Chondrocyte repopulation of the zone of death induced by osteochondral harvest.
OBJECTIVE
Harvesting osteochondral grafts results in a zone of chondrocyte death (ZCD) in and around the periphery of the graft, creating a barrier for chondrocytes to migrate to the graft periphery, thus limiting cartilage-to-cartilage healing. The purpose of this study was to repopulate the induced ZCD through the combined effects of collagenase treatment and delivery of a chemotactic agent.


METHODS
In bovine cartilage, the ZCD induced by the OATS™ osteochondral harvesting system was determined, followed by a corresponding collagenase treatment to penetrate the developed ZCD. The chemotactic potential of platelet derived growth factor (PDGF-bb), insulin-like growth factor I (IGF-I), and basic fibroblast growth factor (bFGF) (2.5-100 ng/mL) was then assessed using a modified Boyden chamber assay to select an appropriate agent to induce chondrocyte migration. Afterwards, the combined effects of collagenase treatment and chondrocyte chemotaxis on the repopulation of an induced ZCD were examined in cartilage explants over a 4-week-period.


RESULTS
The OATS™ osteochondral harvesting system induced a significant ZCD (173 μm, 95% CI: [72-274 μm]) in the grafts. Chondrocyte chemotaxis was induced by all agents investigated at concentrations greater than 25 ng/mL. After 4 weeks in culture, collagenase treatment alone reduced the ZCD by approximately 40% relative to untreated explants. Coupling the collagenase treatment with 25 ng/mL IGF-I reduced the ZCD by approximately 80% relative to untreated explants, and 65% relative to explants treated only with collagenase.


CONCLUSIONS
Treating cartilage explants with collagenase and 25 ng/mL IGF-I resulted in a decreased ZCD after a 4-week-period, and increased chondrocyte density within the induced ZCD.
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada.
A J
AJ
McGregor
B G
BG
Amsden
S D
SD
Waldman
D000818:Animals; D000077214:Becaplermin; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D019902:Chondrocytes / Q000187:drug effects / Q000502:physiology*; D015194:Diffusion Chambers, Culture; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D007334:Insulin-Like Growth Factor I