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Current Advances in Hydroxyapatite- and β-Tricalcium Phosphate-Based Composites for Biomedical Applications: A Review

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Abstract

This review focuses on the advances made in the synthesis and application of hydroxyapatite (HA)- and β-tricalcium phosphate (β-TCP)-based composites for biomedical purposes, with focuses placed on both laboratory exploration and clinical translation. First, polymeric matrix materials are reviewed, with comparisons between naturally- and synthetically-derived polymers briefly introduced. Second, calcium phosphates used in hard tissue replacement are broadly reviewed, with primary distinctions between HA and β-TCP discussed. A wide range of HA- and β-TCP-polymer composites for various applications are then reviewed extensively, with both biological and mechanical properties emphasized, along with the various fabrication methods that have been developed. Finally, clinically implemented composites are surveyed, with commercially available products and their respective uses highlighted.

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References

  1. A. Ho-Shui-Ling et al., Bone regeneration strategies: engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials (2018). https://doi.org/10.1016/j.biomaterials.2018.07.017

    Article  Google Scholar 

  2. G. Rh-Owen, M. Dard, H. Larjava, Hydoxyapatite/beta-tricalcium phosphate biphasic ceramics as regenerative material for the repair of complex bone defects. J. Biomed. Mater. Res. B Appl. Biomater. (2018). https://doi.org/10.1002/jbm.b.34049

    Article  Google Scholar 

  3. M. Dziadek, E. Stodolak-Zych, K. Cholewa-Kowalska, Biodegradable ceramic–polymer composites for biomedical applications: a review. Mater. Sci. Eng. C Mater. Biol. Appl. (2017). https://doi.org/10.1016/j.msec.2016.10.014

    Article  Google Scholar 

  4. T. Miyazaki, M. Kawashita, C. Ohtsuki, Ceramic–polymer composites for biomedical applications, in Handbook of Bioceramics and Biocomposites. ed. by I.V. Antoniac (Springer, Cham, 2016), pp.287–300

    Chapter  Google Scholar 

  5. L.C. Gerhardt, A.R. Boccaccini, Bioactive glass and glass-ceramic scaffolds for bone tissue engineering. Materials (Basel) (2010). https://doi.org/10.3390/ma3073867

    Article  Google Scholar 

  6. G. Fernandez de Grado et al., Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management. J. Tissue Eng. (2018). https://doi.org/10.1177/2041731418776819

    Article  Google Scholar 

  7. V.S. Kattimani, S. Kondaka, K.P. Lingamaneni, Hydroxyapatite–-past, present, and future in bone regeneration. Bone Tissue Regen. Insights (2016). https://doi.org/10.4137/BTRI.S36138

    Article  Google Scholar 

  8. H.-M. Ng et al., Hydroxyapatite for poly(α-hydroxy esters) biocomposites applications. Polym. Rev. (2019). https://doi.org/10.1080/15583724.2018.1488729

    Article  Google Scholar 

  9. I. Sallent et al., The few who made it: commercially and clinically successful innovative bone grafts. Front. Bioeng. Biotechnol. (2020). https://doi.org/10.3389/fbioe.2020.00952

    Article  Google Scholar 

  10. H.T. Aiyelabegan, E. Sadroddiny, Fundamentals of protein and cell interactions in biomaterials. Biomed. Pharmacother. (2017). https://doi.org/10.1016/j.biopha.2017.01.136

    Article  Google Scholar 

  11. R. Jimbo et al., Protein adsorption to surface chemistry and crystal structure modification of titanium surfaces. J. Oral Maxillofac. Res. (2010). https://doi.org/10.5037/jomr.2010.1303

    Article  Google Scholar 

  12. I. Antoniac, Handbook of Bioceramics and Biocomposites (Springer, Cham, 2016)

    Book  Google Scholar 

  13. E. Fiume et al., Hydroxyapatite for biomedical applications: a short overview. Ceramics (2021). https://doi.org/10.3390/ceramics4040039

    Article  Google Scholar 

  14. A. Szczes, L. Holysz, E. Chibowski, Synthesis of hydroxyapatite for biomedical applications. Adv. Colloid Interface Sci. (2017). https://doi.org/10.1016/j.cis.2017.04.007

    Article  Google Scholar 

  15. N. Vandecandelaere, C. Rey, C. Drouet, Biomimetic apatite-based biomaterials: on the critical impact of synthesis and post-synthesis parameters. J. Mater. Sci. Mater. Med. (2012). https://doi.org/10.1007/s10856-012-4719-y

