercritical Fluids. 2012; 72: 326-332. doi: 10.1016/j.supflu.2010.12.004

95. Seyed Hakim R, Maghsoud Z, Halabian R. Fabrication and evaluation of polycaprolactone/olive oil scaffolds by phase inversion for tissue engineering. European Polymer Journal. 2021; 150: 110394. doi: 10.1016/j.eurpolymj.2021.110394

96. Duarte ARC, Mano JF, Reis RL. Supercritical fluids in biomedical and tissue engineering applications: a review. International Materials Reviews. 2009; 54(4): 214-222. doi: 10.1179/174328009x411181

97. Yang DZ, Chen AZ, Wang SB, et al. Preparation of poly(L-lactic acid) nanofiber scaffolds with a rough surface by phase inversion using supercritical carbon dioxide. Biomedical Materials. 2015; 10(3): 035015. doi: 10.1088/1748-6041/10/3/035015

98. Duarte ARC, Mano JF, Reis RL. Preparation of starch-based scaffolds for tissue engineering by supercritical immersion precipitation. The Journal of Supercritical Fluids. 2009; 49(2): 279-285. doi: 10.1016/j.supflu.2008.12.008

99. Papenburg BJ, Bolhuis-Versteeg LAM, Grijpma DW, et al. A facile method to fabricate poly(l-lactide) nano-fibrous morphologies by phase inversion. Acta Biomaterialia. 2010; 6(7): 2477-2483. doi: 10.1016/j.actbio.2009.12.051

100. Yoshimoto H, Shin Y, Terai H, Vacanti J. A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials. 2003; 24: 2077-2082. doi: 10.1016/S0142-9612(02)00635-X

101. Yu Y, Hua S, Yang M, et al. Fabrication and characterization of electrospinning/3D printing bone tissue engineering scaffold. RSC Advances. 2016; 6(112): 110557-110565. doi: 10.1039/c6ra17718b

102. Prabhakaran MP, Venugopal J, Ramakrishna S. Electrospun nanostructured scaffolds for bone tissue engineering. Acta Biomaterialia. 2009; 5(8): 2884-2893. doi: 10.1016/j.actbio.2009.05.007

103. Wang Z, Wang Y, Yan J, et al. Pharmaceutical electrospinning and 3D printing scaffold design for bone regeneration. Advanced Drug Delivery Reviews. 2021; 174: 504-534. doi: 10.1016/j.addr.2021.05.007

104. Maji K, Pramanik K. Electrospun scaffold for bone regeneration. International Journal of Polymeric Materials and Polymeric Biomaterials. 2021; 71(11): 842-857. doi: 10.1080/00914037.2021.1915784

105. Lin W, Chen M, Qu T, et al. Three‐dimensional electrospun nanofibrous scaffolds for bone tissue engineering. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2019; 108(4): 1311-1321. doi: 10.1002/jbm.b.34479

106. Qi Y, Lv H, Huang Q, et al. The Synergetic Effect of 3D Printing and Electrospinning Techniques in the Fabrication of Bone Scaffolds. Annals of Biomedical Engineering. 2024; 52(6): 1518-1533. doi: 10.1007/s10439-024-03500-5

107. Khajavi R, Abbasipour M, Bahador A. Electrospun biodegradable nanofibers scaffolds for bone tissue engineering. Journal of Applied Polymer Science. 2015; 133(3). doi: 10.1002/app.42883

108. Andric T, Wright LD, Taylor BL, et al. Fabrication and characterization of three‐dimensional electrospun scaffolds for bone tissue engineering. Journal of Biomedical Materials Research Part A. 2012; 100A(8): 2097-2105. doi: 10.1002/jbm.a.34045

109. Jang JH, Castano O, Kim HW. Electrospun materials as potential platforms for bone tissue engineering. Advanced Drug Delivery Reviews. 2009; 61(12): 1065-1083. doi: 10.1016/j.addr.2009.07.008

