Elgamily Mahitabe, Denewar Mona, Emam Ahmed A, Othman Basma Hamed, Sultan Nessma
Faculty of Dentistry, Mansoura University, Mansoura, Egypt.
Faculty of Dentistry, Mansoura National University, Gamasa, Egypt.
Odontology. 2025 Sep 21. doi: 10.1007/s10266-025-01203-4.
This study was carried out to assess the potential effect of a glycogen synthase kinase-3 inhibitor tideglusib hydrogel formulation on bone regeneration and to compare it with Ethoss a beta tricalcium phosphate alloplastic bone substitute mixed with calcium sulphate in vitro and in vivo. Bone marrow mesenchymal stem cells (BMMSCs) were isolated from New Zealand white rabbit tibias and characterized by flowcytometric analysis. Sodium alginate hydrogel loaded with tideglusib was formulated and underwent characterization by scanning electron microscopy, the fourier transform infrared and zeta potential. Extraction media from both tideglusib hydrogel and Ethoss were prepared then MTT, alizarin red (ARS) and scratch wound assays were performed. Two bone defects were trephined in tibias of eighteen adult healthy rabbits, which were classified into three groups: group 1, bone defects were left untreated; group 2, each defect was filled with tideglusib hydrogel; group 3, each defect was filled with Ethoss. Animals were sacrificed after three and six weeks. Histological and immunohistochemical analyses using alkaline phosphatase (ALP) and osteopontin (OPN) were performed to assess bone regeneration. The tideglusib hydrogel group expressed higher mineral deposition than Ethoss group using ARS but without significant difference, stronger stimulatory effect on the migration of BMMSCs was also evident with significant narrowing of the wound area. New bone tissue was progressively seen bridging and filling the defects with significantly higher ALP and OPN expression in hydrogel group. Tideglusib hydrogel formulation exhibited superior bone regenerative potential in comparison to beta tricalcium phosphate alloplastic bone substitute.
本研究旨在评估糖原合酶激酶-3抑制剂替格列汀水凝胶制剂对骨再生的潜在作用，并在体外和体内将其与Ethoss（一种与硫酸钙混合的β-磷酸三钙异体骨替代物）进行比较。从新西兰白兔胫骨中分离出骨髓间充质干细胞（BMMSCs），并通过流式细胞术分析进行表征。制备了负载替格列汀的海藻酸钠水凝胶，并通过扫描电子显微镜、傅里叶变换红外光谱和zeta电位进行表征。制备了替格列汀水凝胶和Ethoss的提取培养基，然后进行MTT、茜素红（ARS）和划痕试验。在18只成年健康兔的胫骨上钻两个骨缺损，分为三组：第1组，骨缺损不治疗；第2组，每个缺损用替格列汀水凝胶填充；第3组，每个缺损用Ethoss填充。在3周和6周后处死动物。使用碱性磷酸酶（ALP）和骨桥蛋白（OPN）进行组织学和免疫组织化学分析以评估骨再生。使用ARS检测，替格列汀水凝胶组的矿物质沉积高于Ethoss组，但无显著差异，对BMMSCs迁移的刺激作用也更明显，伤口面积显著缩小。逐渐可见新骨组织桥接并填充缺损，水凝胶组中ALP和OPN表达显著更高。与β-磷酸三钙异体骨替代物相比，替格列汀水凝胶制剂具有更好的骨再生潜力。
