3. Biodistribution of needle-injections and needle-free jet-injections visualized by a 3D- Fluorescent Imaging Cryomicrotome System 85 3. DISCUSSION To date, studies about the treatment of keloids have focused on the various drugs for intralesional administration while the challenges and limitations of optimal biodistribution in keloids have been neglected. In this exploratory study, the 3D biodistribution of TCA using different drug delivery techniques in ex vivo keloids and normal skin was assessed using the 3D-FICS. Large heterogeneity in TCA volumes was observed in keloids. This may be the result of the large variation in mechanical properties such as rigidity and viscoelasticity among different keloids and even within the same keloid. This variation in mechanical properties may depend on the anatomic location, prior treatment and genetic predisposition (1, 3, 22). Moreover, with jet injectors the fluorescent TCA volume seems to be smaller compared to needle injections. This is in line with the large residual TCA volume remaining on the skin surface of keloids (71.9 µl ± 14.3) after jet injection. Pressures generated by the jet injector may not be sufficient for penetrating the recalcitrant solid keloids in this ex vivo setting. Notably, the considerable operator injection force as applied in the experiments with needle injection could only be possible in clinical practice if prior local anesthesia has been applied, as it could be very painful otherwise. And for jet injections, repeating the injection would preferably be performed in clinical practice if a high amount of residual fluid is observed directly after jet injection. For needle injections, blanching is an endpoint of infiltration in clinical setting. However, this could not be used as a reference in these experiments using ex vivo samples without blood perfusion. Compared to lower pressures, a higher pressure of 6 Bar seems to result in larger fluorescent TCA volumes in keloids. It should be emphasized that fluorescent TCA volumes are not equivalent to actual delivered TCA volumes. We assume that even though 6 Bar may result in larger fluorescent TCA distribution compared to lower pressures, the actual delivered TCA dose was lower, as reflected by the larger residual volumes. The reason for the latter is unclear; and the effect of different pressure levels on the biodistribution in keloids needs further investigation.
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