Combination of Heel-strike like Mechanical Loading with Deproteinized Cancellous Bone Scaffold Implantation to Repair Segmental Bone Defects in Rabbits.

Under physiological conditions bone defects often occur at mechanical load bearing sites and bone substitutes used for regeneration should be similarly subjected to mechanical loading stress. In this study, we investigated whether a novel heel-strike like mechanical loading method can be used as a complementary therapy to promote bone regeneration following bone substitute grafting. To test this, three groups of rabbits with segmental bone defects in the tibia were implanted with bovine deproteinized cancellous bone scaffold (DCBS), with one group also receiving heel-strike like mechanical loading generated by a rap stress stimulator. From weeks 4-12 post-operation X-ray and micro-CT scanning showed that rabbits receiving combination therapy had significantly more callus at the bone defect. Moreover, bone defects in the combination group were completely replaced with new bone at week 12, while the DCBS implantation alone group healed only partially and rabbits receiving neither DCBS nor mechanical loading developed only small calluses throughout the observation period. Analysis of micro-CT scanning results demonstrated that new bone density in the combination group was significantly higher than the DCBS only group at weeks 4 and 12 (p<0.05). H&E staining results also indicated a significantly higher percentage of new bone in the bone defect area and a lower percentage of residual scaffold in the combination group compared to the DCBS only group (p<0.05). Thus, this heel-strike like mechanical loading method appears to accelerate bone regeneration following substitute implantation by restoring a local mechanical loading environment in segmental bone defects.

A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.

We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects.

Factors affecting the evacuation rate of intracerebral hemorrhage in basal ganglia treated by minimally invasive craniopuncture.

OBJECTIVE: Minimally invasive craniopuncture has been used to treat intracerebral hemorrhage (ICH) for over 20 years in China. However, one-off total evacuation of hematoma cannot be achieved through this procedure because it is not an open surgery. This study is designed to identify factors that can increase the hematoma evacuation rate (ER) of this procedure and to evaluate the influence of ER on long-term outcome. METHODS: A total of 309 patients with basal ganglia ICH treated by minimally invasive craniopuncture were analyzed retrospectively. Univariate and multivariate linear regression analyses were used to identify factors correlated with a high ER. The correlation between ER and long-term outcome was also analyzed by logistic regression and the Spearman correlation. RESULTS: A low hematoma mean CT number (ß=-0.773, p<0.001) and postoperative cerebrospinal fluid (CSF) outflow (ß=0.193, p<0.001) were found to be independent factors associated with a high ER. In patients with 30-50ml of hematoma, a high ER was correlated with a high Barthel index improvement (r=0.611, p<0.001) and a high modified Rankin scale decline (r=0.517, p<0.001). In patients with 50-80ml of hematoma, a high ER was a protective factor of case fatality (B=-2.297, p=0.005). CONCLUSIONS: The hematoma mean CT number can predict the efficiency of minimally invasive craniopuncture in patients with ICH. In patients with ventricular involvement, the tip of the puncture needle should be placed close to the tear in the ventricle rather than at the center of the hematoma to facilitate postoperative CSF outflow.