Development of Sponge-Like Monodisperse PLGA/Alginate Core-Shell Microsphere Delivery Device to Enable Precisely Controlled Release of Magnesium Ions for In-Situ Bone Regeneration

Professor Yeung, Kelvin Wai Kwok   (Project Coordinator (PC))

Professor Cheung Kenneth Man Chee   (Co-Investigator)

Mr Lin Zhengjie   (Co-Investigator)

Dr Wu Jun   (Co-Investigator)

17

2020-01-09

2021-06-30

391209

Development of Sponge-Like Monodisperse PLGA/Alginate Core-Shell Microsphere Delivery Device to Enable Precisely Controlled Release of Magnesium Ions for In-Situ Bone Regeneration

Alginate Core-Shell, Development, In-Situ Bone Regeneration, Magnesium Ions, Precisely Controlled Release, Sponge-Like Monodisperse PLGA

Others - Medicine, Dentistry and Health

InP/001/20

Innovation and Technology Fund Internship Programme

2020

Completed

In some orthopaedic conditions, such as large segmental bone defects and osteoporotic bone fractures, bone regeneration or repair is challenging. Therefore, orthopaedic surgeons have considered applying biological agents, e.g., recombinant human bone morphogenetic protein 2 (rh-BMP2) and parathyroid hormone (PTH), as off-label drugs to stimulate bone repair. Despite reports of successful cases using rh-BMP2, cost and safety remain major concerns. Anti-catabolic drugs, e.g., bisphosphonates (BPs), are commonly used to prevent bone loss in osteoporosis, but they are suspected of leading to low-energy or stress bone fracture, gastrointestinal problems, esophagus inflammation and jawbone osteonecrosis after long-term administration. Thus, there is a crucial need to develop another safe, economical and efficient method of stimulating bone regeneration. Our team has demonstrated that a low concentration of magnesium ions (i.e., 50～200 ppm) can effectively promote the proliferation and differentiation of pre-osteoblasts and the up-regulation of osteogenic genes in vitro and during new bone formation under in vivo conditions. Therefore, we propose a novel method of stimulating local bone regeneration via the constant and controlled delivery of Mg2+ in an in vivo microenvironment. To facilitate in situ bone regeneration, an injectable magnesium-based microspheres comprised of an FDA-approved biopolymer, namely poly (lactic-co-glycolic acid) (PLGA); alginate and magnesium oxide nano-particles is designed using microfluidic techniques. In the pilot study, we have successfully fabricated two types of magnesium-based microspheres (e.g. PLGA/MgO microspheres and PLGA/MgO-alginate core-shell microspheres). The results suggest that the constant and controlled release of Mg2+ from PLGA/MgO-alginate core-shell microspheres demonstrates not only enhanced cell attachment and spreading, higher cell viability and proliferation and the increased differentiation of osteoblasts but also the up-regulation of osteogenic gene expression. In addition, the magnesium core-shell microsphere can stimulate in-situ bone regeneration in vivo in terms of the growth of total bone volume, bone mineral density (BMD), and trabecular thickness in rat models after 8 weeks of operation. The results have already been published in Biomaterials journal. Hence, the current proposal aims at translating the research outcomes to treat a commonly seen orthopaedic problem: osteoporotic large segmental bone defect. If successful, these magnesium-based core-shell microspheres could effectively stimulate new bone formation locally, thereby greatly reducing the burden on patients and the related socioeconomic costs due to prolonged hospitalization.