Large molecule delivery to the growth plate increases with limb temperature measured by in vivo multiphoton imaging

Bone elongation occurs in cartilaginous growth plates, which rely on surrounding blood vessels for nutrition. New imaging modalities that enable real‐time study of vascular access to growth plates have potential to fundamentally advance understanding of physiological growth regulation. Our lab employs in vivo multiphoton microscopy to measure environmental effects on entrance of systemically‐introduced fluorescent tracers into tibial growth plates of 5 week old mice. We previously found temperature‐ and exercise‐related changes in small molecule delivery using the 332 Da tracer fluorescein. Here we test the hypothesis that warm peripheral temperature increases large molecule delivery to growth plates using 10 kDa dextrans that approximate the size of physiological factors such as IGF‐I, a potent growth stimulator. We immersed hindlimbs of mice in 22C or 37C Ringer's and kept core temperature constant. Large molecule entry into the growth plate was minimal at 22C and increased when the limb was warmed to 37C. Vessel diameter was increased at 37C, suggesting that heat enhances blood volume and bioavailability of large molecules around the growth plate. As our experimental temperatures were within ranges reported for human knee joints, these results are relevant to strategies for targeting delivery of therapeutic agents to growth plates of children. Supported by MU‐ADVANCE and NASA WV Space Grant Consortium.