Translation of a solution-based biomineralization concept into a carrier-based delivery system via the use of expanded-pore mesoporous silica

Abstract

Mineralization of collagen fibrils using solution-based systems containing biomimetic analogs of matrix proteins to stabilize supersaturated calcium phosphate solutions have been predictably achieved in-vitro. Solution-based systems have limitations when used for in-situ remineralization of human hypomineralized tissues because periodic replenishment of the mineralizing solution is infeasible. A carrier-based platform designed for delivering mineral precursors would be highly desirable. In the present work, mesoporous silica nanoparticles with expanded pores (eMSN; 14.8 nm) were synthesized. Polyacrylic acid-stabilized amorphous calcium phosphate (PA-ACP) was generated from a supersaturated calcium and phosphate ion-containing solution, and chosen as the model mineralizing phase. After amine functionalization (AF) of the eMSN through a post-grafting method, the positively-charged AF-eMSN enabled loading of PA-ACP by electrostatic interaction. In-vitro cytotoxicity testing indicated that PA-ACP@AF-eMSN was highly biocompatible. The release kinetics of mineralization precursors from PA-ACP@AF-eMSN was characterized by an initial period of rapid calcium and phosphate release that reached a plateau after 120 hr. Intrafibrillar mineralization was examined using a 2-D fibrillar collagen model; successful mineralization was confirmed using transmission electron microscopy. To date, this is the first endeavor that employs expanded-pore mesoporous silica to deliver polymer-stabilized intermediate precursors of calcium phosphate for intrafibrillar mineralization of collagen. The carrier-based delivery system bridges the gap between contemporary solution-based biomineralization concepts and clinical practice, and is useful for in-situ remineralization of bone and teeth.

Titania coating of mesoporous silica nanoparticles for improved biocompatibility and drug release within blood vessels

“…We have previously demonstrated the uptake of nanomaterials by ECs [5,6], including mesoporous silica nanoparticles (MSNs), and their highlighted potential use as drug delivery platforms for vasodilator drugs [7]. In particular, MSNs hold great promise as drug delivery vehicles [8,9]. They can be synthesised with a narrow particle size distribution and a regular pore structure that can accommodate guest molecules, while the exterior surface can be functionalised to allow targeted drug delivery [10,11].…”

Angiogenic Effects of Collagen/Mesoporous Nanoparticle Composite Scaffold Delivering VEGF165

“…Collagen type I has been widely studied as tissue engineering scaffolds [ 8 ]. Mainly the fibrillar form of collagen with sufficient self-assembly process could improve the physical and biochemical stability [ 9 – 11 ]. As the signaling molecule, we focused on angiogenic factors.…”

In vitro remineralization of hybrid layers using biomimetic analogs

“…However, no solution-based systems can yet be used clinically and basic science may here only pave the way for the development of future usable techniques (Zhong et al, 2015;Luo et al, 2016).…”