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Chitosan-Hydroxyapatite Composite Scaffolds for the Controlled Release of Therapeutic Metals Ions

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Innovative Bioceramics in Translational Medicine I

Part of the book series: Springer Series in Biomaterials Science and Engineering ((SSBSE,volume 17))

Abstract

Therapeutic ions such as calcium, magnesium or copper, play an essential role in maintaining the correct physiology of our organism. They act as cofactors of enzymes, modulating cell signaling and homeostasis through various pathways. Developing biomaterials for tissue engineering that control the concentration of these ions in vivo has been proven a successful strategy to tailor cell response and, ultimately, improve tissue regeneration. Among others, chitosan, a naturally sourced polysaccharide, and hydroxyapatite, the major component of the mineral phase of bone, showed encouraging results as ion carriers. This chapter offers an overview of the use of these two materials for the purpose. Initially, the main ions used in tissue engineering and their modes of action are listed. Then, the opportunities and challenges of chitosan and hydroxyapatite in the field are discussed: their key properties, their processing into composites and the methods to fabricate tissue engineering scaffolds.

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References

  1. Kowalczewski CJ, Saul JM (2018) Biomaterials for the delivery of growth factors and other therapeutic agents in tissue engineering approaches to bone regeneration. Front Pharmacol 9:513

    PubMed  PubMed Central  Google Scholar 

  2. Muschler GF, Nakamoto C, Griffith LG (2004) Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am 86:1541–1558

    PubMed  Google Scholar 

  3. Giacca M, Zacchigna S (2012) VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther 19:622–629

    CAS  PubMed  Google Scholar 

  4. Safiaghdam H, Nokhbatolfoghahaei H, Khojasteh A (2019) Therapeutic metallic ions in bone tissue engineering: a systematic review of the literature. Iran J Pharm Res 18:101–118

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Mouriño V, Cattalini JP, Boccaccini AR (2012) Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments. J R Soc Interface 9:401–419

    PubMed  Google Scholar 

  6. Bose S, Fielding G, Tarafder S et al (2013) Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics. Trends Biotechnol 31:594–605

    CAS  PubMed  Google Scholar 

  7. Mouriño V, Vidotto R, Cattalini JP et al (2019) Enhancing biological activity of bioactive glass scaffolds by inorganic ion delivery for bone tissue engineering. Curr Opin Biomed Eng 10:23–34

    Google Scholar 

  8. Šupová M (2015) Substituted hydroxyapatites for biomedical applications: a review. Ceram Int 41:9203–9231

    Google Scholar 

  9. Bellucci D, Braccini S, Chiellini F et al (2019) Bioactive glasses and glass-ceramics versus hydroxyapatite: comparison of angiogenic potential and biological responsiveness. J Biomed Mater Res A 107:2601–2609

    CAS  PubMed  Google Scholar 

  10. Fu Z, Cui J, Zhao B et al (2021) An overview of polyester/hydroxyapatite composites for bone tissue repairing. J Orthop Translat 28:118–130

    PubMed  PubMed Central  Google Scholar 

  11. Sultan M (2018) Hydroxyapatite/polyurethane composites as promising biomaterials. Chem Pap 72:2375–2395

    CAS  Google Scholar 

  12. Marcello E, Maqbool M, Nigmatullin R et al (2021) Antibacterial composite materials based on the combination of polyhydroxyalkanoates with selenium and strontium co-substituted hydroxyapatite for bone regeneration. Front Bioeng Biotechnol 9:647007

    Google Scholar 

  13. Pighinelli L, Kucharska M (2013) Chitosan-hydroxyapatite composites. Carbohydr Polym 93:256–262

    CAS  PubMed  Google Scholar 

  14. Wahl DA, Czernuszka JT (2006) Collagen-hydroxyapatite composites for hard tissue repair. Eur Cell Mater 11:43–56

    CAS  PubMed  Google Scholar 

  15. Guibal E (2004) Interactions of metal ions with chitosan-based sorbents: a review. Sep Purif Technol 38:43–74

    CAS  Google Scholar 

  16. Guibal E, Vincent T, Navarro R (2014) Metal ion biosorption on chitosan for the synthesis of advanced materials. J Mater Sci 49:5505–5518

