Abstract

In the 1970s, morphological evidence collected by electron microscopy linked mineral deposition (“calcification” or “mineralization”) in newly-forming bone to membrane-encapsulated particles of a diameter of approximately 100 nm (50–200 nm) that were called “matrix vesiscles”. As the characterisation of these vesicles progressed towards their biochemical composition, the role of lipids in the biomineralization process appeared to be crucial. In particular, a group of cell-membrane phospholipids were identified as major players in the crystal formation process. Indeed, in the 1980s it became clear that phosphatidylserine, together with proteins of the annexin family, was among the most important molecules in binding calcium ions and that this phospholipid was involved in the regulation of the early stages of mineralization in vivo. During the same period of time, the number of surgical implantations of orthopaedic, dental and maxilo-facial devices requiring full integration with the treated bone prompted the study of new functionalisation molecules able to establish a stable bonding with the mineral phase of the host tissue. In the late 1990s studies started that aimed at exploiting the potential of calcium-binding phospholipids and, in particular, of the phosphatidylserine as functionalisation molecules to improve the osteointegration of artificial implants. Later, papers have been published that show the potential of the phophatidylserine and phosphatidylserine-mimicking coating technology to promote calcification both in vitro and in vivo. The promising results support the future clinical application of these novel osteointegrative biomaterials.

Highlights

  • In the 1970s, morphological evidence collected by electron microscopy linked mineral deposition (“calcification” or “mineralization”) in newly-forming bone to membrane-encapsulated particles of a diameter of approximately 100 nm (50–200 nm) that were called “matrix vesiscles”

  • These authors have summarised the biomineralization potential of these structures in the composition of their nucleation core that they reported to be composed of three principal interacting constituents: (i) the amorphous calcium phosphate (ACP), (ii) calcium-phosphate-lipid complexes (CPLX) formed by ACP partially combined with PS and (iii) annexin A5 (AnxA5)

  • During a period of about thirty years PS has been recognized as one important molecule involved in the mineralization process in bone formation

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Summary

Bone structure and function

Bone plays fundamental mechanical and protective functions in vertebrates. These functions are successfully exerted by the unique combination of a mineral phase deposited on a proteic template. Ossification is the formation of bone by the activity of cells termed “osteoblasts” which deposit the proteinaceous matrix (the osteoid tissue) and later promote the deposition of minerals which they take from the blood. This process of mineral deposition is called “mineralization”. Bone turn-over is finely tuned by biochemical signaling (hormonal, autocrine and paracrine) and is the result of a complex series of biochemical and cellular interactions These events contradict the apparently inert nature of the bony tissue. These properties are enhanced by the intimate bonding of the organic and mineral phase to provide the unique tensile and compressive properties of the bony tissues [1,12]

Matrix Vesicles
Phospholipids and Calcification
A Role for Phosphatidyl-Serine
Technological Application of Artificial MVs
Calcium-binding phospholipids as coating molecules of medical implants
In vivo response to phosphatidyl-serine coating
Findings
Conclusions

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