110. Yang C, Shao Q, Han Y, et al. Fibers by Electrospinning and Their Emerging Applications in Bone Tissue Engineering. Applied Sciences. 2021; 11(19): 9082. doi: 10.3390/app11199082

111. Bhattarai DP, Aguilar LE, Park CH, et al. A Review on Properties of Natural and Synthetic Based Electrospun Fibrous Materials for Bone Tissue Engineering. Membranes. 2018; 8(3): 62. doi: 10.3390/membranes8030062

112. Li W, Laurencin CT, Caterson EJ, et al. Electrospun nanofibrous structure: A novel scaffold for tissue engineering. Journal of Biomedical Materials Research. 2002; 60(4): 613-621. doi: 10.1002/jbm.10167

113. Sun W, Darling A, Starly B, et al. Computer‐aided tissue engineering: overview, scope and challenges. Biotechnology and Applied Biochemistry. 2004; 39(1): 29-47. doi: 10.1042/ba20030108

114. Sun W, Lal P. Recent development on computer aided tissue engineering-a review. Computer Methods and Programs in Biomedicine. 2002; 67: 85-103. doi: 10.1016/S0169-2607(01)00116-X

115. Giannitelli SM, Accoto D, Trombetta M, et al. Current trends in the design of scaffolds for computer-aided tissue engineering. Acta Biomaterialia. 2014; 10(2): 580-594. doi: 10.1016/j.actbio.2013.10.024

116. Top N, Şahin İ, Gökçe H, et al. Computer-aided design and additive manufacturing of bone scaffolds for tissue engineering: state of the art. Journal of Materials Research. 2021; 36(19): 3725-3745. doi: 10.1557/s43578-021-00156-y

117. Di Gravina GM, Loi G, Auricchio F, et al. Computer-aided engineering and additive manufacturing for bioreactors in tissue engineering: State of the art and perspectives. Biophysics Reviews. 2023; 4(3). doi: 10.1063/5.0156704

118. Zenobi E, Merco M, Mochi F, et al. Tailoring the Microarchitectures of 3D Printed Bone-like Scaffolds for Tissue Engineering Applications. Bioengineering. 2023; 10(5): 567. doi: 10.3390/bioengineering10050567

119. Bardini R, Di Carlo S. Computational Methods for Biofabrication in Tissue Engineering and Regenerative Medicine - a literature review. Computational and Structural Biotechnology Journal. 2024; 23: 601-616. doi: 10.1101/2023.03.03.530995

120. Bermejillo Barrera MD, Franco-Martínez F, Díaz Lantada A. Artificial Intelligence Aided Design of Tissue Engineering Scaffolds Employing Virtual Tomography and 3D Convolutional Neural Networks. Materials. 2021; 14(18): 5278. doi: 10.3390/ma14185278

121. Foresti R, Rossi S, Pinelli S, et al. Highly-defined bioprinting of long-term vascularized scaffolds with Bio-Trap: Complex geometry functionalization and process parameters with computer aided tissue engineering. Materialia. 2020; 9: 100560. doi: 10.1016/j.mtla.2019.100560

122. Sahai N, Gogoi M. Computer aided designing and finite element analysis for development of porous 3D tissue scaffold - a review. International Journal of Biomedical Engineering and Technology. 2020; 33(2): 174. doi: 10.1504/ijbet.2020.107712

123. Fernández MP, Witte F, Tozzi G. Applications of X‐ray computed tomography for the evaluation of biomaterial‐mediated bone regeneration in critical‐sized defects. Journal of Microscopy. 2019; 277(3): 179-196. doi: 10.1111/jmi.12844

124. Noroozi R, Tatar F, Zolfagharian A, et al. Additively Manufactured Multi-Morphology Bone-like Porous Scaffolds: Experiments and Micro-Computed Tomography-Based Finite Element Modeling Approaches. International Journal of Bioprinting. 2022; 8(3): 556. doi: 10.18063/ijb.v8i3.556

