Prolonged in vitro precultivation alleviates post-implantation inflammation and promotes stable subcutaneous cartilage formation in a goat model
- 2 December 2016
- journal article
- research article
- Published by IOP Publishing in Biomedical Materials
- Vol. 12 (1), 015006
- https://doi.org/10.1088/1748-605x/12/1/015006
Abstract
Synthetic biodegradable scaffolds such as polylactic acid coated polyglycolic acid (PLA-PGA) are especially suitable for engineering shaped cartilage such as auricle, but they induce a serious inflammatory reaction particularly in the immunologically aggressive subcutaneous site, leading to resorption of the engineered autologous cartilage. Our previous study in a rabbit model has demonstrated 2 weeks of in vitro precultivation could significantly alleviate the post-implantation inflammation induced by PLA-PGA engineered cartilaginous grafts, but reproduction of this result failed in a preclinical goat model. The aims of the current study were to investigate whether prolonged in vitro precultivation could form a mature cartilaginous graft to resist the acute host response and promote stable subcutaneous cartilage formation in a preclinical goat model. Goat chondrocytes were seeded onto PLA-PGA scaffolds, in vitro precultivated for 2, 4, 8, and 12 weeks, and then implanted subcutaneously in autologous goats for 1 and 8 weeks. The in vitro engineered cartilage (vitro-EC) was examined histologically (hematoxylin and eosin, safranin-O, collagen II). The 1 week explants were examined histologically and stained for CD3, CD68, collagen I, and apoptosis. The 8 week explants were evaluated by histology, wet weight, volume, glycosaminoglycan (GAG) quantification and Young's modulus. With prolonged in vitro time, the quality of vitro-EC improved and the amount of scaffold residue decreased; more pronounced cartilage formation with fewer immune cells (CD3 and CD68 positive), apoptotic cells, and less collagen I expression were observed in explants that had been in vitro precultivated for a longer period. The subcutaneously regenerated neocartilage became more mature after prolonged implantation. These results suggested that prolonged in vitro precultivation allowed formation of a mature cartilaginous graft to resist the acute host response and promoted stable subcutaneous cartilage formation in autologous goats. These findings may provide useful reference for engineering auricle, trachea, nose, and eyelid shaped cartilage, for example.Keywords
Funding Information
- Shanghai Rising-Star Program (16QB1400600)
- National Natural Science Foundation of China (31271046, 81371703, 81371701, 31400830, 81571823)
This publication has 32 references indexed in Scilit:
- Cell-based tissue engineering strategies used in the clinical repair of articular cartilageBiomaterials, 2016
- Orthopedic tissue regeneration: cells, scaffolds, and small moleculesDrug Delivery and Translational Research, 2015
- Repair and tissue engineering techniques for articular cartilageNature Reviews Rheumatology, 2014
- Regeneration of human-ear-shaped cartilage by co-culturing human microtia chondrocytes with BMSCsBiomaterials, 2014
- Successful Creation of Tissue-Engineered Autologous Auricular Cartilage in an Immunocompetent Large Animal ModelTissue Engineering, Part A, 2014
- Tissue Engineering in the TracheaThe Anatomical Record, 2013
- Ear Reconstruction through Tissue EngineeringAdvances in oto-rhino-laryngology, 2010
- In vitro engineering of human ear-shaped cartilage assisted with CAD/CAM technologyBiomaterials, 2010
- Reconstruction of auricular cartilage using tissue-engineering techniquesOperative Techniques in Otolaryngology-Head and Neck Surgery, 2008
- Transplantation of Chondrocytes Utilizing a Polymer-Cell Construct to Produce Tissue-Engineered Cartilage in the Shape of a Human EarPlastic and Reconstructive Surgery, 1997