    Article  Google Scholar 

  16. A. Ressler et al., Ionic substituted hydroxyapatite for bone regeneration applications: a review. Open Ceram. (2021). https://doi.org/10.1016/j.oceram.2021.100122

    Article  Google Scholar 

  17. M. Šupová, Substituted hydroxyapatites for biomedical applications: a review. Ceram. Int. (2015). https://doi.org/10.1016/j.ceramint.2015.03.316

    Article  Google Scholar 

  18. Y. Jiang, Z. Yuan, J. Huang, Substituted hydroxyapatite: a recent development. Mater. Technol. (2020). https://doi.org/10.1080/10667857.2019.1664096

    Article  Google Scholar 

  19. M. Bohner, B.L.G. Santoni, N. Döbelin, β-Tricalcium phosphate for bone substitution: synthesis and properties. Acta Biomater. (2020). https://doi.org/10.1016/j.actbio.2020.06.022

    Article  Google Scholar 

  20. E.B. Nery, K.L. Lynch, G.E. Rooney, Alveolar ridge augmentation with tricalcium phosphate ceramic. J. Prosthet. Dent. (1978). https://doi.org/10.1016/0022-3913(78)90067-7

    Article  Google Scholar 

  21. S.C. Roberts Jr., J.D. Brilliant, Tricalcium phosphate as an adjunct to apical closure in pulpless permanent teeth. J. Endod. (1975). https://doi.org/10.1016/s0099-2399(75)80038-0

    Article  Google Scholar 

  22. H. Cao, N. Kuboyama, A biodegradable porous composite scaffold of PGA/beta-TCP for bone tissue engineering. Bone (2010). https://doi.org/10.1016/j.bone.2009.09.031

    Article  Google Scholar 

  23. E.R. Ratner et al., Biomaterials Science: An Introduction to Materials in Medicine (Elsevier, Amsterdam, 2013)

    Google Scholar 

  24. M.B. Murphy, A.G. Mikos, Polymer scaffold fabrication, in Principles of Tissue Engineering, 3rd edn., ed. by R. Lanza, R. Langer, J. Vacanti (Academic Press, Burlington, 2007), pp.309–321

    Chapter  Google Scholar 

  25. M. Alizadeh-Osgouei, Y. Li, C. Wen, A comprehensive review of biodegradable synthetic polymer–ceramic composites and their manufacture for biomedical applications. Bioact. Mater. (2019). https://doi.org/10.1016/j.bioactmat.2018.11.003

    Article  Google Scholar 

  26. D. Chuan et al., Stereocomplex poly(lactic acid)-based composite nanofiber membranes with highly dispersed hydroxyapatite for potential bone tissue engineering. Compos. Sci. Technol. (2020). https://doi.org/10.1016/j.compscitech.2020.108107

    Article  Google Scholar 

  27. J.O. Akindoyo et al., Impact modified PLA-hydroxyapatite composites—thermo-mechanical properties. Composites A Appl. Sci. Manuf. (2018). https://doi.org/10.1016/j.compositesa.2018.01.017

    Article  Google Scholar 

  28. J. Wei et al., 3D-printed hydroxyapatite microspheres reinforced PLGA scaffolds for bone regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. (2021). https://doi.org/10.1016/j.msec.2021.112618

    Article  Google Scholar 

  29. R. Ma, D. Guo, Evaluating the bioactivity of a hydroxyapatite-incorporated polyetheretherketone biocomposite. J. Orthop. Surg. Res. (2019). https://doi.org/10.1186/s13018-019-1069-1

    Article  Google Scholar 

  30. A. Zima, Hydroxyapatite-chitosan based bioactive hybrid biomaterials with improved mechanical strength. Spectrochim. Acta A Mol. Biomol. Spectrosc. (2018). https://doi.org/10.1016/j.saa.2017.12.008

    Article  Google Scholar 

  31. H. Zhao, H. Jin, J. Cai, Preparation and characterization of nano-hydroxyapatite/chitosan composite with enhanced compressive strength by urease-catalyzed method. Mater. Lett. (2014). https://doi.org/10.1016/j.matlet.2013.05.082

    Article  Google Scholar 

  32. K.K. Gómez-Lizárraga et al., Polycaprolactone- and polycaprolactone/ceramic-based 3D-bioplotted porous scaffolds for bone regeneration: a comparative study. Mater. Sci. Eng. C Mater. Biol. Appl. (2017). https://doi.org/10.1016/j.msec.2017.05.003

