Chondrocyte morphology as an indicator of collagen network integrity

ABSTRACT

Osteochondral allograft (OCA) transplantation offers an attractive treatment option as it can be used to repair large cartilage defects that otherwise would not heal. The currently accepted criterion for OCA selection for joint reconstruction is the percentage of viable chondrocytes, but this criterion alone may not be sufficient to ensure structural integrity and functional performance of allografts following transplantation. We sought to determine an additional parameter that indicates matrix integrity. We used multi-photon microscopy to quantitatively assess chondrocyte viability, chondrocyte shape, and collagen structure of articular cartilage of OCAs. Chondrocyte shape varied considerably in otherwise macroscopically healthy-looking OCAs with good (>90%) cell viability. Shape varied from the expected ellipsoidal form found in healthy cartilage, to excessively elongated and flattened cells that often contained multiple cytoplasmic processes reminiscent of those observed in fibroblasts. Chondrocytes with abnormal morphology were associated with degradation of their pericellular matrix and disruption of the collagen fiber orientation, reflected by an increase in heterogeneity of second harmonic signal intensity. Cell shape may be an important marker for collagen network integrity in articular cartilage in general and OCAs specifically. We propose that, aside from cell viability, cell shape may be used as an additional criterion measure for the selection of OCAs. OCAs selected for transplantation based on these criteria showed good graft-host integration post-operation. In view of the rapid and nondestructive nature of the current approach, it may be suitable for clinical application in the future.

KEYWORDS:

• Second harmonic generation imaging
• two-photon excitation imaging
• chondrocytes
• collagen fiber network
• osteochondral allograft
• osteoarthritis

Acknowledgments

Open Access funding provided by the Qatar National Library.

We would like to express our gratitude to Dr Mark Heard and Dr Ian Lo for providing patient follow-up data and acknowledge our collaboration with the Southern Alberta Organ and Tissue Donation Program, Alberta Health Services.

Data availability

All data used in this study are available from the corresponding author upon request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the Joint Transplantation Program at the McCaig Institute for Bone and Joint Health, University of Calgary, as well as the Calgary Health Trust.