Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland.
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
Biomaterials. 2019 Jan;188:63-73. doi: 10.1016/j.biomaterials.2018.09.044. Epub 2018 Oct 4.
Biological scaffolds generated from tissue-derived extracellular matrix (ECM) are commonly used clinically for soft tissue regeneration. Such biomaterials can enhance tissue-specific differentiation of adult stem cells, suggesting that structuring different ECMs into multi-layered scaffolds can form the basis of new strategies for regenerating damaged interfacial tissues such as the osteochondral unit. In this study, mass spectrometry is used to demonstrate that growth plate (GP) and articular cartilage (AC) ECMs contain a unique array of regulatory proteins that may be particularly suited to bone and cartilage repair respectively. Applying a novel iterative freeze-drying method, porous bi-phasic scaffolds composed of GP ECM overlaid by AC ECM are fabricated, which are capable of spatially directing stem cell differentiation in vitro, promoting the development of graded tissues transitioning from calcified cartilage to hyaline-like cartilage. Evaluating repair 12-months post-implantation into critically-sized caprine osteochondral defects reveals that these scaffolds promote regeneration in a manner distinct to commercial control-scaffolds. The GP layer supports endochondral bone formation, while the AC layer stimulates the formation of an overlying layer of hyaline cartilage with a collagen fiber architecture better recapitulating the native tissue. These findings support the use of a bi-layered, tissue-specific ECM derived scaffolds for regenerating spatially complex musculoskeletal tissues.
组织衍生细胞外基质（ECM）生成的生物支架常用于软组织再生的临床治疗。这些生物材料可以增强成体干细胞的组织特异性分化，这表明将不同的 ECM 结构化为多层支架可以为再生受损界面组织（如骨软骨单位）提供新策略的基础。在这项研究中，质谱法被用于证明生长板（GP）和关节软骨（AC）的 ECM 含有独特的调节蛋白阵列，这些蛋白可能分别特别适合于骨和软骨修复。应用一种新颖的迭代冷冻干燥方法，制备了由 GP ECM 覆盖的 AC ECM 组成的多孔双相支架，这些支架能够在体外空间引导干细胞分化，促进从钙化软骨到透明软骨样软骨的分级组织的发育。在植入山羊临界大小的骨软骨缺损 12 个月后进行评估，发现这些支架以不同于商业对照支架的方式促进再生。GP 层支持软骨内骨形成，而 AC 层刺激透明软骨的上层形成，其胶原纤维结构更好地再现了天然组织。这些发现支持使用双层组织特异性 ECM 衍生支架来再生空间复杂的肌肉骨骼组织。
