Magnetic resonance imaging assessment of tissueengineering cartilage in vivo
In the current literature, most of the in vivo MRI studies of cartilage or osteochondral defect healing after a surgical procedure do not involve any scaffolding material [60-66]. Those studies are not included in this chapter. However, there are significant numbers of animal studies where a biocompatible polymer is included in the recovery and regeneration of a cartilage lesion in vivo. As stated earlier, T2 is the most commonly employed to observe the defect fill and assess the regenerated tissue. In addition to T2, the gadolinium-enhanced T1 and MT have been also used for the assessment of regenerated tissue in vivo [61,66]. A rabbit model is most commonly used for such studies because of cost effectiveness and because many biocompatible materials are still at the preclinical experimental stage of development. Goats and sheep have also been used with in vivo MRI studies of cartilage tissue engineering involving polymers.
When T2 is used for assessing defect fill in cartilage regeneration, it is shown to decrease with fill time and converge to the natural tissue surrounding the defect fill. For example, Ramaswamy et al. observed 5 weeks of healing for full thickness chondral defect using photopolymerized PEGDA in rabbit models and found that T2 decreases monotonically with the extent of defect bill (r = -0.82 between T2 and percent of defect fill) [67]. Recently, T2 was also used in a clinical study (n = 15) tnvolving cartilage regeneration using photopolymerized PEGDA applied after standard microfracture surgery [68]. The mean T2 was seen to decrease over the period of 6 months, suggesting better cartilage healing in biomaterial-based recovery compared to the cases where no biomaterial was involved. However, in some cases, T2 does not seem to change with time, even though the defect fill shows normal progression. For example, Kim et al. created a 3 mm osteochondral defect in rabbits and filled it with thrombin peptide (TP-508) and PLGA microspheres [69]. Their repair tissue had significantly higher T2 than the natural cartilage after 6 weeks and was similar to the control PLGA microspheres alone. Here we suspect that T2 values are influenced by scaffold contribution rather than the contribution from the growing matrix [14,52]. In our publication, we have shown that once the scaffold contribution is removed, the T2 values reflect the amount of tissue growth in vivo [70]. The advantages of using T2 for cartilage tissue-engineering assessment in vivo are (a) easier implementation for experimental protocol, (b) short acquisition time compared to most other MR parameter acquisition, and (c) sensitivity to detect small changes in defect fill areas. In natural cartilage, T2 is shown to be sensitive to the collagen orientation; however, in most cases, the engineered tissue is found to be less anisotropic, and therefore T2 reveals only the extent to which the defect is filled [11,14,71].
