Repair of osteochondral defects with rehydrated freeze-dried oligo[poly(ethylene glycol) fumarate] hydrogels seeded with bone marrow mesenchymal stem cells in a porcine model
Lim, Chin Tat
Afizah, Mohd Hassan
Chian, Kerm Sin
Mikos, Antonios G.
Hui, James Hoi Po
Date of Issue2013
School of Mechanical and Aerospace Engineering
Current surgical techniques for osteochondral injuries in young active patients are inadequate clinically. Novel strategies in tissue engineering are continuously explored in this area. Despite numerous animal studies that have shown encouraging results, very few large-scale clinical trials have been done to address this area of interest. To facilitate the eventual translation from rabbit to human subjects, we have performed a study using bone marrow-derived mesenchymal stem cell (BMSC)–oligo[poly(ethylene glycol) fumarate] (OPF) hydrogel scaffold in a porcine model. Our objective was to analyze the morphology of BMSCs seeded into rehydrated freeze-dried OPF hydrogel and in vivo gross morphological and histological outcome of defects implanted with the BMSCs-OPF scaffold in a porcine model. The analyses were based on magnified histologic sections for different types of cartilage repair tissues, the outcome of the subchondral bone, scaffold, and statistical assessment of neotissue-filling percentage, cartilage phenotype, and Wakitani scores. The morphology of the BMSCs seeded into the rehydrated freeze-dried OPF scaffold was observed 24 h after cell seeding, through the phase-contrast microscope. The three-dimensional and cross-sectional structure of the fabrication was analyzed through confocal microscopy and histological methods, respectively. The BMSCs remained viable and were condensed into many pellet-like cell masses with a diameter ranging from 28.5 to 298.4 (113.5±47.9) μm in the OPF scaffold. In vivo osteochondral defect repair was tested in 12 defects created in six 8-month-old Prestige World Genetics micropigs. The implantation of scaffold alone was used for control. Gross morphological, histological, and statistical analyses were performed at 4 months postoperatively. The scaffold–MSC treatment led to 99% defect filling, with 84% hyaline-like cartilage at 4 months, which was significantly (p<0.0001) more than the 54% neotissue filling and 39% hyaline-like cartilage obtained in the scaffold-only group. The implantation of BMSCs in freeze-dried OPF hydrogel scaffold, which created a conducive environment for cell infiltration and clustering, could fully repair chondral defects with hyaline-like cartilage. This protocol provides a clinically feasible procedure for osteochondral defect treatment.
Tissue engineering - Part A
© 2013 Mary Ann Liebert. This paper was published in Tissue Engineering Part A and is made available as an electronic reprint (preprint) with permission of Mary Ann Liebert. The paper can be found at the following official DOI: [http://dx.doi.org/10.1089/ten.tea.2012.0621]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.