    Article  Google Scholar 

  33. X. Jing, H.Y. Mi, L.S. Turng, Comparison between PCL/hydroxyapatite (HA) and PCL/halloysite nanotube (HNT) composite scaffolds prepared by co-extrusion and gas foaming. Mater. Sci. Eng. C Mater. Biol. Appl. (2017). https://doi.org/10.1016/j.msec.2016.11.049

    Article  Google Scholar 

  34. S. Minardi et al., Biomimetic hydroxyapatite/collagen composite drives bone niche recapitulation in a rabbit orthotopic model. Mater. Today (2019). https://doi.org/10.1016/j.mtbio.2019.100005

    Article  Google Scholar 

  35. T. Yeo et al., Promoting bone regeneration by 3D-printed poly(glycolic acid)/hydroxyapatite composite scaffolds. J. Ind. Eng. Chem. (2021). https://doi.org/10.1016/j.jiec.2020.11.004

    Article  Google Scholar 

  36. L.F. Sukhodub et al., Synthesis and characterization of hydroxyapatite-alginate nanostructured composites for the controlled drug release. Mater. Chem. Phys. (2018). https://doi.org/10.1016/j.matchemphys.2018.06.071

    Article  Google Scholar 

  37. Y.G. Bi, Z.T. Lin, S.T. Deng, Fabrication and characterization of hydroxyapatite/sodium alginate/chitosan composite microspheres for drug delivery and bone tissue engineering. Mater. Sci. Eng. C Mater. Biol. Appl. (2019). https://doi.org/10.1016/j.msec.2019.03.040

    Article  Google Scholar 

  38. R. Ramirez-Agudelo et al., Hybrid nanofibers based on poly-caprolactone/gelatin/hydroxyapatite nanoparticles-loaded doxycycline: effective anti-tumoral and antibacterial activity. Mater. Sci. Eng. C Mater. Biol. Appl. (2018). https://doi.org/10.1016/j.msec.2017.08.012

    Article  Google Scholar 

  39. M. Stevanović et al., Gentamicin-loaded bioactive hydroxyapatite/chitosan composite coating electrodeposited on titanium. ACS Biomater. Sci. Eng. (2018). https://doi.org/10.1021/acsbiomaterials.8b00859

    Article  Google Scholar 

  40. F. Manzoor et al., 3D printed PEEK/HA composites for bone tissue engineering applications: effect of material formulation on mechanical performance and bioactive potential. J. Mech. Behav. Biomed. Mater. (2021). https://doi.org/10.1016/j.jmbbm.2021.104601

    Article  Google Scholar 

  41. F.E. Bastan et al., Electrophoretic co-deposition of PEEK-hydroxyapatite composite coatings for biomedical applications. Colloids Surf. B Biointerfaces (2018). https://doi.org/10.1016/j.colsurfb.2018.05.005

    Article  Google Scholar 

  42. J.Z. Xu et al., Bone-like polymeric composites with a combination of bioactive glass and hydroxyapatite: simultaneous enhancement of mechanical performance and bioactivity. ACS Biomater. Sci. Eng. (2018). https://doi.org/10.1021/acsbiomaterials.8b01174

    Article  Google Scholar 

  43. I.L. Ardelean et al., Collagen/hydroxyapatite bone grafts manufactured by homogeneous/heterogeneous 3D printing. Mater. Lett. (2018). https://doi.org/10.1016/j.matlet.2018.08.042

    Article  Google Scholar 

  44. S.L. McNamara et al., Rheological characterization, compression, and injection molding of hydroxyapatite-silk fibroin composites. Biomaterials (2021). https://doi.org/10.1016/j.biomaterials.2020.120643

    Article  Google Scholar 

  45. Y.K. Yeon et al., New concept of 3D printed bone clip (polylactic acid/hydroxyapatite/silk composite) for internal fixation of bone fractures. J. Biomater. Sci. Polym. (2018). https://doi.org/10.1080/09205063.2017.1384199

    Article  Google Scholar 

  46. J.-W. Kim et al., Effect of morphological characteristics and biomineralization of 3D-printed gelatin/hyaluronic acid/hydroxyapatite composite scaffolds on bone tissue regeneration. Int. J. Mol. Sci. (2021). https://doi.org/10.3390/ijms22136794

    Article  Google Scholar 

  47. Q. Wang et al., 3D printed PCL/β-TCP cross-scale scaffold with high-precision fiber for providing cell growth and forming bones in the pores. Mater. Sci. Eng. C (2021). https://doi.org/10.1016/j.msec.2021.112197

    Article  Google Scholar 

  48. C. Beatrice et al., Engineering printable composites of poly(ε-polycaprolactone)/β-tricalcium phosphate for biomedical applications. Polym. Compos. (2020). https://doi.org/10.1002/pc.25893