    CAS  Google Scholar 

  17. Qu J, Hu Q, Shen K et al (2011) The preparation and characterization of chitosan rods modified with Fe3+ by a chelation mechanism. Carbohydr Res 346:822–827

    CAS  PubMed  Google Scholar 

  18. Taylor A (1985) Therapeutic uses of trace elements. Clin Endocrinol Metab 14:703–724

    CAS  PubMed  Google Scholar 

  19. Day RM, Boccaccini AR, Shurey S et al (2004) Assessment of polyglycolic acid mesh and bioactive glass for soft-tissue engineering scaffolds. Biomaterials 25:5857–5866

    CAS  PubMed  Google Scholar 

  20. Hench LL, Polak JM (2002) Third-generation biomedical materials. Science 295:1014–1017

    CAS  PubMed  Google Scholar 

  21. Gorustovich AA, Roether JA, Boccaccini AR (2010) Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Eng Part B Rev 16:199–207

    CAS  PubMed  Google Scholar 

  22. Glenske K, Donkiewicz P, Köwitsch A et al (2018) Applications of metals for bone regeneration. Int J Mol Sci 19:826

    PubMed Central  Google Scholar 

  23. Cossey AJ, Paterson RS (2005) Loose intra-articular body following anterior cruciate ligament reconstruction. Arthroscopy 21:348–350

    CAS  PubMed  Google Scholar 

  24. Fernandes GFS, Denny WA, Dos Santos JL (2019) Boron in drug design: recent advances in the development of new therapeutic agents. Eur J Med Chem 179:791–804

    CAS  PubMed  Google Scholar 

  25. Balasubramanian P, Büttner T, Pacheco VM et al (2018) Boron-containing bioactive glasses in bone and soft tissue engineering. J Eur Ceram Soc 38:855–869

    CAS  Google Scholar 

  26. Naseri S, Lepry WC, Nazhat SN (2017) Bioactive glasses in wound healing: hope or hype? J Mater Chem B 5:6167–6174

    CAS  PubMed  Google Scholar 

  27. Yin C, Jia X, Miron RJ et al (2018) SETD7 and its contribution to boron-induced bone regeneration in boron-mesoporous bioactive glass scaffolds. Acta Biomater 73:522–530

    CAS  PubMed  Google Scholar 

  28. Ying X, Cheng S, Wang W et al (2011) Effect of boron on osteogenic differentiation of human bone marrow stromal cells. Biol Trace Elem Res 144:306–315

    CAS  PubMed  Google Scholar 

  29. Chen X, Zhao Y, Geng S et al (2015) In vivo experimental study on bone regeneration in critical bone defects using PIB nanogels/boron-containing mesoporous bioactive glass composite scaffold. Int J Nanomedicine 10:839–846

    PubMed  PubMed Central  Google Scholar 

  30. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (1997) Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. https://doi.org/10.17226/5776

  31. Wu X, Walsh K, Hoff BL et al (2020) Mineralization of biomaterials for bone tissue engineering. Bioengineering 7:132. https://doi.org/10.3390/bioengineering7040132

    Article  CAS  PubMed Central  Google Scholar 

  32. Viti F, Landini M, Mezzelani A et al (2016) Osteogenic differentiation of msc through calcium signaling activation: transcriptomics and functional analysis. PLoS One 11:e0148173

    Google Scholar 

  33. Marie PJ (2010) The calcium-sensing receptor in bone cells: a potential therapeutic target in osteoporosis. Bone 46:571–576

    CAS  PubMed  Google Scholar 

  34. Nakamura S, Matsumoto T, Sasaki J et al (2010) Effect of calcium ion concentrations on osteogenic differentiation and hematopoietic stem cell niche-related protein expression in osteoblasts. Tissue Eng Part A 16:2467–2473

    CAS  PubMed  Google Scholar 

  35. Valerio P, Pereira MM, Goes AM et al (2009) Effects of extracellular calcium concentration on the glutamate release by bioactive glass (BG60S) preincubated osteoblasts. Biomed Mater 4:045011

