Strontium Ion-Functionalized Nano-Hydroxyapatite/Chitosan Composite Microspheres Promote Osteogenesis and Angiogenesis for Bone Regeneration

Critical-size bone defects are an important problem in clinical practice, which usually occurs in severe trauma, or tumor resection, and cannot heal completely and autonomously. Implantation of grafts is often required to promote the regeneration of critical-size bone defects. Metal ions play an important role in human health, as they affect the body’s metabolism and the tissue function. Strontium ions (Sr2+) can promote osteogenesis and angiogenesis. Herein, we prepared nano-hydroxyapatite (nHA)/chitosan (CS) composite microspheres with a uniform particle size distribution and an extracellular matrix-like nanofiber structure using microfluidic technology and direct alkali-induced gelation. Strontium ions were stably added into the microspheres by using polydopamine (PDA) to chelate metal ions forming a bone repair material (nHA/CS@PDA-Sr) with good bioactivity. The coordination reaction of PDA can effectively control the release of strontium ions and avoid the negative effects caused by the high strontium concentration. Our in vitro experiments showed that the composite microspheres had good biocompatibility and that the PDA coating promotes cell adhesion. The slow release of strontium ions can effectively promote mesenchymal stem cells osteogenic differentiation and the vascularization of endothelial cells. In addition, we injected composite microspheres into cranial defects of rats to evaluate osseointegration in vivo. The results showed that nHA/CS@PDA-Sr could effectively promote bone regeneration in the defect area. This study demonstrates that composite microspheres stimulate bone repair providing a promising way for bone-defect regeneration

Polydopamine-Functionalized Strontium Alginate/Hydroxyapatite Composite Microhydrogel Loaded with Vascular Endothelial Growth Factor Promotes Bone Formation and Angiogenesis

Critical-size bone defects are a common and intractable clinical problem that typically requires filling in with surgical implants to facilitate bone regeneration. Considering the limitations of autologous bone and allogeneic bone in clinical applications, such as secondary damage or immunogenicity, injectable microhydrogels with osteogenic and angiogenic effects have received considerable attention. Herein, polydopamine (PDA)-functionalized strontium alginate/nanohydroxyapatite (Sr-Alg/nHA) composite microhydrogels loaded with vascular endothelial growth factor (VEGF) were prepared using microfluidic technology. This composite microhydrogel released strontium ions stably for at least 42 days to promote bone formation. The PDA coating can release VEGF in a controlled manner, effectively promote angiogenesis around bone defects, and provide nutritional support for new bone formation. In in vitro experiments, the composite microhydrogels had good biocompatibility. The PDA coating greatly improves cell adhesion on the composite microhydrogel and provides good controlled release of VEGF. Therefore, this composite microhydrogel effectively promotes osteogenic differentiation and vascularization. In in vivo experiments, composite microhydrogels were injected into critical-size bone defects in the skull of rats, and they were shown by microcomputed tomography and tissue sections to be effective in promoting bone regeneration. These findings demonstrated that this novel microhydrogel effectively promotes bone formation and angiogenesis at the site of bone defects

A pH-Responsive Yolk-Like Nanoplatform for Tumor Targeted Dual-Mode Magnetic Resonance Imaging and Chemotherapy

Incorporation of T₁ and T₂ contrast material in one nanosystem performing their respective MR contrast role and simultaneously serving as an efficient drug delivery system (DDS) has a significant potential application for clinical diagnosis and chemotherapy of cancer. However, inappropriate incorporation always encountered many issues, such as low contact area of T₁ contrast material with water-proton, inappropriate distance between T₂ contrast material and water molecule, and undesirable disturbance of T₂ contrast material for T₁ imaging. Those issues seriously limited the T₁ or T₂ contrast effect. In this work, we developed a yolk-like Fe₃O₄@Gd₂O₃ nanoplatform functionalized by polyethylene glycol and folic acid (FA), which could efficiently exert their tumor targeted T₁–T₂ dual-mode MR imaging and drug delivery role. First, this nanoplatform possessed a high longitudinal relaxation rate (<i>r</i>₁) (7.91 mM^–1 s^–1) and a stronger transverse relaxation rate (<i>r</i>₂) (386.5 mM^–1 s^–1) than that of original Fe₃O₄ (268.1 mM^–1 s^–1). Second, cisplatin could be efficiently loaded into this nanoplatform (112 mg/g) and showed pH-responsive release behavior. Third, this nanoplatform could be effectively internalized by HeLa cells with time and dosage dependence. Fourth, the FA receptor-mediated nanoplatform displayed excellent T₁–T₂ dual mode MR contrast enhancement and anticancer activity both <i>in vitro</i> and <i>in vivo</i>. Fifth, no apparent toxicity for vital organs was observed with systemic delivery of the nanoplatform <i>in vivo</i>. Thus, this nanoplatform could be a potential nanotheranostic for tumor targeted T₁–T₂ dual-mode MR imaging and chemotherapy