Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model

被引:46
作者
Lam, J. [1 ]
Lu, S. [1 ]
Lee, E. J. [1 ]
Trachtenberg, J. E. [1 ]
Meretoja, V. V. [1 ]
Dahlin, R. L. [1 ]
van den Beucken, J. J. J. P. [2 ]
Tabata, Y. [3 ]
Wong, M. E. [4 ]
Jansen, J. A. [2 ]
Mikos, A. G. [1 ]
Kasper, F. K. [1 ]
机构
[1] Rice Univ, Dept Bioengn, Houston, TX 77251 USA
[2] Radboud Umc, Dept Biomat, Nijmegen, Netherlands
[3] Kyoto Univ, Inst Frontier Med Sci, Dept Biomat, Kyoto, Japan
[4] Univ Texas Sch Dent, Div Oral & Maxillofacial Surg, Dept Surg, Houston, TX USA
基金
美国国家卫生研究院;
关键词
Chondrogenic; Osteogenic; Pre-differentiation; Osteochondral repair; Hydrogel; Mesenchymal stem cell; ARTICULAR-CARTILAGE DEFECTS; TRANSFORMING GROWTH-FACTOR-BETA-1; TISSUE; SCAFFOLDS; RELEASE; KNEE; REGENERATION; STIMULATION; CONSTRUCTS; GENERATION;
D O I
10.1016/j.joca.2014.06.035
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Objective: To investigate the ability of cell-laden bilayered hydrogels encapsulating chondrogenically and osteogenically (OS) pre-differentiated mesenchymal stem cells (MSCs) to effect osteochondral defect repair in a rabbit model. By varying the period of chondrogenic pre-differentiation from 7 (CG7) to 14 days (CG14), the effect of chondrogenic differentiation stage on osteochondral tissue repair was also investigated. Methods: Rabbit MSCs were subjected to either chondrogenic or osteogenic pre-differentiation, encapsulated within respective chondral/subchondral layers of a bilayered hydrogel construct, and then implanted into femoral condyle osteochondral defects. Rabbits were randomized into one of four groups (MSC/MSC, MSC/OS, CG7/OS, and CG14/OS; chondral/subchondral) and received two similar constructs bilaterally. Defects were evaluated after 12 weeks. Results: All groups exhibited similar overall neo-tissue filling. The delivery of OS cells when compared to undifferentiated MSCs in the subchondral construct layer resulted in improvements in neo-cartilage thickness and regularity. However, the addition of CG cells in the chondral layer, with OS cells in the subchondral layer, did not augment tissue repair as influenced by the latter when compared to the control. Instead, CG7/OS implants resulted in more irregular neo-tissue surfaces when compared to MSC/OS implants. Notably, the delivery of CG7 cells, when compared to CG14 cells, with OS cells stimulated morphologically superior cartilage repair. However, neither osteogenic nor chondrogenic pre-differentiation affected detectable changes in subchondral tissue repair. Conclusions: Cartilage regeneration in osteochondral defects can be enhanced by MSCs that are chondrogenically and osteogenically pre-differentiated prior to implantation. Longer chondrogenic pre-differentiation periods, however, lead to diminished cartilage repair. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1291 / 1300
页数:10
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