Evaluation of early osteochondral defect repair in a rabbit model utilizing fourier transform-infrared imaging spectroscopy, magnetic resonance imaging, and quantitative T2 mapping.
BACKGROUND
Evaluation of the morphology and matrix composition of repair cartilage is a critical step toward understanding the natural history of cartilage repair and efficacy of potential therapeutics. In the current study, short-term articular cartilage repair (3 and 6 weeks) was evaluated in a rabbit osteochondral defect model treated with thrombin peptide (TP-508) using magnetic resonance imaging (MRI), quantitative T2 mapping, and Fourier transform-infrared imaging spectroscopy (FT-IRIS).


METHODS
Three-mm-diameter osteochondral defects were made in the rabbit trochlear groove and filled with either TP-508 plus poly-lactoglycolidic acid microspheres or poly-lactoglycolidic acid microspheres alone (placebo). Repair tissue and adjacent normal cartilage were evaluated at 3 and 6 weeks postdefect creation. Intact knees were evaluated by magnetic resonance imaging for repair morphology, and with quantitative T2 mapping to assess collagen orientation. Histological sections were evaluated by FT-IRIS for parameters that reflect collagen quantity and quality, as well as proteoglycan (PG) content.


CONCLUSIONS
There was no significant difference in volume of repair tissue at either time point. At 6 weeks, placebo repair tissue demonstrated longer T2 values (p < 0.01) than TP-508 did. Although both placebo and TP-508 repair tissue demonstrated longer T2 values than adjacent normal cartilage did, the 6-week T2 values of the TP-508 specimens were closer to those of the adjacent normal cartilage than were the placebo values. FT-IRIS analysis demonstrated a significant increase in collagen content, integrity, and PG content of the TP-508 repair tissue from 3 to 6 weeks (p < or = 0.05). In addition, the collagen and PG content of the TP-508 samples were closer to normal cartilage at 3 weeks than were the placebo samples. Further, there was a significant inverse correlation between the T2 relaxation values and collagen orientation in the normal cartilage. However, there were no significant correlations between T2 relaxation values and any FT-IRIS parameter in the repair tissue. Together, the data demonstrate that MRI and FT-IRIS assessment of cartilage repair tissue provide molecular information that furthers understanding of the cartilage repair process.
Kim
Minwook
M
Hospital for Special Surgery, New York, NY, USA.
Foo
Li F
LF
Uggen
Christopher
C
Lyman
Steven
S
Ryaby
James T
JT
Moynihan
Daniel P
DP
Grande
Daniel Anthony
DA
Potter
Hollis G
HG
Pleshko
Nancy
N
D000818:Animals; D002358:Cartilage, Articular / Q000002:abnormalities* / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid; D008279:Magnetic Resonance Imaging; D008863:Microspheres; D023421:Models, Animal; D010446:Peptide Fragments / Q000494:pharmacology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D013917:Thrombin / Q000494:pharmacology
D010446:Peptide Fragments; D011509:Proteoglycans; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C412222:rusalatide acetate; D013917:Thrombin