125. Liu Y, Xie D, Zhou R, et al. 3D X-ray micro-computed tomography imaging for the microarchitecture evaluation of porous metallic implants and scaffolds. Micron. 2021; 142: 102994. doi: 10.1016/j.micron.2020.102994

126. Dixit K, Gupta P, Kamle S, et al. Structural analysis of porous bioactive glass scaffolds using micro-computed tomographic images. Journal of Materials Science. 2020; 55(27): 12705-12724. doi: 10.1007/s10853-020-04850-w

127. Rawson SD, Maksimcuka J, Withers PJ, et al. X-ray computed tomography in life sciences. BMC Biology. 2020; 18(1). doi: 10.1186/s12915-020-0753-2

128. Olăreț E, Stancu IC, Iovu H, et al. Computed Tomography as a Characterization Tool for Engineered Scaffolds with Biomedical Applications. Materials. 2021; 14(22): 6763. doi: 10.3390/ma14226763

129. Farina E, Gastaldi D, Baino F, et al. Micro computed tomography based finite element models for elastic and strength properties of 3D printed glass scaffolds. Acta Mechanica Sinica. 2021; 37(2): 292-306. doi: 10.1007/s10409-021-01065-3

130. Verykokou S, Ioannidis C, Soile S, et al. The Role of Cone Beam Computed Tomography in Periodontology: From 3D Models of Periodontal Defects to 3D-Printed Scaffolds. Journal of Personalized Medicine. 2024; 14(2): 207. doi: 10.3390/jpm14020207

131. Vanlenthe G, Hagenmuller H, Bohner M, et al. Nondestructive micro-computed tomography for biological imaging and quantification of scaffold–bone interaction in vivo. Biomaterials. 2007; 28(15): 2479-2490. doi: 10.1016/j.biomaterials.2007.01.017

132. Yang A, Wang Y, Feng Q, et al. Integrating Fluorescence and Magnetic Resonance Imaging in Biocompatible Scaffold for Real‐Time Bone Repair Monitoring and Assessment. Advanced Healthcare Materials. 2023; 13(6). doi: 10.1002/adhm.202302687

133. Washburn NR, Weir M, Anderson P, et al. Bone formation in polymeric scaffolds evaluated by proton magnetic resonance microscopy and X‐ray microtomography. Journal of Biomedical Materials Research Part A. 2004; 69A(4): 738-747. doi: 10.1002/jbm.a.30054

134. Zhao M, Li X, Fu F, et al. Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering. Neural Regeneration Research. 2017; 12(4): 614. doi: 10.4103/1673-5374.205101

135. van der Zande M, Sitharaman B, Walboomers XF, et al. In Vivo Magnetic Resonance Imaging of the Distribution Pattern of Gadonanotubes Released from a Degrading Poly(Lactic-Co-Glycolic Acid) Scaffold. Tissue Engineering Part C: Methods. 2011; 17(1): 19-26. doi: 10.1089/ten.tec.2010.0089

136. Sajesh KM, Ashokan A, Gowd GS, et al. Magnetic 3D scaffold: A theranostic tool for tissue regeneration and non-invasive imaging in vivo. Nanomedicine: Nanotechnology, Biology and Medicine. 2019; 18: 179-188. doi: 10.1016/j.nano.2019.02.022

137. Huang J, Lv Z, Wang Y, et al. In Vivo MRI and X‐Ray Bifunctional Imaging of Polymeric Composite Supplemented with GdPO4·H2O Nanobundles for Tracing Bone Implant and Bone Regeneration. Advanced Healthcare Materials. 2016; 5(17): 2182-2190. doi: 10.1002/adhm.201600249

138. Stuckey DJ, Ishii H, Chen QZ, et al. Magnetic Resonance Imaging Evaluation of Remodeling by Cardiac Elastomeric Tissue Scaffold Biomaterials in a Rat Model of Myocardial Infarction. Tissue Engineering Part A. 2010; 16(11): 3395-3402. doi: 10.1089/ten.tea.2010.0213

