Validation of a bioabsorbable device that seals perforations after Tuohy needle dural puncture in an ovine model.

BACKGROUND: We designed a device to close accidental dural puncture via the offending puncturing epidural needle directly after diagnosis of the puncture and before removing the needle. The aim of this study was to quantify this device's ability to seal cerebrospinal fluid leakage. METHODS: Forty-six anesthetized adult sheep were studied in a single-blind randomized controlled fashion in two equal groups.An intentional dural puncture was performed with an 18-gage Tuohy needle on all the sheep between L6 and S1 levels. Contrast medium was injected through the needle. Twenty-three animals receive treatment with the sealing device. Two minutes after device placement, or dural puncture in the control group, a CT scan was performed on the animals to estimate contrast material leakage. A region of interest (ROI) was defined as the region that enclosed the subarachnoid space, epidural space, and neuroforaminal canal (the vertebral body above and half of its equivalent height in sacrum below the puncture site). In this region, the total contrast volume and the volumes in the epidural space (EPIDURAL) were measured. The primary outcome measure was the EPIDURAL/ROI ratio to ascertain the proportion of intrathecally injected fluid that passed into the epidural space in both groups. The secondary outcomes were the total amount of contrast in the ROI and the EPIDURAL. RESULTS: The device was deployed successfully in all but two instances, where it suffered from manufacturing defects.Leakage was less in the study group (1.0 vs 1.4 mL, p=0.008). The median EPIDURAL/ROI ratio was likewise less in the study group (29 vs 46; p=0.013; 95% CI (-27 to -3.5)). CONCLUSION: This novel dural puncture-sealing device, also envisaged to be used in other comparable iatrogenic leakage scenarios to be identified in the future, was able to reduce the volume of cerebrospinal fluid that leaked into the epidural space after dural puncture. The device is possibly a valuable way of preventing fluid leakage immediately after the recognition of membrane puncture.

Action of recombinant human BMP-2 on fracture healing in rabbits is dependent on the mechanical environment.

The utility of recombinant human bone morphogenetic protein-2 (rhBMP-2) in inducing bone formation in fractures of bone is well known. However, the influence of the mechanical environment on the actions of rhBMP-2 on fracture healing is not clear. An experimental model of fractures of the tibia in rabbits was developed and utilized to investigate the role of mechanical environment on rhBMP-2 action. A 1 mm osteotomy gap was stabilized by either a low- or high-stiffness fixator (LSF or HSF, respectively), and local treatment with rhBMP-2 in an absorbable collagen sponge (ACS) was evaluated. The results of the investigation were analysed by both histomorphometry and biomechanics. The LSF caused an increase in mineralized periosteal callus compared to HSF, the rhBMP-2 in ACS accelerated fracture healing only in the LSF group but not in the HSF group. The area of mineralized tissue in interfragmentary callus was determined by fixation stiffness and not by BMP treatment. rhBMP-2 caused higher bone resorption in the endosteal callus during the late stages of fracture healing, but these histological differences did not affect the mechanical properties. Biomechanical evaluation showed only differences at 3 weeks between LSF-rhBMP-2 and LSF-ACS. The bending and torsional properties were higher in the rhBMP-2/ACS group compared to ACS alone at 3 weeks.

Activated spinal cord ependymal stem cells rescue neurological function.

Spinal cord injury (SCI) is a major cause of paralysis. Currently, there are no effective therapies to reverse this disabling condition. The presence of ependymal stem/progenitor cells (epSPCs) in the adult spinal cord suggests that endogenous stem cell-associated mechanisms might be exploited to repair spinal cord lesions. epSPC cells that proliferate after SCI are recruited by the injured zone, and can be modulated by innate and adaptive immune responses. Here we demonstrate that when epSPCs are cultured from rats with a SCI (ependymal stem/progenitor cells injury [epSPCi]), these cells proliferate 10 times faster in vitro than epSPC derived from control animals and display enhanced self renewal. Genetic profile analysis revealed an important influence of inflammation on signaling pathways in epSPCi after injury, including the upregulation of Jak/Stat and mitogen activated protein kinase pathways. Although neurospheres derived from either epSPCs or epSPCi differentiated efficiently to oligodendrocites and functional spinal motoneurons, a better yield of differentiated cells was consistently obtained from epSPCi cultures. Acute transplantation of undifferentiated epSPCi or the resulting oligodendrocyte precursor cells into a rat model of severe spinal cord contusion produced a significant recovery of motor activity 1 week after injury. These transplanted cells migrated long distances from the rostral and caudal regions of the transplant to the neurofilament-labeled axons in and around the lesion zone. Our findings demonstrate that modulation of endogenous epSPCs represents a viable cell-based strategy for restoring neuronal dysfunction in patients with spinal cord damage.