Ahmed Tamer A E, Hincke Maxwell T
Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technology Applications (SRTA City), Universities and Research Centers District, Alexandria, Egypt.
Division of Clinical and Functional Anatomy, Department of Cellular and Molecular Medicine, University of Ottawa, ttawa, ON, Canada.
Histol Histopathol. 2014 Jun;29(6):669-89. doi: 10.14670/HH-29.669. Epub 2014 Jan 23.
Restoration of articular cartilage function and structure following pathological or traumatic damage is still considered a challenging problem in the orthopaedic field. Currently, tissue engineering-based reconstruction of articular cartilage is a feasible and continuously developing strategy to restore structure and function. Successful articular cartilage tissue engineering strategy relies largely on several essential components including cellular component, supporting 3D carrier scaffolding matrix, bioactive agents, proper physical stimulants, and safe gene delivery. Designing the right formulations from these components remain the main concern of the orthopaedic community. Utilization of mesenchymal stem cells (MSCs) for articular cartilage tissue engineering is continuously increasing compared to use of chondrocytes. Various sources of MSCs have been investigated including adipose tissue, amniotic fluid, blood, bone marrow, dermis, embryonic stem cells, infrapatellar fat pad, muscle, periosteum, placenta, synovium, trabecular bone, and umbilical cord. MSCs derived from bone marrow and umbilical cord are currently in different phases of clinical trials. A wide range of matrices have been investigated to develop tissue engineering-based strategies including carbohydrate-based scaffolds (agarose, alginate, chitosan/chitin, and hyaluronate), protein-based scaffolds (collagen, fibrin, and gelatin), and artificial polymers (polyglycolic acid, polylactic acid, poly(lactic-co-glycolic acid), polyethylene glycol, and polycaprolactone). Collagen-based scaffolds and photopolymerizable PEG-based scaffolds are currently in different phases of clinical trials. TGF-β1, TGF-β3, BMP-2, and hypoxic environment are the recommended bioactive agents to induce optimum chondrogenesis of MSCs, while TGF-β1, TGF-β3, SOX-9, BMP-2, and BMP-7 genes are the best candidate for gene delivery to MSCs. Electromagnetic field and the combination of shear forces/dynamic compression are the best maturation-promoting physical stimulants.
在骨科领域，病理性或创伤性损伤后关节软骨功能和结构的恢复仍然是一个具有挑战性的问题。目前，基于组织工程的关节软骨重建是恢复结构和功能的一种可行且不断发展的策略。成功的关节软骨组织工程策略在很大程度上依赖于几个关键要素，包括细胞成分、支持性三维载体支架基质、生物活性剂、适当的物理刺激物和安全的基因传递。从这些成分中设计出合适的配方仍然是骨科界主要关注的问题。与使用软骨细胞相比，间充质干细胞（MSCs）在关节软骨组织工程中的应用正在不断增加。人们已经研究了多种MSCs来源，包括脂肪组织、羊水、血液、骨髓、真皮、胚胎干细胞、髌下脂肪垫、肌肉、骨膜、胎盘、滑膜、松质骨和脐带。源自骨髓和脐带的MSCs目前正处于不同阶段的临床试验中。为了开发基于组织工程的策略，人们已经研究了多种基质，包括碳水化合物基支架（琼脂糖、藻酸盐、壳聚糖/几丁质和透明质酸盐）、蛋白质基支架（胶原蛋白、纤维蛋白和明胶）以及人工聚合物（聚乙醇酸、聚乳酸、聚（乳酸-共-乙醇酸）、聚乙二醇和聚己内酯）。基于胶原蛋白的支架和可光聚合的聚乙二醇基支架目前正处于不同阶段的临床试验中。转化生长因子-β1（TGF-β1）、转化生长因子-β3（TGF-β3）、骨形态发生蛋白-2（BMP-2）和低氧环境是诱导MSCs最佳软骨生成的推荐生物活性剂，而TGF-β1、TGF-β3、SRY-box转录因子9（SOX-9）、BMP-2和骨形态发生蛋白-7（BMP-7）基因是向MSCs进行基因传递的最佳候选基因。电磁场以及剪切力/动态压缩的组合是最佳的促进成熟的物理刺激物。
