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

Abstract

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 (Sr 2+ ) 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.

Injectable gelatin microspheres for osteomyelitis treatment: osteogenic and anti-inflammatory effect

“…4D) showed a close interaction of n-HA released from M with cells, followed by an internalization process via endocytosis pathways. n-HA can promote osteogenesis via the WNT/β-catenin pathway, favoring the induction of osteogenic transcription factor expression 75 (Fig. 13).…”

Ion incorporation into bone grafting materials

“…While excessive strontium can induce apoptosis, 121,122 it is typically incorporated in low concentrations as an osteoinductive element, often synergistically with other ions like zinc, silver, and magnesium, to bolster angiogenesis and osteogenesis. [123][124][125] F I G U R E 5 (A) Representative H&E images of the bone defect 7, 14, and 28 days after applying GBR membranes (Col, Col-MgO200, and Col-MgO500). The asterisks represent membranes, WB stands for Woven Bone.…”

“… 120 As such, Sr 2+ has emerged as a pivotal inorganic ion under investigation for the creation of innovative bone‐centric biomaterials. While excessive strontium can induce apoptosis, 121,122 it is typically incorporated in low concentrations as an osteoinductive element, often synergistically with other ions like zinc, silver, and magnesium, to bolster angiogenesis and osteogenesis 123–125 …”

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

“…Strontium is an essential trace element in the body, usually in the form of an ion. It is also an osteophilic element, and 99% of strontium is found in bone tissue and teeth. − Strontium ions, as bioactive ions possessing osteoinductive properties, have been applied to bone tissue engineering by numerous researchers in recent years. − An increase in strontium ions can activate the classical Wnt/β-catenin pathway by binding to calcium ion receptors on the cell membrane of osteoblasts. This enhances the expression of related osteogenic genes, such as RUNX2, ALP, and OPN, which promote the proliferation and differentiation of osteoblasts and increase bone formation .…”