In vivo evaluation of a multiphased scaffold designed for orthopaedic interface tissue engineering and soft tissue-to-bone integration
In vivo evaluation of a multiphased scaffold designed for orthopaedic interface tissue engineering and soft tissue-to-bone integration
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DOI：
10.1002/jbm.a.32073
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发表时间：
2008-07-01
影响因子：
4.9
通讯作者：
Lu, Helen H.
中科院分区：
文献类型：
--
作者：
Spalazzi, Jeffrey P.;Dagher, Elias;Lu, Helen H.
实现功能性移植物与软骨下骨的整合对骨科软组织修复和重建提出了重大挑战。前交叉韧带（ACL）等软组织通过纤维软骨界面与骨结合，从而最大限度地减少应力集中并介导软硬组织之间的负荷转移。我们建议，生物固定可以通过再生生物或合成ACL移植物上的纤维软骨界面来实现。本研究的重点是在体内评价的分层支架预先设计，以模拟在ACL-骨界面发现的多组织过渡。具体而言，支架由三个不同但连续的相组成：A相用于韧带形成，B相用于界面，C相用于骨区域。界面相关细胞类型，特别是成纤维细胞、软骨细胞和成骨细胞，将在该支架上进行三重培养，并在皮下无胸腺大鼠模型中评价8周内细胞类型和相特异性基质异质性的形成以及纤维软骨形成。脱细胞支架以及与成纤维细胞和成骨细胞共培养的支架将用作对照。发现三相支架支持多谱系细胞相互作用以及组织浸润和体内丰富的基质产生。此外，在支架上诱导了受控的阶段特异性基质异质性，在三培养组中形成了不同的矿物和纤维软骨样组织区域。细胞接种对宿主浸润和基质加工都有积极影响，与无细胞对照相比，这也转化为接种组的机械性能增加。总之，结合细胞分布的空间控制的仿生和多相设计使得能够在分层支架上进行多组织再生，并且证明了再生软组织移植物和骨之间的界面的潜力。(C)2008 Wiley Periodicals，Inc.
Achieving functional graft integration with subchondral bone poses a significant challenge for orthopaedic soft tissue repair and reconstruction. Soft tissues such as the anterior cruciate ligament (ACL) integrate with bone through a fibrocartilage interface, which minimizes stress concentrations and mediates load transfer between soft and hard tissues. We propose that biological fixation can be achieved by regenerating this fibrocartilage interface on biological or synthetic ACL grafts. This study focuses on the in vivo evaluation of a stratified scaffold predesigned to mimic the multitissue transition found at the ACL-to-bone interface. Specifically, the scaffold consists of three distinct yet continuous phases: Phase A for ligament formation, Phase B for the interface, and Phase C for the bone region. Interface-relevant cell types, specifically fibroblasts, chondrocytes, and osteoblasts, will be tri-cultured on this scaffold, and the formation of cell type- and phase-specific matrix heterogeneity as well as fibrocartilage formation will be evaluated over 8 weeks in a subcutaneous athymic rat model. Acellular scaffolds as well as scaffolds co-cultured with fibroblasts and osteoblasts will serve as controls. It was found that the triphasic scaffold supported multilineage cellular interactions as well as tissue infiltration and abundant matrix production in vivo. In addition, controlled phase-specific matrix heterogeneity was induced on the scaffold, with distinct mineral and fibrocartilage-like tissue regions formed in the tri-cultured group. Cell seeding had a positive effect on both host infiltration and matrix elaboration, which also translated into increased mechanical properties in the seeded groups compared to the acellular controls. In summary, the biomimetic and multiphasic design coupled with spatial control of cell distribution enables multitissue regeneration on the stratified scaffold, and demonstrates the potential for regenerating the interface between soft tissue grafts and bone. (C) 2008 Wiley Periodicals, Inc.