139. Chesnick IE, Fowler CB, Mason JT, et al. Novel mineral contrast agent for magnetic resonance studies of bone implants grown on a chick chorioallantoic membrane. Magnetic Resonance Imaging. 2011; 29(9): 1244-1254. doi: 10.1016/j.mri.2011.07.022

140. Heljak MK, Kurzydlowski KJ, Swieszkowski W. Computer aided design of architecture of degradable tissue engineering scaffolds. Computer Methods in Biomechanics and Biomedical Engineering. 2017; 20(15): 1623-1632. doi: 10.1080/10255842.2017.1399263

141. Lacroix D, Planell JA, Prendergast PJ. Computer-aided design and finite-element modelling of biomaterial scaffolds for bone tissue engineering. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. 2009; 367(1895): 1993-2009. doi: 10.1098/rsta.2009.0024

142. Fang Z, Starly B, Sun W. Computer-aided characterization for effective mechanical properties of porous tissue scaffolds. Computer-Aided Design. 2005; 37(1): 65-72. doi: 10.1016/j.cad.2004.04.002

143. Sun W, Starly B, Darling A, et al. Computer‐aided tissue engineering: application to biomimetic modelling and design of tissue scaffolds. Biotechnology and Applied Biochemistry. 2004; 39(1): 49-58. doi: 10.1042/ba20030109

144. Ramin E, Harris RA. Advanced computer-aided design for bone tissue-engineering scaffolds. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine. 2009; 223(3): 289-301. doi: 10.1243/09544119jeim452

145. Sahai N, Saxena KK, Gogoi M. Modelling and simulation for fabrication of 3D printed polymeric porous tissue scaffolds. Advances in Materials and Processing Technologies. 2020; 6(3): 530-539. doi: 10.1080/2374068x.2020.1728643

146. Naing MW, Chua CK, Leong KF, et al. Fabrication of customised scaffolds using computer‐aided design and rapid prototyping techniques. Rapid Prototyping Journal. 2005; 11(4): 249-259. doi: 10.1108/13552540510612938

147. Quadrani P, Pasini A, Mattioli-Belmonte M, et al. High-resolution 3D scaffold model for engineered tissue fabrication using a rapid prototyping technique. Medical & Biological Engineering & Computing. 2005; 43(2): 196-199. doi: 10.1007/bf02345954

148. Chua CK, Leong KF, An J. Introduction to rapid prototyping of biomaterials. Rapid Prototyping of Biomaterials. Published online 2020: 1-15. doi: 10.1016/b978-0-08-102663-2.00001-0

149. Sing SL, Tey CF, Tan JHK, et al. 3D printing of metals in rapid prototyping of biomaterials: Techniques in additive manufacturing. In: Rapid Prototyping of Biomaterials. Elsevier. 2020: 17-40. doi: 10.1016/b978-0-08-102663-2.00002-2

150. Ansari AI, Sheikh NA. Bone Tissue Regeneration: Rapid Prototyping Technology in Scaffold Design. Journal of The Institution of Engineers (India): Series C. 2022; 103(5): 1303-1324. doi: 10.1007/s40032-022-00872-2

151. Sun F, Wang T, Yang Y. Hydroxyapatite composite scaffold for bone regeneration via rapid prototyping technique: a review. Rapid Prototyping Journal. 2021; 28(3): 585-605. doi: 10.1108/rpj-09-2020-0224

152. Sharma P, Joshi D, Dhanopia A, et al. A review of rapid prototyping and its applications. SKIT Research Journal. 2020; 10(1): 89. doi: 10.47904/ijskit.10.1.2020.89-97

153. Leong K, Cheah C, Chua C. Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials. 2003; 24: 2363-2378. doi: 10.1016/S0142-9612(03)00030-9