Strontium ranelate-loaded sodium alginate/collagen hydrogel promotes bone defect repair in osteoarthritis

doi:10.12307/2024.363

Abstract

Abstract: BACKGROUND: Cartilage degeneration and subchondral bone damage are the main pathological features of osteoarthritis, and treatment based on this pathological feature will be a promising improvement for osteoarthritis.
OBJECTIVE: To design and study an annotated strontium ranelate-loaded drug delivery system and to observe its therapeutic effect on promoting cartilage repair and improving subchondral bone structure in osteoarthritis.
METHODS: (1) In vitro experiment: Strontium ranelate was loaded into sodium alginate/collagen hydrogel matrix to construct in situ drug delivery system, and the in vitro slow release performance of the system was characterized. Strontium ranelate-loaded sodium alginate/collagen hydrogel (experimental group) and alginate sodium/collagen hydrogel (control group) were co-cultured with bone marrow mesenchymal stem cells, respectively, and cultured cells were used as a blank control group to detect cell proliferative activity. After chondroblast-induced differentiation, saffron O staining, Alcian blue staining and RT-qPCR were performed respectively. The two hydrogels were co-cultured with osteoblasts, and the cultured cells were used as a blank control group for immunofluorescence staining and RT-qPCR. (2) In vivo experiment: A total of 18 adult SD rats were selected and the model of right posterior knee osteoarthritis was established by the method of medial meniscectomy. After 1 week, the rats were divided into three groups by the random number table method: The blank group did not receive any treatment. The control group was injected with sodium alginate/collagen hydrogel in the knee, and the experimental group was injected with strontium ranelate-loaded sodium alginate/collagen hydrogel, with 6 rats in each group. After 6 weeks, the samples were subjected to Micro-CT scanning, hematoxylin-eosin staining, saffron O-solid green staining and immunofluorescence staining.
RESULTS AND CONCLUSION: (1) In vitro experiment: Strontium ranelate-loaded sodium alginate/collagen hydrogel had porous microstructure and sustainable release of strontium ranelate. At 21 days, the cumulative release reached (60.89±0.58)%. Bone marrow mesenchymal stem cell staining showed that both hydrogels had good cytocompatibility. The results of the CCK-8 assay demonstrated that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote the proliferation of bone marrow mesenchymal stem cells. The results of Safranin O staining, Alcian blue staining, immunofluorescence staining and RT-qPCR exhibited that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote chondrogenic differentiation of bone marrow mesenchymal stem cells. Immunofluorescence staining and RT-qPCR revealed that strontium ranelate-loaded sodium alginate/collagen hydrogel could decrease bone resorptivity by increasing the ratio of osteophosphorin/nuclear factor κB receptor activator ligand. (2) In vivo experiment: Micro-CT scan verified that compared with the blank group and control group, the subchondral bone volume fraction and bone mineral density of the knee of rats were increased in the experimental group (P < 0.05, P < 0.01). Histological staining displayed that compared with the blank group and control group, the knee cartilage injury was significantly reduced; the expression of type II collagen was promoted, and the expression of matrix metalloproteinase 2 protein was inhibited in the experimental group (P < 0.05, P < 0.01). (3) These results confirm that the strontium ranelate-loaded sodium alginate/collagen hydrogel can promote the repair of cartilage defects in osteoarthritis and reconstruct the complex interface between cartilage and subchondral bone.

Key words: osteoarthritis, drug delivery system, sodium alginate/collagen hydrogel, strontium ranelate, subchondral bone, cartilage repair

CLC Number:

Su Kunyang, Chen Bineng, Chen Yiliang, Jin Shaofeng. Strontium ranelate-loaded sodium alginate/collagen hydrogel promotes bone defect repair in osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(10): 1568-1574.

Figures/Tables 9

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