    Article  Google Scholar 

  49. Y. Lai et al., Osteogenic magnesium incorporated into PLGA/TCP porous scaffold by 3D printing for repairing challenging bone defect. Biomaterials (2019). https://doi.org/10.1016/j.biomaterials.2019.01.013

    Article  Google Scholar 

  50. A. Kumar et al., Load-bearing biodegradable PCL-PGA-beta TCP scaffolds for bone tissue regeneration. J. Biomed. Mater. Res. B Appl. Biomater. (2021). https://doi.org/10.1002/jbm.b.34691

    Article  Google Scholar 

  51. M. Taherimehr, R. Bagheri, M. Taherimehr, In-vitro evaluation of thermoplastic starch/beta-tricalcium phosphate nano-biocomposite in bone tissue engineering. Ceram. Int. (2021). https://doi.org/10.1016/j.ceramint.2021.02.111

    Article  Google Scholar 

  52. T. Bian, N. Pang, H. Xing, Preparation and antibacterial evaluation of a beta-tricalcium phosphate/collagen nanofiber biomimetic composite scaffold. Mater. Chem. Phys. (2021). https://doi.org/10.1016/j.matchemphys.2021.125059

    Article  Google Scholar 

  53. D. Algul et al., In vitro release and in vivo biocompatibility studies of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue. J. Biomater. Sci. Polym. Ed. (2016). https://doi.org/10.1080/09205063.2016.1140501

    Article  Google Scholar 

  54. M. Ezati et al., Development of a PCL/gelatin/chitosan/β-TCP electrospun composite for guided bone regeneration. Prog. Biomater. (2018). https://doi.org/10.1007/s40204-018-0098-x

    Article  Google Scholar 

  55. P. Nevado et al., Preparation and in vitro evaluation of PLA/biphasic calcium phosphate filaments used for fused deposition modelling of scaffolds. Mater. Sci. Eng. C (2020). https://doi.org/10.1016/j.msec.2020.111013

    Article  Google Scholar 

  56. A. Shavandi et al., Development and characterization of hydroxyapatite/β-TCP/chitosan composites for tissue engineering applications. Mater. Sci. Eng. C (2015). https://doi.org/10.1016/j.msec.2015.07.004

    Article  Google Scholar 

  57. W. Wang, K.W.K. Yeung, Bone grafts and biomaterials substitutes for bone defect repair: a review. Bioact. Mater. (2017). https://doi.org/10.1016/j.bioactmat.2017.05.007

    Article  Google Scholar 

  58. A.J. Pugely et al., Influence of 45S5 bioactive glass in a standard calcium phosphate collagen bone graft substitute on the posterolateral fusion of rabbit spine. Iowa Orthop. J. 37, 193–198 (2017)

    Google Scholar 

  59. R. Belluomo et al., Physico-chemical characteristics and posterolateral fusion performance of biphasic calcium phosphate with submicron needle-shaped surface topography combined with a novel polymer binder. Materials (Basel) (2022). https://doi.org/10.3390/ma15041346

    Article  Google Scholar 

  60. L.A. Van Dijk et al., MagnetOs, Vitoss, and Novabone in a multi-endpoint study of posterolateral fusion: a true fusion or not? Clin. Spine Surg. (2020). https://doi.org/10.1097/BSD.0000000000000920

    Article  Google Scholar 

  61. A.J. Berg et al., Lumbar interbody fusion rates with actifuse, i-FACTOR, and Vitoss BA synthetic bone grafts. Glob. Spine J. (2014). https://doi.org/10.1055/s-0034-1376731

    Article  Google Scholar 

  62. F. Westhauser et al., Osteogenic differentiation of mesenchymal stem cells is enhanced in a 45S5-supplemented β-TCP composite scaffold: an in-vitro comparison of Vitoss and Vitoss BA. PLoS ONE (2019). https://doi.org/10.1371/journal.pone.0212799

    Article  Google Scholar 

  63. S. Tsumiyama et al., Use of unsintered hydroxyapatite and poly-l-lactic acid composite sheets for management of orbital wall fracture. J. Craniofac. Surg. (2019). https://doi.org/10.1097/scs.0000000000005734

    Article  Google Scholar 

  64. M.A. Eskan et al., The effect of membrane exposure on lateral ridge augmentation: a case-controlled study. Int. J. Implant. Dent. (2017). https://doi.org/10.1186/s40729-017-0089-z

