Bas Onur, De-Juan-Pardo Elena M, Meinert Christoph, D'Angella Davide, Baldwin Jeremy G, Bray Laura J, Wellard R Mark, Kollmannsberger Stefan, Rank Ernst, Werner Carsten, Klein Travis J, Catelas Isabelle, Hutmacher Dietmar W
Institute of Health and Biomedical Innovation, Centre for Regenerative Medicine, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia.
Biofabrication. 2017 May 12;9(2):025014. doi: 10.1088/1758-5090/aa6b15.
Articular cartilage from a material science point of view is a soft network composite that plays a critical role in load-bearing joints during dynamic loading. Its composite structure, consisting of a collagen fiber network and a hydrated proteoglycan matrix, gives rise to the complex mechanical properties of the tissue including viscoelasticity and stress relaxation. Melt electrospinning writing allows the design and fabrication of medical grade polycaprolactone (mPCL) fibrous networks for the reinforcement of soft hydrogel matrices for cartilage tissue engineering. However, these fiber-reinforced constructs underperformed under dynamic and prolonged loading conditions, suggesting that more targeted design approaches and material selection are required to fully exploit the potential of fibers as reinforcing agents for cartilage tissue engineering. In the present study, we emulated the proteoglycan matrix of articular cartilage by using highly negatively charged star-shaped poly(ethylene glycol)/heparin hydrogel (sPEG/Hep) as the soft matrix. These soft hydrogels combined with mPCL melt electrospun fibrous networks exhibited mechanical anisotropy, nonlinearity, viscoelasticity and morphology analogous to those of their native counterpart, and provided a suitable microenvironment for in vitro human chondrocyte culture and neocartilage formation. In addition, a numerical model using the p-version of the finite element method (p-FEM) was developed in order to gain further insights into the deformation mechanisms of the constructs in silico, as well as to predict compressive moduli. To our knowledge, this is the first study presenting cartilage tissue-engineered constructs that capture the overall transient, equilibrium and dynamic biomechanical properties of human articular cartilage.
从材料科学的角度来看，关节软骨是一种软网络复合材料，在动态加载过程中对承重关节起着关键作用。其复合结构由胶原纤维网络和水合蛋白聚糖基质组成，赋予了该组织复杂的力学性能，包括粘弹性和应力松弛。熔体静电纺丝书写技术可用于设计和制造医用级聚己内酯（mPCL）纤维网络，以增强用于软骨组织工程的软水凝胶基质。然而，这些纤维增强构建体在动态和长时间加载条件下表现不佳，这表明需要更具针对性的设计方法和材料选择，以充分发挥纤维作为软骨组织工程增强剂的潜力。在本研究中，我们通过使用高负电荷的星形聚乙二醇/肝素水凝胶（sPEG/Hep）作为软基质来模拟关节软骨的蛋白聚糖基质。这些软水凝胶与mPCL熔体静电纺丝纤维网络相结合，表现出与天然软骨类似的力学各向异性、非线性、粘弹性和形态，并为体外人软骨细胞培养和新软骨形成提供了合适的微环境。此外，还开发了一个使用有限元法p版本（p-FEM）的数值模型，以便进一步深入了解构建体在计算机模拟中的变形机制，并预测压缩模量。据我们所知，这是第一项展示软骨组织工程构建体的研究，该构建体能够捕捉人关节软骨的整体瞬态、平衡和动态生物力学特性。
