Noory Parastoo, Farmani Ahmad Reza, Ai Jafar, Bahrami Naghmeh, Bayat Mohammad, Ebrahimi-Barough Somayeh, Farzin Ali, Shojaie Shima, Hajmoradi Hamed, Mohamadnia Abdolreza, Goodarzi Arash
Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.
J Biol Eng. 2025 May 20;19(1):48. doi: 10.1186/s13036-025-00514-y.
Despite the natural ability of bone repair, its limitations have led to advanced organic-inorganic-based biomimetic scaffolds and sustained drug release approaches. Particularly, dexamethasone (DEX), a widely used synthetic glucocorticoid, has been shown to increase the expression of bone-related genes during the osteogenesis process. This study aims to develop a hybrid 3D-printed scaffold for controlled delivery of dexamethasone. Hence, hybrid scaffolds were fabricated using a layer-by-layer 3D-printing of combined materials comprising polycaprolactone (PCL)-nanohydroxyapatite (nHA) composite, and DEX-loaded PCL microparticles embedded in the alginate-gelatin hydrogel. Encapsulation efficiency, loading capacity, and in vitro kinetics of DEX release were evaluated. Osteogenic differentiation of human endometrial mesenchymal stem cells (hEnMSCs) on DEX-loaded hybrid scaffolds was assessed by evaluating osteogenic gene expression levels (collagen I, osteonectin, RUNX2), alkaline phosphatase (ALP) activity, and scaffold mineralization. The hybrid scaffolds exhibited favorable morphology, mechanical-properties, biocompatibility, and biodegradability, enhancing osteogenesis of hEnMSCs. DEX-loaded PCL microparticles within hybrid scaffolds exhibited a controlled release pattern and promoted osteogenic differentiation during the sustained release period through a significant increase in osteonectin and COL1A1 expression. Also, increased mineralization was demonstrated by SEM and alizarin red staining. This study proposes that drug-loaded 3D-printed hybrid organic-inorganic nanocomposite scaffolds are promising for advanced bone tissue engineering applications.
尽管骨修复具有天然能力，但其局限性促使了先进的有机-无机基仿生支架和持续药物释放方法的发展。特别是，地塞米松（DEX）作为一种广泛使用的合成糖皮质激素，已被证明在成骨过程中可增加骨相关基因的表达。本研究旨在开发一种用于地塞米松控释的混合3D打印支架。因此，采用逐层3D打印的方法制备了混合支架，该支架由聚己内酯（PCL）-纳米羟基磷灰石（nHA）复合材料以及嵌入藻酸盐-明胶水凝胶中的载DEX的PCL微粒组成。评估了DEX的包封效率、载药量和体外释放动力学。通过评估成骨基因表达水平（I型胶原蛋白、骨连接蛋白、RUNX2）、碱性磷酸酶（ALP）活性和支架矿化情况，评估了载DEX混合支架上的人子宫内膜间充质干细胞（hEnMSCs）的成骨分化。混合支架表现出良好的形态、力学性能、生物相容性和生物降解性，增强了hEnMSCs的成骨作用。混合支架内载DEX的PCL微粒呈现出控释模式，并在持续释放期间通过显著增加骨连接蛋白和COL1A1的表达促进了成骨分化。此外，扫描电子显微镜和茜素红染色显示矿化增加。本研究表明，载药3D打印混合有机-无机纳米复合支架在先进的骨组织工程应用中具有广阔前景。