    Google Scholar 

  36. Kurtuldu F, Mutlu N, Michálek M et al (2021) Cerium and gallium containing mesoporous bioactive glass nanoparticles for bone regeneration: bioactivity, biocompatibility and antibacterial activity. Mater Sci Eng C Mater Biol Appl 124:112050

    Google Scholar 

  37. Qi M, Li W, Zheng X et al (2020) Cerium and its oxidant-based nanomaterials for antibacterial applications: a state-of-the-art review. Front Mater 7:213. https://doi.org/10.3389/fmats.2020.00213

    Article  Google Scholar 

  38. Battaglia V, Compagnone A, Bandino A et al (2009) Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures. Int J Biochem Cell Biol 41:586–594

    CAS  PubMed  Google Scholar 

  39. Czarnek K, Terpiłowska S, Siwicki AK (2015) Selected aspects of the action of cobalt ions in the human body. Cent Eur J Immunol 40:236–242

    PubMed  PubMed Central  Google Scholar 

  40. de Laia AGS, Barrioni BR, Valverde TM et al (2020) Therapeutic cobalt ion incorporated in poly(vinyl alcohol)/bioactive glass scaffolds for tissue engineering. J Mater Sci 55:8710–8727

    Google Scholar 

  41. Chang EL, Simmers C, Knight DA (2010) Cobalt complexes as antiviral and antibacterial agents. Pharmaceuticals 3:1711–1728

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Hong R, Kang TY, Michels CA et al (2012) Membrane lipid peroxidation in copper alloy-mediated contact killing of Escherichia coli. Appl Environ Microbiol 78:1776–1784

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Thurman RB, Gerba CP, Bitton G (1989) The molecular mechanisms of copper and silver ion disinfection of bacteria and viruses. Crit Rev Environ Control 18:295–315

    Google Scholar 

  44. Samuni A, Aronovitch J, Godinger D et al (1983) On the cytotoxicity of vitamin C and metal ions. A site-specific Fenton mechanism. Eur J Biochem 137:119–124

    CAS  PubMed  Google Scholar 

  45. Hans M, Mathews S, Mücklich F et al (2015) Physicochemical properties of copper important for its antibacterial activity and development of a unified model. Biointerphases 11:018902

    Google Scholar 

  46. dos Santos NV, Matias AC, Higa GS et al (2015) Copper uptake in mammary epithelial cells activates cyclins and triggers antioxidant response. Oxid Med Cell Longev 2015:162876. https://doi.org/10.1155/2015/162876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mansoorianfar M, Mansourianfar M, Fathi M et al (2020) Surface modification of orthopedic implants by optimized fluorine-substituted hydroxyapatite coating: enhancing corrosion behavior and cell function. Ceram Int 46:2139–2146

    CAS  Google Scholar 

  48. Ali W, Mehboob A, Han M.G. et al (2019) Effect of fluoride coating on degradation behaviour of unidirectional Mg/PLA biodegradable composite for load-bearing bone implant application. Compos Part A Appl Sci Manuf 124:105464

    Google Scholar 

  49. Borkowski L, Przekora A, Belcarz A et al (2020) Fluorapatite ceramics for bone tissue regeneration: synthesis, characterization and assessment of biomedical potential. Mater Sci Eng C Mater Biol Appl 116:111211

    Google Scholar 

  50. Amaechi BT, AbdulAzees PA, Alshareif DO et al (2019) Comparative efficacy of a hydroxyapatite and a fluoride toothpaste for prevention and remineralization of dental caries in children. BDJ Open 5:18

    PubMed  PubMed Central  Google Scholar 

  51. Al-Eesa NA, Johal A, Hill RG et al (2018) Fluoride containing bioactive glass composite for orthodontic adhesives—apatite formation properties. Dent Mater 34:1127–1133

    CAS  PubMed  Google Scholar 

  52. Berglundh T, Abrahamsson I, Albouy JP et al (2007) Bone healing at implants with a fluoride-modified surface: an experimental study in dogs. Clin Oral Implants Res 18:147–152

    CAS  PubMed  Google Scholar 

  53. Kanduti D, Sterbenk P, Artnik B (2016) Fluoride: a review of use and effects on health. Mater Sociomed 28:133–137

    PubMed  PubMed Central  Google Scholar 

  54. Liao Y, Brandt BW, Li J et al (2017) Fluoride resistance in Streptococcus mutans: a mini review. J Oral Microbiol 9:1344509

    PubMed  PubMed Central  Google Scholar 

  55. Bernstein LR (1998) Mechanisms of therapeutic activity for gallium. Pharmacol Rev 50:665–682

    CAS  PubMed  Google Scholar 

  56. Verron E, Masson M, Khoshniat S et al (2010) Gallium modulates osteoclastic bone resorption in vitro without affecting osteoblasts. Br J Pharmacol 159:1681–1692

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Verron E, Loubat A, Carle GF et al (2012) Molecular effects of gallium on osteoclastic differentiation of mouse and human monocytes. Biochem Pharmacol 83:671–679

    CAS  PubMed  Google Scholar 

  58. Łapa A, Cresswell M, Campbell I et al (2020) Gallium- and cerium-doped phosphate glasses with antibacterial properties for medical applications. Adv Eng Mater 22:1901577

    Google Scholar 

  59. Valappil SP, Ready D, Abou Neel EA et al (2009) Controlled delivery of antimicrobial gallium ions from phosphate-based glasses. Acta Biomater 5:1198–1210

    CAS  PubMed  Google Scholar 

  60. Mouriño V, Newby P, Boccaccini AR (2010) Preparation and characterization of gallium releasing 3-D alginate coated 45S5 Bioglass® based scaffolds for bone tissue engineering. Adv Eng Mater 12:B283–B291

    Google Scholar 

  61. Minandri F, Bonchi C, Frangipani E et al (2014) Promises and failures of gallium as an antibacterial agent. Future Microbiol 9:379–397

    CAS  PubMed  Google Scholar 

  62. Gloria A, Russo T, D’Amora U et al (2013) Magnetic poly(ε-caprolactone)/iron-doped hydroxyapatite nanocomposite substrates for advanced bone tissue engineering. J R Soc Interface 10:20120833

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Le NT, Richardson DR (2002) The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta 1603:31–46

    CAS  PubMed  Google Scholar 

  64. Ahmed I, Collins CA, Lewis MP et al (2004) Processing, characterisation and biocompatibility of iron-phosphate glass fibres for tissue engineering. Biomaterials 25:3223–3232

    CAS  PubMed  Google Scholar 

  65. Wong SK, Chin KY, Ima-Nirwana S (2020) The skeletal-protecting action and mechanisms of action for mood-stabilizing drug lithium chloride: current evidence and future potential research areas. Front Pharmacol 11:430

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Eren I, Yildiz M, Çivi I (2006) The effects of lithium treatment on bone mineral density in bipolar patients. Neurol Psychiatry Brain Res 13:174–179

    Google Scholar 

  67. Yuan Y, Yuan Q, Wu C et al (2019) Enhanced osteoconductivity and osseointegration in calcium polyphosphate bioceramic scaffold via lithium doping for bone regeneration. ACS Biomater Sci Eng 5:5872–5880

    CAS  PubMed  Google Scholar 

  68. Hu Y, Chen L, Gao Y et al (2020) A lithium-containing biomaterial promotes chondrogenic differentiation of induced pluripotent stem cells with reducing hypertrophy. Stem Cell Res Ther 11:77

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Liu L, Liu Y, Feng C et al (2019) Lithium-containing biomaterials stimulate bone marrow stromal cell-derived exosomal miR-130a secretion to promote angiogenesis. Biomaterials 192:523–536

    CAS  PubMed  Google Scholar 

  70. Zhou D, Qi C, Chen YX et al (2017) Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects. Int J Nanomedicine 12:2673–2687

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Malladi L, Mahapatro A, Gomes AS (2018) Fabrication of magnesium-based metallic scaffolds for bone tissue engineering. Mater Technol 33:173–182

    CAS  Google Scholar 

  72. Adhikari U, Rijal NP, Khanal S et al (2016) Magnesium incorporated chitosan based scaffolds for tissue engineering applications. Bioact Mater 1:132–139

    PubMed  PubMed Central  Google Scholar 

  73. Suryavanshi A, Khanna K, Sindhu KR et al (2017) Magnesium oxide nanoparticle-loaded polycaprolactone composite electrospun fiber scaffolds for bone-soft tissue engineering applications: in-vitro and in-vivo evaluation. Biomed Mater 12:055011

    Google Scholar 

  74. Ran J, Jiang P, Sun G et al (2017) Comparisons among Mg, Zn, Sr, and Si doped nano-hydroxyapatite/chitosan composites for load-bearing bone tissue engineering applications. Mater Chem Front 1:900–910

    CAS  Google Scholar 

  75. Diba M, Tapia F, Boccaccini AR et al (2012) Magnesium-containing bioactive glasses for biomedical applications. Int J Appl Glass Sci 3:221–253

    CAS  Google Scholar 

  76. Gu Y, Zhang J, Zhang X et al (2019) Three-dimensional printed Mg-doped β-TCP bone tissue engineering scaffolds: effects of magnesium ion concentration on osteogenesis and angiogenesis in vitro. Tissue Eng Regen Med 16:415–429

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Venkatraman SK, Swamiappan S (2020) Review on calcium- and magnesium-based silicates for bone tissue engineering applications. J Biomed Mater Res A 108:1546–1562

    CAS  PubMed  Google Scholar 

  78. Wang Y, Geng Z, Huang Y et al (2018) Unraveling the osteogenesis of magnesium by the activity of osteoblasts in vitro. J Mater Chem B 6:6615–6621

    CAS  PubMed  Google Scholar 

  79. Mammoli F, Castiglioni S, Parenti S et al (2019) Magnesium is a key regulator of the balance between osteoclast and osteoblast differentiation in the presence of vitamin D3. Int J Mol Sci 20:385

    PubMed Central  Google Scholar 

  80. Kang JI, Son MK, Choe HC et al (2016) Bone-like apatite formation on manganese-hydroxyapatite coating formed on Ti-6Al-4V alloy by plasma electrolytic oxidation. Thin Solid Films 620:126–131

    CAS  Google Scholar 

  81. Azizi F, Heidari F, Fahimipour F et al (2020) Evaluation of mechanical and biocompatibility properties of hydroxyapatite/manganese dioxide nanocomposite scaffolds for bone tissue engineering application. Int J Appl Ceram Technol 17:2439–2449

    CAS  Google Scholar 

  82. Avila DS, Puntel RL, Aschner M (2013) Manganese in health and disease. Met Ions Life Sci 13:199–227

    PubMed  PubMed Central  Google Scholar 

  83. Clegg MS, Donovan SM, Monaco MH et al (1998) The influence of manganese deficiency on serum IGF-1 and IGF binding proteins in the male rat. Proc Soc Exp Biol Med 219:41–47

    CAS  PubMed  Google Scholar 

  84. Pepa GD, Brandi ML (2016) Microelements for bone boost: the last but not the least. Clin Cases Miner Bone Metab 13:181–185

    PubMed  Google Scholar 

  85. Laskus A, Zgadzaj A, Kolmas J (2018) Selenium-enriched brushite: a novel biomaterial for potential use in bone tissue engineering. Int J Mol Sci 19:4042

    PubMed Central  Google Scholar 

  86. Guan B, Yan R, Li R et al (2018) Selenium as a pleiotropic agent for medical discovery and drug delivery. Int J Nanomedicine 13:7473–7490

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Zeng H, Cao JJ, Combs GF Jr (2013) Selenium in bone health: roles in antioxidant protection and cell proliferation. Nutrients 5:97–110

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang H, Li Z, Dai C et al (2021) Antibacterial properties and mechanism of selenium nanoparticles synthesized by Providencia sp. DCX. Environ Res 194:110630

    Google Scholar 

  89. Kalishwaralal K, Jeyabharathi S, Sundar K et al (2018) A novel biocompatible chitosan-selenium nanoparticles (SeNPs) film with electrical conductivity for cardiac tissue engineering application. Mater Sci Eng C Mater Biol Appl 92:151–160

    CAS  PubMed  Google Scholar 

  90. Dorazilová J, Muchová J, Šmerková K et al (2020) Synergistic effect of chitosan and selenium nanoparticles on biodegradation and antibacterial properties of collagenous scaffolds designed for infected burn wounds. Nanomaterials 10:1971

    PubMed Central  Google Scholar 

  91. Jurkić LM, Cepanec I, Pavelić SK et al (2013) Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: new perspectives for therapy. Nutr Metab 10:2

    Google Scholar 

  92. Martin KR (2007) The chemistry of silica and its potential health benefits. J Nutr Health Aging 11:94–97

    CAS  PubMed  Google Scholar 

  93. Al-Harbi N, Mohammed H, Al-Hadeethi Y et al (2021) Silica-based bioactive glasses and their applications in hard tissue regeneration: a review. Pharmaceuticals 14:75

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Yang X, Li Y, Liu X et al (2016) The stimulatory effect of silica nanoparticles on osteogenic differentiation of human mesenchymal stem cells. Biomed Mater 12:015001

    Google Scholar 

  95. Uribe P, Johansson A, Jugdaohsingh R et al (2020) Soluble silica stimulates osteogenic differentiation and gap junction communication in human dental follicle cells. Sci Rep 10:9923

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Sim W, Barnard RT, Blaskovich MAT et al (2018) Antimicrobial silver in medicinal and consumer applications: a patent review of the past decade (2007–2017). Antibiotics 7:93

    CAS  PubMed Central  Google Scholar 

  97. Le Ouay B, Stellacci F (2015) Antibacterial activity of silver nanoparticles: a surface science insight. Nano Today 10:339–354

    Google Scholar 

  98. Panáček A, Kvítek L, Smékalová M et al (2018) Bacterial resistance to silver nanoparticles and how to overcome it. Nat Nanotechnol 13:65–71

    PubMed  Google Scholar 

  99. Möhler JS, Sim W, Blaskovich MAT et al (2018) Silver bullets: a new lustre on an old antimicrobial agent. Biotechnol Adv 36:1391–1411

    PubMed  Google Scholar 

  100. Dakal TC, Kumar A, Majumdar RS et al (2016) Mechanistic basis of antimicrobial actions of silver nanoparticles. Front Microbiol 7:1831

    PubMed  PubMed Central  Google Scholar 

  101. Jiménez M, Abradelo C, San Román J et al (2019) Bibliographic review on the state of the art of strontium and zinc based regenerative therapies. Recent developments and clinical applications. J Mater Chem B 7:1974–1985

    PubMed  Google Scholar 

  102. Neves N, Linhares D, Costa G et al (2017) In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: a systematic review. Bone Joint Res 6:366–375

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Kuang GM, Yau WP, Wu J et al (2015) Strontium exerts dual effects on calcium phosphate cement: accelerating the degradation and enhancing the osteoconductivity both in vitro and in vivo. J Biomed Mater Res A 103:1613–1621

    PubMed  Google Scholar 

  104. Zarins J, Pilmane M, Sidhom E et al (2016) Does local application of strontium increase osteogenesis and biomaterial osteointegration in osteoporotic and other bone tissue conditions: review of literature. Acta Chir Latv 16:17–23

    Google Scholar 

  105. Dahl SG, Allain P, Marie PJ et al (2001) Incorporation and distribution of strontium in bone. Bone 28:446–453

    CAS  PubMed  Google Scholar 

  106. Fonseca JE, Brandi ML (2010) Mechanism of action of strontium ranelate: what are the facts? Clin Cases Miner Bone Metab 7:17–18

    PubMed  PubMed Central  Google Scholar 

  107. Thomsen AR, Worm J, Jacobsen SE et al (2012) Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6–23 cells. J Pharmacol Exp Ther 343:638–649

    CAS  PubMed  Google Scholar 

  108. Treviño S, Díaz A, Sánchez-Lara E et al (2019) Vanadium in biological action: chemical, pharmacological aspects, and metabolic implications in diabetes mellitus. Biol Trace Elem Res 188:68–98

    PubMed  Google Scholar 

  109. O’Connor JP, Kanjilal D, Teitelbaum M et al (2020) Zinc as a therapeutic agent in bone regeneration. Materials 13:2211

    PubMed Central  Google Scholar 

  110. Singh A, Singh NB, Afzal S et al (2018) Zinc oxide nanoparticles: a review of their biological synthesis, antimicrobial activity, uptake, translocation and biotransformation in plants. J Mater Sci 53:185–201

