“…However, exposure to prolonged culture in hypoxic conditions ( > 1 week), thus, mimicking an ischemic dermal environment, did not support these processes. 112 Similarly, other studies using dermal fibroblasts have reported up-regulated expression of pro-a1 (I) 113 and (III) collagens 114,115 after acute exposure to hypoxic conditions in vitro, followed by decreased expression in response to prolonged hypoxia. 114,115 Under hypoxic conditions dermal fibroblastproduced collagen cannot be synthesized or crosslinked effectively, since the enzymes required for collagen polymerization and crosslinking, prolyl hydroxylase, lysyl hydroxylase, and lysyl oxidase, all require molecular oxygen as a cofactor to perform their biological function in the collagen synthesis and maturation pathway.…”