Journal
BIOMATERIALS
Volume 174, Issue -, Pages 1-16Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.05.011
Keywords
Core-shell microspheres; Microfluidic capillary device; Precisely controlled magnesium ion release; Biocompatibility; Bone regeneration
Funding
- General Research Fund of Hong Kong Research Grant Council [17214516, N_HKU725/16]
- Hong Kong Innovation Technology Fund [ITS/147/15]
- Hong Kong Health and Medical Research Fund [03142446]
- HKU Seed Fund for Translational and Applied Research [201611160006]
- Sanming Project of Medicine in Shenzhen Team of Excellence in Spinal Deformities and Spinal Degeneration Disease [SZSM201612055]
- National Natural Science Foundation of China [31370957]
- Shenzhen Science and Technology Funding [JCYJ20160429190821781, JCYJ20160429185449249]
- Guangdong Scientific Plan [2014A030313743]
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A range of magnesium ions (Mg2+) used has demonstrated osteogenic tendency in vitro. Hence, we propose to actualize this concept by designing a new system to precisely control the Mg2+ delivery at a particular concentration in vivo in order to effectively stimulate in-situ bone regeneration. To achieve this objective, a monodisperse core-shell microsphere delivery system comprising of poly (lactic-co-glycolic acid) (PLGA) biopolymer, alginate hydrogel, and magnesium oxide nano-particles has been designed by using customized microfluidic capillary device. The PLGA-MgO sponge-like spherical core works as a reservoir of Mg2+ while the alginate shell serves as physical barrier to control the outflow of Mg2+ at similar to 50 ppm accurately for 2 weeks via its adjustable surface micro-porous network. With the aid of controlled release of Mg2+, the new core-shell microsphere system can effectively enhance osteoblastic activity in vitro and stimulate in-situ bone regeneration in vivo in terms of total bone volume, bone mineral density (BMD), and trabecular thickness after operation. Interestingly, the Young's moduli of formed bone on the core-shell microsphere group have been restored to similar to 96% of that of the surrounding matured bone. These findings indicate that the concept of precisely controlled release of Mg2+ may potentially apply for in-situ bone regeneration clinically. (C) 2018 Elsevier Ltd. All rights reserved.
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