16.2.4 - Bilayered Extracellular Matrix Derived Scaffolds with Tailored Pore Architecture for Osteochondral Defect Repair
- D. Browe (Dublin 2, IE)
- D. Browe (Dublin 2, IE)
- P. Diaz Payno (Dublin, IE)
- F. Freeman (Dublin, IE)
- R. Schipani (Dublin, IE)
- R. Burdis (Dublin, IE)
- D. Ahern (Dublin, IE)
- J. Nulty (Dublin, IE)
- S. Guler (Dublin, IE)
- L. Randall (Dublin, IE)
- C. Buckley (Dublin, IE)
- P. Brama (Dublin, IE)
- D. Kelly (Dublin, IE)
Abstract
Purpose
The overall goal of this study was to develop an ‘off-the-shelf’, bilayered scaffold for osteochondral defect repair that combines tissue-specific extracellular matrix (ECM) derived biomaterials to drive zonal repair with a tailored pore architecture to recapitulate the hierarchical collagen structure of articular cartilage (AC).
Methods and Materials
Freeze-dried anisotropic scaffolds were produced from solubilized ECM using a novel methodology through (i) modifying freeze-drying kinetics and (ii) controlling direction of heat transfer. 6x6mm osteochondral defects were created in the trochlear ridge of goats. Joints were assigned to one of the two groups: Empty control or AC-Bone ECM-derived bilayered scaffold. Tissue repair was evaluated at 6 months.
Results
In this study we developed a novel freeze-drying method which concurrently increased the mean pore size and aligned the pore orientation within the scaffolds. This fabrication method resulted in significant increases in glycosaminoglycan deposition by MSCs and enhanced collagen fiber alignment in the scaffolds (Fig 1A). We established that ECM biomaterials derived from solubilized bone were optimal for bone repair applications when compared to scaffolds derived from other musculoskeletal tissues in a subcutaneous mouse model (Fig 1B). Finally, we observed that implantation of an “off-the-shelf” bilayered ECM scaffold improved tissue repair outcomes in a caprine model (Fig 1C). The scaffold supported the development of a cartilage repair tissue that possessed high levels of GAG and type II collagen. Furthermore, the scaffold was found to support the development of a native AC-like collagen alignment through the depth of the repair tissue and to significantly reduce the collagen fibre dispersion in the superficial layer of AC to levels comparable with native tissue controls.
Conclusion
This scaffold technology represents a promising clinical option for the repair of osteochondral defects which could be used as a standalone scaffold or could be used in combination with autologous cells or growth factors to enhance repair.