Systemic Administration of PTH Supports Vascularization in Segmental Bone Defects Filled with Ceramic-Based Bone Graft Substitute.

Non-unions continue to present a challenge to trauma surgeons, as current treatment options are limited, duration of treatment is long, and the outcome often unsatisfactory. Additionally, standard treatment with autologous bone grafts is associated with comorbidity at the donor site. Therefore, alternatives to autologous bone grafts and further therapeutic strategies to improve on the outcome and reduce cost for care providers are desirable. In this study in Sprague-Dawley rats we employed a recently established sequential defect model, which provides a platform to test new potential therapeutic strategies on non-unions while gaining mechanistic insight into their actions. The effects of a combinatorial treatment of a bone graft substitute (HACaS+G) implantation and systemic PTH administration was assessed by µ-CT, histological analysis, and bio-mechanical testing and compared to monotreatment and controls. Although neither PTH alone nor the combination of a bone graft substitute and PTH led to the formation of a stable union, our data demonstrate a clear osteoinductive and osteoconductive effect of the bone graft substitute. Additionally, PTH administration was shown to induce vascularization, both as a single adjuvant treatment and in combination with the bone graft substitute. Thus, systemic PTH administration is a potential synergistic co-treatment to bone graft substitutes.

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier.

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m2/g) were compared with beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2x10(5) expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 416 MSC/CDHA composites compared to 216 MSC/beta-TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls (p<0.001). Furthermore, ALP was significantly (p<0.05) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to beta-TCP blocks.