Thymosin β 4 administration enhances fracture healing in mice

Thymosin β 4 (Tβ 4 ) is a regenerative peptide that we hypothesized would promote healing of fractured bone. Mice received a bilateral fibular osteotomy and were given i.p. injections of either Tβ 4 (6 mg/kg) or saline. Calluses from saline‐ and Tβ 4 ‐treated mice were analyzed for: (1) biomechanical properties and (2) composition using micro‐computed tomography (µCT) and histomorphometry. Biomechanical analysis showed that Tβ 4 ‐treated calluses had a 41% increase in peak force to failure ( p  < 0.01) and were approximately 25% stiffer ( p  < 0.05) than saline‐treated controls. µCT analysis at 21 days post‐fracture showed that the fractional volume of new mineralized tissue and new highly mineralized tissue were respectively 18% and 26% greater in calluses from Tβ 4 ‐treated mice compared to controls ( p  < 0.01; p  < 0.05, respectively). Histomorphometry complemented the µCT data; at 21 days post‐fracture, Tβ 4 ‐treated calluses were almost 23% smaller ( p  < 0.05), had nearly 47% less old cortical bone ( p  < 0.05) and had a 31% increase in new trabecular bone area/total callus area fraction compared with controls ( p  < 0.05). Our finding of enhanced biomechanical properties of fractures in mice treated with Tβ 4 provides novel evidence of the therapeutic potential of this peptide for treating bone fractures. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1277–1282, 2014.