The most critical factor for fracture union is the blood supply to the fracture site, which is usually impaired in patients with diabetes. Recently, mesenchymal stem cells-derived conditioned medium (MSC-CM) has shown significantly higher levels of angiogenic factors, such as VEGF and IL-6. We demonstrate in this report that MSC-CM delivered in gelatin sponges stimulates angiogenesis and promotes fracture healing in a diabetic rat model. Subcutaneous implantation of gelatin sponges soaked in MSC-CM demonstrated better tissue ingrowth and higher capillary densities at 2 and 3 weeks than gelatin sponges in minimal essential medium (MEM) or 293 cell-derived conditioned medium (293-CM). Implantation of fibular defects with gelatin sponges soaked in MSC-CM enhanced bone ingrowth and fracture healing rates compared to 293-CM and MEM groups at 8 weeks. Micro-computed tomography analysis further indicated a higher new bone volume in the MSC-CM group compared to the other diabetic groups. Histological analysis with CD31 immunostaining also revealed that MSC-CM increased endothelial cell counts compared to the other groups. Together, these results indicated that gelatin sponges used to deliver MSC-CM promote angiogenesis and fracture healing in a diabetic model and may be an alternative strategy for treating fracture non-union in patients with diabetes.
Copyright © 2011 John Wiley & Sons, Ltd.