Compartmental control of mineral formation: adaptation of a biomineralization strategy for biomedical use

Abstract

A common biomineralization strategy is the use of lipid vesicle compartments to sequester ions, control ion transport, and to control the shape and size of inorganic mineral particles deposited within developing tissues. In this paper, we describe an adaptation of this bioinspired strategy for inducing rapid formation of calcium phosphates for potential medical and dental use. Calcium and inorganic phosphate salts were separately loaded into temperature-sensitive liposomes composed of 90% 1,2-bis(palmitoyl)- sn-glycero-3-phosphocholine and 10% 1,2-bis(myristoyl)- sn-glycero-3-phosphocholine. Leakage of calcium and inorganic phosphate from liposomes stored at room temperature was negligible over a period of several weeks. Calcium-loaded liposomes released entrapped calcium when heated to 36–37°C, while phosphate-loaded liposomes released entrapped inorganic phosphate (P i) at slightly lower temperatures (33–34°C). Release of entrapped ions at this temperature was due to increased permeability of phospholipid bilayers at the lipid chain melting temperature. Aqueous suspensions containing mixtures of calcium and P i-loaded liposomes formed calcium phosphate mineral when heated to 37°C, as indicated by a rapid drop in suspension pH from 7 to approximately 5. This result was consistent with diffusion of both calcium and phosphate ions out of the liposomes and their reaction to form calcium phosphate mineral. Such a strategy could be used in medical and dental procedures to induce rapid inorganic mineral formation from an injectable liposome-containing fluid. This was illustrated by applying a liposome suspension to warm human dentin and enamel surfaces, which resulted in deposition of calcium phosphate minerals onto the tissue substrates.