Biomaterials. 2015 Apr;47C:29-40. doi: 10.1016/j.biomaterials.2014.12.014. Epub 2015 Feb 2.

Reengineering autologous bone grafts with the stem cell activator WNT3A.

Jing W¹, Smith AA¹, Liu B¹, Li J¹, Hunter DJ¹, Dhamdhere G¹, Salmon B², Jiang J³, Cheng D¹, Johnson CA¹, Chen S¹, Lee K¹, Singh G¹, Helms JA¹.

Abstract

Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stemcells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly.