Calcium Phosphate-Based Nanomaterials: Preparation, Multifunction, and Application for Bone Tissue Engineering

Abstract

Calcium phosphate is the main inorganic component of bone. Calcium phosphate-based biomaterials have demonstrated great potential in bone tissue engineering due to their superior biocompatibility, pH-responsive degradability, excellent osteoinductivity, and similar components to bone. Calcium phosphate nanomaterials have gained more and more attention for their enhanced bioactivity and better integration with host tissues. Additionally, they can also be easily functionalized with metal ions, bioactive molecules/proteins, as well as therapeutic drugs; thus, calcium phosphate-based biomaterials have been widely used in many other fields, such as drug delivery, cancer therapy, and as nanoprobes in bioimaging. Thus, the preparation methods of calcium phosphate nanomaterials were systematically reviewed, and the multifunction strategies of calcium phosphate-based biomaterials have also been comprehensively summarized. Finally, the applications and perspectives of functionalized calcium phosphate biomaterials in bone tissue engineering, including bone defect repair, bone regeneration, and drug delivery, were illustrated and discussed by presenting typical examples.

Keywords: bioimaging; bone tissue engineering; calcium phosphate; drug delivery; multifunction; nanomaterials.

Figure 1

Schematic representation of wet chemical precipitation for the preparation of calcium phosphate-based biomaterial. Reprinted with permission from Ref. [24], Copyright 2019, American Chemical Society (Washington, DC, USA).

Figure 2

Schematic representation of solvothermal synthesis for the preparation of calcium phosphate-based biomaterial. Reprinted with permission from Ref. [31], Copyright 2016, Royal Society of Chemistry (London, UK).

Figure 3

Schematic representation of the classical sol-gel procedure for the preparation of calcium phosphate-based bio-material. Reprinted with permission from Ref. [35], Copyright 2020, Elsevier (Amsterdam, The Netherlands).

Figure 4

Schematic representation of the microwave-assisted procedure for the preparation of calcium phosphate-based biomaterials. Reprinted with permission from Ref. [45], Copyright 2020, Elsevier.

Figure 5

Schematic representation of the sonochemical synthesis for the preparation of calcium phosphate-based biomaterials. Reprinted with permission from Ref. [52], Copyright 2018, Nature Publishing Group (Berlin, Germany).

Figure 6

Schematic representation of the enzyme-assisted method for the preparation of organic-inorganic nanocomposites. Reprinted with permission from Ref. [58], Copyright 2018, Wiley (Hoboken, NJ, USA).

Figure 7

Strategies for the component engineering of nano-calcium phosphate-based biomaterials. (a) Calcium phosphate-based biomaterial coated with heparin to crosslink with ferulic acid; reprinted with permission from Ref. [97], Copyright 2021, MDPI (Basel, Switzerland). (b) The crosslinked porous biphasic calcium phosphate loading more BMP-2; reprinted with permission from Ref. [95]. (c) The structure of the calcium phosphate-based biomaterial influenced by the pH value, leading to the drug release; reprinted with permission from Ref. [98], Copyright 2019, Elsevier.

Figure 8

Strategies for calcium phosphate-based material loading genes. (a) Calcium phosphate-loading DNA fixed in a scaffold to promote BMP-2 protein; reprinted with permission from Ref. [96], Copyright 2018, Elsevier. (b) The nucleic acid-loaded nanoparticles, combining nucleic acid molecule-loaded CaP nanoparticles with a Gln-Ochi chitosan coating to avoid aggregating; reprinted with permission from Ref. [108], Copyright 2015, Royal Society of Chemistry.

Figure 9

Strategies for mixing metal ions with calcium phosphate. Calcium phosphate cement mixed with Ba/Sr ions to achieve bone regeneration. Reprinted with permission from Ref. [114], Copyright 2021, Royal Society of Chemistry.

Figure 10

Calcium phosphate composite materials with different properties for bone repair. (a) Calcium phosphate scaffolds loaded with ginger and garlic extracts can improve bone regeneration and osteogenic differentiation (* p < 0.05; ** 0.05 < p < 0.01; and *** p < 0.01); reprinted with permission from Ref. [116], Copyright 2022, American Chemical Society. (b) Calcium phosphate materials were combined with Zn/Fe ions to turn micropores into a dispersed solid; reprinted with permission from Ref. [117], Copyright 2019, Royal Society of Chemistry.

Figure 11

Multi-application in the imaging area. (a) Calcium phosphate-based materials used in bioimaging; reprinted with permission from Ref. [124], Copyright 2012, Elsevier. (b) Simple flow chart of calcium phosphate composite gadolinium and for CT and MRI bone defect repair evaluation. Green arrows indicate the bright area which appears in the middle of the implant on the MRI acquisitions after 4 weeks from the surgery. Red arrow displays the calcium phosphate cements that become indistinguishable from the surrounding bone after 8 weeks from implantation in vivo; reprinted with permission from Ref. [126], Copyright 2018, Wiley.

Figure 12

Strategies for calcium phosphate-based materials to kill cancer cells. (a) Reversal of the multidrug resistance of tumors by combining calcium phosphate with Se element; reprinted with permission from Ref. [130], Copyright 2020, Elsevier. (b) Construction of calcium phosphate and TiO₂ to promote cancer therapy; reprinted with permission from Ref. [142], Copyright 2021, Wiley.