Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.

Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.

CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).

CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.

Aims

The aim of this study was to investigate the feasibility of application of a 3D-printed megaprosthesis with hemiarthroplasty design for defects of the distal humerus or proximal ulna following tumour resection.

With information about a patient's bone mechanical properties orthopaedic operations could be optimised to reduce intra- and post-operative complications. However, there is currently no reliable method of measuring a patient's bone mechanical properties in vivo. We have previously investigated microindentation, using a 1.5mm diameter spherical indenter tip, and found no correlation between these measurements and compression testing measurements. We hypothesised that by using a larger diameter indenter tip we would closer match bone millimetre-scale mechanical properties.

20 bone samples were taken from 20 patients undergoing hip replacement surgery. The samples were machined from the femoral neck calcar cortical bone into 6×3×3mm parallelepiped specimens, aligned with the osteons along the long axis. The samples were micro-computed tomography (CT) scanned to calculate porosity. Microindentation was performed using a 6mm diameter, sapphire, spherical indenter tip. 12 indentations were performed in a grid and the reduced moduli were calculated using the Oliver-Pharr method. Compression testing was then performed to failure and the apparent elastic modulus was calculated for each sample.

A moderate correlation was found between the indentation reduced moduli and compression testing elastic moduli (r=0.52, r2=0.275, p=0.018). In addition, a moderate correlation was found between the indentation reduced moduli and CT-measured porosity (r=0.5, r2=0.251, p=0.025) and a strong correlation was found between compression testing moduli and porosity (r=0.75, r2=0.568, p<0.001).

Using large-tip spherical microindentation, indentation reduced moduli correlated significantly with compression testing apparent elastic moduli in these 20 cortical bone specimens. Microindentation using a large, spherical indenter tip may predict the mechanical properties of bone at the millimetre length scale and shows promise as a potential future clinical decision aid in surgery.