Objective
Bone regeneration disorders can be a critical issue in patients with diabetes mellitus. Adipose-derived stem cells (ASCs) are deemed as one of the ideal sources for cell therapy, but their healing potential may be hindered in a diabetic milieu. The aim of this study is to investigate the osteogenic potential of diabetic ASCs and their treatment effect after addition of Wnt-3a as a cell pretreatment method.

Material and Methods
ASCs are retrieved from diabetic mice models induced by a high-fat diet plus streptozocin. Cell metabolic activity, alkaline phosphatase (ALP) activity, mineralization, and osteogenic gene expression are evaluated. A biomimetic scaffold containing cryogel and ASCs is utilized to assess the impact of a diabetic condition and the cell pretreatment effect of Wnt-3a both in vitro and in vivo.

Results
ASCs from diabetic mice showed impaired ALP activity and calcium deposition. They also showed impeded activation of Wnt signaling pathway by lowered expression of CTNNB1. The addition of Wnt-3a to the osteogenesis differential medium can partially revive the osteogenic potential of diabetic ASCs, as shown by elevated expression of CTNNB1, RUNX2, ALP, and COL1A1. Their improved bone healing capability is also confirmed in an in vivo mice model.

Conclusions
Diabetic ASCs have impaired bone healing capability due to their worse osteogenesis, and our study showed that addition of Wnt-3a to the osteogenesis differentiation medium may rescue their bone regeneration potential. This finding offers a potential clinical strategy for enhancing bone healing in patients suffering from diabetic osteoporosis.

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