Mosher Christopher Z, Spalazzi Jeffrey P, Lu Helen H
Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States.
Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States.
Methods. 2015 Aug;84:99-102. doi: 10.1016/j.ymeth.2015.03.029. Epub 2015 Apr 3.
A significant challenge to orthopaedic soft tissue repair is the biological fixation of autologous or allogeneic grafts with bone, whereby the lack of functional integration between such grafts and host bone has limited the clinical success of anterior cruciate ligament (ACL) and other common soft tissue-based reconstructive grafts. The inability of current surgical reconstruction to restore the native fibrocartilaginous insertion between the ACL and the femur or tibia, which minimizes stress concentration and facilitates load transfer between the soft and hard tissues, compromises the long-term clinical functionality of these grafts. To enable integration, a stratified scaffold design that mimics the multiple tissue regions of the ACL interface (ligament-fibrocartilage-bone) represents a promising strategy for composite tissue formation. Moreover, distinct cellular organization and phase-specific matrix heterogeneity achieved through co- or tri-culture within the scaffold system can promote biomimetic multi-tissue regeneration. Here, we describe the methods for fabricating a tri-phasic scaffold intended for ligament-bone integration, as well as the tri-culture of fibroblasts, chondrocytes, and osteoblasts on the stratified scaffold for the formation of structurally contiguous and compositionally distinct regions of ligament, fibrocartilage and bone. The primary advantage of the tri-phasic scaffold is the recapitulation of the multi-tissue organization across the native interface through the layered design. Moreover, in addition to ease of fabrication, each scaffold phase is similar in polymer composition and therefore can be joined together by sintering, enabling the seamless integration of each region and avoiding delamination between scaffold layers.
骨科软组织修复面临的一个重大挑战是自体或异体移植物与骨的生物固定，而这种移植物与宿主骨之间缺乏功能整合限制了前交叉韧带（ACL）和其他常见软组织重建移植物的临床成功率。当前的手术重建无法恢复ACL与股骨或胫骨之间天然的纤维软骨附着，而这种附着可使应力集中最小化并促进软硬组织之间的负荷传递，这损害了这些移植物的长期临床功能。为实现整合，模仿ACL界面（韧带-纤维软骨-骨）多个组织区域的分层支架设计是复合组织形成的一种有前景的策略。此外，通过在支架系统内进行共培养或三培养实现的独特细胞组织和阶段特异性基质异质性可促进仿生多组织再生。在此，我们描述了用于韧带-骨整合的三相支架的制造方法，以及在分层支架上对成纤维细胞、软骨细胞和成骨细胞进行三培养以形成韧带、纤维软骨和骨结构上连续且成分上不同区域的方法。三相支架的主要优点是通过分层设计重现了天然界面上的多组织结构。此外，除了易于制造外，每个支架阶段的聚合物组成相似，因此可以通过烧结连接在一起，实现每个区域的无缝整合并避免支架层之间的分层。