    Article  Google Scholar 

  65. D. D’Alessandro et al., Bovine bone matrix/poly(l-lactic-co-ε-caprolactone)/gelatin hybrid scaffold (SmartBone(®)) for maxillary sinus augmentation: a histologic study on bone regeneration. Int. J. Pharm. (2017). https://doi.org/10.1016/j.ijpharm.2016.10.036

    Article  Google Scholar 

  66. E. Facciuto et al., Three-dimensional craniofacial bone reconstruction with smartbone on demand. J. Craniofac. Surg. (2019). https://doi.org/10.1097/scs.0000000000005277

    Article  Google Scholar 

  67. N.E. Epstein, High lumbar noninstrumented fusion rates using lamina autograft and Nanoss/bone marrow aspirate. Surg. Neurol. Int. (2017). https://doi.org/10.4103/sni.sni_248_17

    Article  Google Scholar 

  68. H. Zheng et al., Effect of a β-TCP collagen composite bone substitute on healing of drilled bone voids in the distal femoral condyle of rabbits. J. Biomed. Mater. Res. B Appl. Biomater. (2014). https://doi.org/10.1002/jbm.b.33016

    Article  Google Scholar 

  69. T. Fabre et al., Pilot study of safety and performance of a mixture of calcium phosphate granules combined with cellulosic-derived gel after tunnel filling created during surgical treatment of femoral head aseptic osteonecrosis. Key Eng. Mater. (2008). https://doi.org/10.4028/www.scientific.net/KEM.361-363.1295

    Article  Google Scholar 

  70. D. Guy et al., Clinical performance of moldable bioceramics for bone regeneration in maxillofacial surgery. J. Biomimetics Biomater. Biomed. Eng. (2015). https://doi.org/10.4172/2577-0268.1000109

    Article  Google Scholar 

  71. D. Fredericks et al., Comparison of two synthetic bone graft products in a rabbit posterolateral fusion model. Iowa Orthop. J. 36, 167–173 (2016)

    Google Scholar 

  72. A.S. Kanter et al., A prospective, multi-center clinical and radiographic outcomes evaluation of ChronOS strip for lumbar spine fusion. J. Clin. Neurosci. (2016). https://doi.org/10.1016/j.jocn.2015.08.012

    Article  Google Scholar 

  73. A. Wildburger et al., Sinus floor augmentation comparing an in situ hardening biphasic calcium phosphate (Hydroxyapatite/β-Tricalcium phosphate) bone graft substitute with a particulate biphasic calcium phosphate (hydroxyapatite/β-tricalcium phosphate) bone graft substitute: an experimental study in Sheep. Tissue Eng. Part C Methods (2017). https://doi.org/10.1089/ten.TEC.2016.0549

    Article  Google Scholar 

  74. L. Canullo et al., A pilot retrospective study on the effect of bone grafting after wisdom teeth extraction. Materials (2021). https://doi.org/10.3390/ma14112844

    Article  Google Scholar 

  75. A.M. Lehr et al., Efficacy of a standalone microporous ceramic versus autograft in instrumented posterolateral spinal fusion: a multicenter, randomized, intrapatient controlled, noninferiority trial. Spine (2020). https://doi.org/10.1097/BRS.0000000000003440

    Article  Google Scholar 

  76. D. Barbieri et al., Comparison of two moldable calcium phosphate-based bone graft materials in a noninstrumented canine interspinous implantation model. Tissue Eng. Part A (2017). https://doi.org/10.1089/ten.TEA.2016.0347

    Article  Google Scholar 

  77. J.D. Smucker et al., Assessment of MASTERGRAFT® STRIP with bone marrow aspirate as a graft extender in a rabbit posterolateral fusion model. Iowa Orthop. J. 32, 61–68 (2012)

    Google Scholar 

  78. M. Janssen et al., Safety and efficacy of i-FACTORTM bone graft in anterior cervical discectomy and fusion: a prospective, randomized, controlled, multi-center, investigational device exemption study. Glob. Spine J. (2016). https://doi.org/10.1055/s-0036-1582606

    Article  Google Scholar 

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  1. Inamori School of Engineering, Alfred University, Alfred, NY, USA

    Sierra K. Kucko, Sarah M. Raeman & Timothy J. Keenan

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  1. Sierra K. Kucko
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Kucko, S.K., Raeman, S.M. & Keenan, T.J. Current Advances in Hydroxyapatite- and β-Tricalcium Phosphate-Based Composites for Biomedical Applications: A Review. Biomedical Materials & Devices 1, 49–65 (2023). https://doi.org/10.1007/s44174-022-00037-w

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