Effect of Bone Marrow Mesenchymal Stem Cells derived Exosomes loaded in Collagen Hydrogel on Bone Regeneration in male Rat Calvarial Critical-Size Bone Defect

Sara Hamza, Marwa Noureldin, Lamia Heikal, Enas Omar, Hagar Abdel Fattah
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Abstract

INTRODUCTION: Expanded bone damage in defects of critical size demands interventions for the complete regeneration. However, limitations of the previous strategies include reduced availability of autograft donors. The therapeutic efficacy of exosomes has been extensively studied in numerous circumstances such as wound healing, bone and periodontal regeneration. AIM: This research work aimed to test the efficacy of collagen thermoresponsive hydrogel loaded by BMMSC-derived exosomes on bone regeneration in rats’ calvarial critical-size bone defects. MATERIALS AND METHODS: Twenty albino rats were allocated into 2 groups, 10 rats each. Group I-collagen hydrogel (COLL), Group II-(COLL+ exosomes). Calvarial critical-size bone defects were surgically created in all groups. The defects in Group I were filled with collagen hydrogel, and in Group II were filled with exosomes-loaded collagen hydrogel. Rats were euthanized after 4 and 8 weeks, and the calvariae were collected and processed. The regenerated bone was evaluated by histology, histomorphometry, and immunohistochemical expression of the bone formation marker osteocalcin. RESULTS: Analyzing the new bone using histology and histomorphometry revealed an enhanced quantity and pattern of bone formation in defects augmented with collagen hydrogel loaded by exosomes compared to the bare collagen hydrogel group after 4 weeks. However, after 8 weeks no significant difference was detected between groups. Immunohistochemical expression of osteocalcin showed higher values in group II (Coll + exosomes) in comparison to group I collagen hydrogel (COLL). CONCLUSION: Bone marrow mesenchymal stem cells derived exosomes loaded collagen thermoresponsive hydrogel provides a precious substitution to cell-based therapy in bone regenerative procedures.
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胶原水凝胶中负载的骨髓间充质干细胞衍生外泌体对雄性大鼠髑髅临界大小骨缺损骨再生的影响
引言:在严重缺损的情况下,需要对扩大的骨损伤进行干预,以实现完全再生。然而,以往策略的局限性包括自体移植供体的可用性降低。外泌体的治疗功效已在伤口愈合、骨和牙周再生等多种情况下得到广泛研究。目的:本研究旨在测试由 BMMSC 衍生的外泌体负载的胶原热致伸缩性水凝胶对大鼠腓骨临界大小骨缺损的骨再生效果。材料与方法:将 20 只白化大鼠分为 2 组,每组 10 只。I 组--胶原水凝胶(COLL),II 组--(COLL+ 外泌体)。所有组均通过手术创建犊骨临界大小骨缺损。第一组用胶原水凝胶填充缺损,第二组用外泌体填充胶原水凝胶。大鼠分别在 4 周和 8 周后安乐死,收集并处理小腿骨。通过组织学、组织形态学和骨形成标志物骨钙素的免疫组化表达对再生骨进行评估。结果:使用组织学和组织形态计量学分析新骨发现,与裸胶原水凝胶组相比,4周后使用外泌体填充胶原水凝胶的缺损处骨形成的数量和模式都有所增加。然而,8 周后,各组之间未发现明显差异。与第一组胶原水凝胶(COLL)相比,第二组(胶原+外泌体)的骨钙素免疫组化表达值更高。结论:骨髓间充质干细胞衍生的外泌体负载胶原热致伸缩水凝胶为骨再生手术中的细胞疗法提供了宝贵的替代品。
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