Advances in synthesis of calcium phosphate crystals with controlled size and shape

Acta Biomater. 2014 Oct;10(10):4071-102. doi: 10.1016/j.actbio.2014.06.017. Epub 2014 Jun 20.


Calcium phosphate (CaP) materials have a wide range of applications, including biomaterials, adsorbents, chemical engineering materials, catalysts and catalyst supports and mechanical reinforcements. The size and shape of CaP crystals and aggregates play critical roles in their applications. The main inorganic building blocks of human bones and teeth are nanocrystalline CaPs; recently, much progress has been made in the application of CaP nanocrystals and their composites for clinical repair of damaged bone and tooth. For example, CaPs with special micro- and nanostructures can better imitate the biomimetic features of human bone and tooth, and this offers significantly enhanced biological performances. Therefore, the design of CaP nano-/microcrystals, and the shape and hierarchical structures of CaPs, have great potential to revolutionize the field of hard tissue engineering, starting from bone/tooth repair and augmentation to controlled drug delivery devices. Previously, a number of reviews have reported the synthesis and properties of CaP materials, especially for hydroxyapatite (HAp). However, most of them mainly focused on the characterizations and physicochemical and biological properties of HAp particles. There are few reviews about the control of particle size and size distribution of CaPs, and in particular the control of nano-/microstructures on bulk CaP ceramic surfaces, which is a big challenge technically and may have great potential in tissue engineering applications. This review summarizes the current state of the art for the synthesis of CaP crystals with controlled sizes from the nano- to the macroscale, and the diverse shapes including the zero-dimensional shapes of particles and spheres, the one-dimensional shapes of rods, fibers, wires and whiskers, the two-dimensional shapes of sheets, disks, plates, belts, ribbons and flakes and the three-dimensional (3-D) shapes of porous, hollow, and biomimetic structures similar to biological bone and tooth. In addition, this review will also summarize studies on the controlled formation of nano-/microstructures on the surface of bulk ceramics, and the preparation of macroscopical bone grafts with 3-D architecture nano-/microstructured surfaces. Moreover, the possible directions of future research and development in this field, such as the detailed mechanisms behind the size and shape control in various strategies, the importance of theoretical simulation, self-assembly, biomineralization and sacrificial precursor strategies in the fabrication of biomimetic bone-like and enamel-like CaP materials are proposed.

Keywords: Calcium phosphates; Crystals; Shape; Size; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry*
  • Bone Substitutes / chemical synthesis
  • Bone Substitutes / chemistry*
  • Calcium Phosphates / chemistry*
  • Composite Resins / chemical synthesis
  • Composite Resins / chemistry*
  • Crystallization
  • Humans
  • Nanoparticles / chemistry*


  • Bone Substitutes
  • Calcium Phosphates
  • Composite Resins
  • calcium phosphate