TNF and osteoarthritis: Based on our previous findings, demonstrating that 10 and 50 ng/mL TSG-6 suppressed TNF-α secretion from macrophages in vitro (19), and supported by extensive literature research, showing that 50 μg TSG-6 exerts immunomodulatory and pro-regenerative effects in rodent models of osteoarthritis (18), traumatic brain injury (16), and severe burn wounds (36), we conducted a pilot study to define the optimal dose for fracture healing.