Yang Jin, Fatima Kanwal, Zhou Xiaojun, He Chuanglong
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine; College of Biological Science and Medical Engineering, Donghua University, Shanghai, China.
Biomater Transl. 2024 Mar 28;5(1):69-83. doi: 10.12336/biomatertransl.2024.01.007. eCollection 2024.
The repair of large load-bearing bone defects requires superior mechanical strength, a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly integrate optimal microarchitecture, mechanical robustness, vascularisation, and osteoinductive biological responses to effectively address these critical load-bearing bone defects. To confront this challenge, three-dimensional (3D) printing technology was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded, evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold. The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation. Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium, revealing the superior cell migration and tube network formation. The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold. Furthermore, the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination, demonstrating enhanced osteogenic and angiogenic performance. This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering, providing a potential solution for effective bone defect repair.
大承重骨缺损的修复需要卓越的机械强度，而单一的水凝胶支架无法实现这一目标。其目的是无缝整合最佳的微观结构、机械强度、血管化以及骨诱导生物反应，以有效解决这些关键的承重骨缺损问题。为应对这一挑战，采用三维（3D）打印技术制备了一种基于聚己内酯（PCL）的一体化支架。在3D打印的PCL支架孔隙内，嵌入了一种与负载甲状旁腺激素（PTH）肽的介孔二氧化硅纳米颗粒（PTH@MSNs）复合的甲基丙烯酸明胶（GelMA）/甲基丙烯酸丝素蛋白（SFMA）水凝胶，演变成一种多孔的PTH@MSNs/GelMA/SFMA/PCL（PM@GS/PCL）支架。通过细致的化学和物理表征，证实了制造这种具有定制分层结构的功能性支架的可行性。压缩测试表明，复合支架的强度令人印象深刻，达到17.81±0.83MPa。此外，通过使用人脐静脉内皮细胞的Transwell和管形成试验评估了PM@GS/PCL支架的体外血管生成潜力，结果显示其具有优异的细胞迁移和管网形成能力。使用骨髓间充质干细胞进行的茜素红和碱性磷酸酶染色试验清楚地表明，该支架具有强大的成骨分化特性。此外，利用微型计算机断层扫描和组织学检查在大鼠股骨缺损模型上研究了该支架的骨修复潜力，结果表明其具有增强的成骨和血管生成性能。本研究提出了一种有前景的策略，用于制造与微环境匹配的骨组织工程复合支架，为有效修复骨缺损提供了一种潜在的解决方案。
