Correlation of CT imaging and histology to guide bone graft selection in scaphoid non-union surgery.

INTRODUCTION: For the treatment of scaphoid non-unions (SNU), different surgical techniques, including vascularized and non-vascularized bone grafts, are applied. Besides stability, vascularity, and the biological situation at the non-union site are important for healing and the appropriate choice of treatment. We assessed the healing potential of SNUs by histological parameters and compared it to CT parameters of bone structure and fracture location. Based on the results, we developed a CT classification and a treatment algorithm to impact graft selection in SNU surgery. PATIENTS AND METHODS: Preoperative 2D-CT reformations of 29 patients were analyzed for trabecular structure, sclerosis, and fragmentation of the proximal fragment. The fracture location was assessed on 3D-CT reconstructions and grouped in three zones depending on the potential blood supply. Samples were taken during surgery for histological evaluation. Histological parameters of bone healing were defined and a bone healing capacity score (BHC), reflecting histological bone viability, was calculated. CT findings were compared to BHC, age of SNU, and time to union. RESULTS: Cases with trabecular structure and without fragmentation showed a statistically significant higher BHC. Time to union was significantly faster if trabecular structure was present and sclerosis was absent. In intraarticular proximal pole non-unions, where no blood supply is assumed, the BHC was statistically significantly lower and time to union was longer compared to SNUs of the other locations. A statistically significant correlation between BHC and time to union was found in the proximal and distal fragment with higher BHC associated with faster healing. CONCLUSIONS: CT parameters of bone structure and fracture location can reflect histological healing capacity of SNUs. This can guide bone graft selection in SNU surgery.

Time-dependent changes in bone healing capacity of scaphoid fractures and non-unions.

The scaphoid is the most frequently fractured carpal bone and prone to non-union due to mechanical and biological factors. Whereas the importance of stability is well documented, the evaluation of biological activity is mostly limited to the assessment of vascularity. The purpose of this study was to select histological and immunocytochemical parameters that could be used to assess healing potential after scaphoid fractures and to correlate these findings with time intervals after fracture for the three parts of the scaphoid (distal, gap and proximal). Samples were taken during operative intervention in 33 patients with delayed or non-union of the scaphoid. Haematoxylin and Eosin (HE), Azan, Toluidine, von Kossa and Tartrate-resistant acid phosphatase (TRAP) staining were used to characterise the samples histologically. We determined distribution of collagen 1 and 2 by immunocytochemistry, and scanning electron microscopy (SEM) was used to investigate the ultrastructure. To analyse the samples, parameters for biological healing status were defined and grouped according to healing capacity in parameters with high, partial and little biological activity. These findings allowed scoring of biological healing capacity, and the ensuing results were correlated with different time intervals after fracture. The results showed reduced healing capacity over time, but not all parts of the scaphoid were affected in the same way. For the distal fragment, regression analysis showed a statistically significant correlation between summarised healing activity scores and time from initial fracture (r = -0.427, P = 0.026) and decreasing healing activity for the gap region (r = -0.339, P = 0.090). In contrast, the analyses of the proximal parts for all patients did not show a correlation (r = 0.008, P = 0.969) or a decrease in healing capacity, with reduced healing capacity already at early stages. The histological and immunocytochemical characterisation of scaphoid non-unions (SNUs) and the scoring of healing parameters make it possible to analyse the healing capacity of SNUs at certain time points. This information is important as it can assist the surgeon in the selection of the most appropriate SNU treatment.

Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells.

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) regulates cell proliferation and survival by extracellular interaction and inactivation of the growth factor IGF-I. Beyond that, IGF-independent actions mediated by intracellular IGFBP-3 including nuclear-IGFBP-3, have also been described. We here show, using both confocal and electron microscopy and cell fractionation, that the extracellular addition of IGFBP-3 to living cells results in rapid uptake and nuclear delivery of IGFBP-3, by yet partly unknown mechanisms. IGFBP-3 is internalized through a dynamin-dependent pathway, traffics through endocytic compartments and is finally delivered into the nucleus. We observed docking of IGFBP-3 containing structures to the nuclear envelope and found IGFBP-3 containing dot-like structures to permeate the nuclear envelope. In summary, our findings establish the pathway by which this tumor suppressor protein is delivered from extracellular space to the nucleus.