    CAS  Google Scholar 

  111. Ciancaglini P, Pizauro JM, Curti C et al (1990) Effect of membrane moiety and magnesium ions on the inhibition of matrix-induced alkaline phosphatase by zinc ions. Int J Biochem 22:747–751

    CAS  PubMed  Google Scholar 

  112. Cho YE, Kwun IS (2018) Zinc upregulates bone-specific transcription factor Runx2 expression via BMP-2 signaling and Smad-1 phosphorylation in osteoblasts. J Nutr Health 51:23–30

    CAS  Google Scholar 

  113. Rodríguez JP, Rosselot G (2001) Effects of zinc on cell proliferation and proteoglycan characteristics of epiphyseal chondrocytes. J Cell Biochem 82:501–511

    PubMed  Google Scholar 

  114. Burgess D, Iversen T, Cottrell J (2018) Zinc chloride treatment in ATDC5 cells induces chondrocyte maturation. Int J Regen Med. https://doi.org/10.31487/j.RGM.2018.02.008

    Article  Google Scholar 

  115. Hie M, Tsukamoto I (2011) Administration of zinc inhibits osteoclastogenesis through the suppression of RANK expression in bone. Eur J Pharmacol 668:140–146

    CAS  PubMed  Google Scholar 

  116. Xie Y, He Y, Irwin PL et al (2011) Antibacterial activity and mechanism of action of zinc oxide nanoparticles against Campylobacter jejuni. Appl Environ Microbiol 77:2325–2331

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Sirelkhatim A, Mahmud S, Seeni A et al (2015) Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nanomicro Lett 7:219–242

    CAS  PubMed  Google Scholar 

  118. Bakshi PS, Selvakumar D, Kadirvelu K et al (2020) Chitosan as an environment friendly biomaterial—a review on recent modifications and applications. Int J Biol Macromol 150:1072–1083

    CAS  PubMed  Google Scholar 

  119. No HK, Meyers SP (1995) Preparation and characterization of chitin and chitosan-a review. J Aquat Food Prod Technol 4:27–52

    CAS  Google Scholar 

  120. Ogawa K, Oka K, Yui T (1993) X-ray study of chitosan-transition metal complexes. Chem Mater 5:726–728

    CAS  Google Scholar 

  121. Schlick S (1986) Binding sites of copper2+ in chitin and chitosan. An electron spin resonance study. Macromolecules 19:192–195

    CAS  Google Scholar 

  122. Gritsch L, Lovell C, Goldmann WH et al (2018) Fabrication and characterization of copper(II)-chitosan complexes as antibiotic-free antibacterial biomaterial. Carbohydr Polym 179:370–378

    CAS  PubMed  Google Scholar 

  123. Nie J, Wang Z, Hu Q (2016) Chitosan hydrogel structure modulated by metal ions. Sci Rep 6:36005

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Gritsch L, Liverani L, Lovell C et al (2020) Polycaprolactone electrospun fiber mats prepared using benign solvents: blending with copper(II)-chitosan increases the secretion of vascular endothelial growth factor in a bone marrow stromal cell line. Macromol Biosci 20:e1900355

    Google Scholar 

  125. Lin S, Chen L, Huang L et al (2015) Novel antimicrobial chitosan-cellulose composite films bioconjugated with silver nanoparticles. Ind Crops Prod 70:395–403

    CAS  Google Scholar 

  126. Rogina A, Vidović D, Antunović M et al (2020) Metal ion-assisted formation of porous chitosan-based microspheres for biomedical applications. Int J Polym Mater Polym Biomater. https://doi.org/10.1080/00914037.2020.1776283

    Article  Google Scholar 

  127. Palmer LC, Newcomb CJ, Kaltz SR et al (2008) Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel. Chem Rev 108:4754–4783

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Sprio S, Tampieri A, Landi E et al (2008) Physico-chemical properties and solubility behaviour of multi-substituted hydroxyapatite powders containing silicon. Mater Sci Eng C 28:179–187

    CAS  Google Scholar 

  129. Tao ZS, Bai BL, He XW et al (2016) A comparative study of strontium-substituted hydroxyapatite coating on implant’s osseointegration for osteopenic rats. Med Biol Eng Comput 54:1959–1968

    PubMed  Google Scholar 

  130. Capuccini C, Torricelli P, Sima F et al (2008) Strontium-substituted hydroxyapatite coatings synthesized by pulsed-laser deposition: in vitro osteoblast and osteoclast response. Acta Biomater 4:1885–1893

    CAS  PubMed  Google Scholar 

  131. Elrayah A, Zhi W, Feng S et al (2018) Preparation of micro/nano-structure copper-substituted hydroxyapatite scaffolds with improved angiogenesis capacity for bone regeneration. Materials 11:1516

    PubMed Central  Google Scholar 

  132. Maqbool M, Nawaz Q, Atiq Ur Rehman M et al (2021) Synthesis, characterization, antibacterial properties, and in vitro studies of selenium and strontium co-substituted hydroxyapatite. Int J Mol Sci 22:4246

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Khurshid Z, Safar MS, Hussain S et al (2020) Silver-substituted hydroxyapatite. In: Khan AS, Chaudhry AA (eds) Handbook of ionic substituted hydroxyapatite. Woodhead Publishing, England, pp 237–257

    Google Scholar 

  134. Thian ES, Konishi T, Kawanobe Y et al (2013) Zinc-substituted hydroxyapatite: a biomaterial with enhanced bioactivity and antibacterial properties. J Mater Sci Mater Med 24:437–445

    CAS  PubMed  Google Scholar 

  135. Dudareva M, Hotchen AJ, Ferguson J et al (2019) The microbiology of chronic osteomyelitis: changes over ten years. J Infect 79:189–198

    PubMed  Google Scholar 

  136. Li X, Nan K, Shi S et al (2012) Preparation and characterization of nano-hydroxyapatite/chitosan cross-linking composite membrane intended for tissue engineering. Int J Biol Macromol 50:43–49

    CAS  PubMed  Google Scholar 

  137. Frohbergh ME, Katsman A, Botta GP et al (2012) Electrospun hydroxyapatite-containing chitosan nanofibers crosslinked with genipin for bone tissue engineering. Biomaterials 33:9167–9178

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Chavanne P, Stevanovic S, Wüthrich A et al (2013) 3D printed chitosan/hydroxyapatite scaffolds for potential use in regenerative medicine. Biomed Tech. https://doi.org/10.1515/bmt-2013-4069

    Article  Google Scholar 

  139. Nezafati N, Faridi-Majidi R, Pazouki M et al (2019) Synthesis and characterization of a novel freeze-dried silanated chitosan bone tissue engineering scaffold reinforced with electrospun hydroxyapatite nanofiber. Polym Int 68:1420–1429

    CAS  Google Scholar 

  140. Gritsch L, Maqbool M, Mouriño V et al (2019) Chitosan/hydroxyapatite composite bone tissue engineering scaffolds with dual and decoupled therapeutic ion delivery: copper and strontium. J Mater Chem B 7:6109–6124

    CAS  PubMed  Google Scholar 

  141. Lei Y, Xu Z, Ke Q et al (2017) Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering. Mater Sci Eng C Mater Biol Appl 72:134–142

    CAS  PubMed  Google Scholar 

  142. Mansour SF, El-dek SI, Dorozhkin SV et al (2017) Physico-mechanical properties of Mg and Ag doped hydroxyapatite/chitosan biocomposites. New J Chem 41:13773–13783

    CAS  Google Scholar 

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Acknowledgements

The author would like to thank Dr. Cédric Bossard, Prof. Jonathan Lao and Dr. Isabel Orlando for their scientific support in shaping this chapter. Many thanks also to Mr. Ludovico Angelini for proof reading.

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Gritsch, L. (2022). Chitosan-Hydroxyapatite Composite Scaffolds for the Controlled Release of Therapeutic Metals Ions. In: Choi, A.H., Ben-Nissan, B. (eds) Innovative Bioceramics in Translational Medicine I. Springer Series in Biomaterials Science and Engineering, vol 17. Springer, Singapore. https://doi.org/10.1007/978-981-16-7435-8_9

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