PLGA Cage‐Like Structures Loaded with Sr/Mg‐Doped Hydroxyapatite for Repairing Osteoporotic Bone Defects

Abstract

Poly(lactic-co-glycolic acid) (PLGA)-based porous structures have a widespread application in bone defects. To solve its flaws in the bone application, hydroxyapatite (HA) is often introduced into PLGA-based systems, and ion doping endows HA with more biological activity. In osteoporotic bone defects, the decreased activity of osteoblasts and the hyperactive osteoclasts results in slow bone repair. Strontium (Sr) can promote bone regeneration and inhibit bone resorption and has been used in the treatment of osteoporosis. Magnesium (Mg) cannot only enhance the regeneration of bone tissue but also vessels. In this study,the aim is to fabricate a multifunctional porous structure that can promote osteogenesis, and angiogenesis and inhibit osteoclasts for repairing osteoporotic bone defects. PLGA cage-like structures loaded with Sr-and Mg-doped HA (Sr/Mg@HA/PLGA-CAS) are prepared; they have large pores, suitable hydrophilicity, and can continuously release Mg 2+ and Sr 2+ , which facilitate cell adhesion and growth. The results show that Sr/Mg@HA/PLGA-CAS can motivate the osteogenic activity of osteoblast precursor cells and angiogenic ability of endothelial cells, and suppress osteoclast differentiation in vitro. This study indicates that Sr/Mg@HA/PLGA-CAS can assist osteogenesis, and angiogenesis while restraining osteoclast differentiation, which may have a potential application value in osteoporotic bone defects.

Efforts to promote osteogenesis–angiogenesis coupling for bone tissue engineering

“…Micro-CT angio-graphy analysis revealed that at 4 weeks post-operation, the defects implanted with the PTM scaffold exhibited a greater formation of new blood vessels compared with scaffolds without Mg 2+ . In another case, Yu et al 40 prepared a PLGA cage structure loaded with Sr 2+ -and Mg 2+ -doped HA (Sr/ Mg@HA/PLGA-CAS). Results from in vitro cell experiments showed that the expression levels of ALP, BMP2, CoL-I, and OCN in the Sr/Mg@HA/PLGA-CAS group were 1.96-fold, 2.33fold, 15.32-fold, and 1.99-fold higher, respectively, compared with the PLGA-CAS group, indicating that the Sr/Mg@HA/ PLGA-CAS exhibited a strong osteogenic differentiation capability.…”

Biofunctionalisation strategies of material surface and the inspired biological effects for bone repair

“…Pham et al [84], Cao et al [85] and Zheng et al [86] prepared a hydroxyapatite coating with good osteogenic activity on the surface of the substrate material by plasma spraying. In our previous study Yu et al [87] prepared a porous PLGA cage microsphere loaded with strontium and magnesium-doped hydroxyapatite. This porous system improves cell adhesion, angiogenesis and osteogenic differentiation.…”

“…Anti-tumour and osteogenesis [78] Gel (Fe3O4/GOx/MgCO3 @PLGA) [79] Chemical composition Calcium phosphate PLGA cage-like structures loaded with Sr/Mg-Doped hydroxyapatite Promote osteogenic differentiation, induce angiogenesis, inhibit osteoclast differentiation [87] HA was coated with aluminium/bioplastic scaffolds by hydrothermal method…”

Enhancing the biological functionality of poly (lactic‐co‐glycolic acid) cage‐like structures through surface modification with micro‐ and nano‐sized hydroxyapatite particles

“…Previous studies have demonstrated that PLGA treated with HA can enhance hydrophilicity, neutralise the acidic microenvironment arising from PLGA degradation, and increase surface roughness, potentially enhancing cell adhesion [26,27]. Yu et al [28] incorporated strontium-doped HA (Sr@HA) and magnesium-doped HA (Mg@HA) onto alkali-treated PLGA cage-like structures (PLGA-CAS) to form multifunctional Sr/Mg@HA/PLGA-CAS microspheres. These microspheres demonstrated the ability to stimulate osteogenesis and angiogenesis while inhibiting osteoclastic differentiation.…”