Early diagnosis of heterotopic ossification with a NIR fluorescent probe by targeting type II collagen

Heterotopic ossification (HO) is a devastating sequela in which the pathologic extracellular matrix of the cartilage and bone forms abnormally in soft tissues following traumatic injuries or orthopaedic surgeries. Early treatment is essential for inhibiting the progression of HO but is currently limited by the absence of sensitive and specific early diagnosis. Herein, this study exploits the enrichment of type II collagen (Col2a1) in the HO cartilage formation stage towards developing a near-infrared (NIR) probe for early HO diagnosis, namely WL-808 by conjugating a Col2a1-binding peptide (WYRGRL) and a cyanine dye (IR-808). WL-808 exhibits high specificity for targeting the cartilage in vitro and in vivo with no apparent cytotoxicity. The NIR signal of WL-808 can be detected in the HO cartilage lesions as early as 1 week after injury when micro-CT cannot show any ectopic bone formation. Moreover, the probe is rarely distributed in the normal knee articular cartilage in vivo via the intravenous administration method. Taken together, WL-808 demonstrates great potential in early HO diagnosis under NIR imaging, facilitating early HO prophylaxis and treatment in the clinic. NIR imaging with WL-808 diagnoses the early heterotopic ossification that cannot be detected by micro-CT.