Spatiotemporal presentation of exogenous SDF-1 with PLGA nanoparticles modulates SDF-1/CXCR4 signaling axis in the rodent cortex.

Stromal cell-derived factor-1 (SDF-1) and its key receptor CXCR4 have been implicated in directing cellular recruitment for several pathological/disease conditions thus also gained considerable attention for regenerative medicine. One regenerative approach includes sustained release of SDF-1 to stimulate prolonged stem cell recruitment. However, the impact of SDF-1 sustained release on the endogenous SDF-1/CXCR4 signaling axis is largely unknown as auto-regulatory mechanisms typically dictate cytokine/receptor signaling. We hypothesize that spatiotemporal presentation of exogenous SDF-1 is a key factor in achieving long-term manipulation of endogenous SDF-1/CXCR4 signaling. Here in the present study, we sought to probe our hypothesis using a transgenic mouse model to contrast the spatial activation of endogenous SDF-1 and CXCR4 in response to exogenous SDF-1 injected in bolus or controlled release (PLGA nanoparticles) form in the adult rodent cortex. Our data suggests that the manner of SDF-1 presentation significantly affected initial CXCR4 cellular activation/recruitment despite having similar protein payloads over the first 24 h (∼30 ng for both bolus and sustained release groups). Yet, one week post-injection, this response was negligible. Therefore, the transient nature CXCR4 recruitment/activation in response to bolus or controlled release SDF-1 indicated that cytokine/receptor auto-regulatory mechanisms may demand more complex release profiles (i.e. delayed and/or pulsed release) to achieve sustained cellular response.

A novel end-effector design for robotics in image-guided needle procedures.

BACKGROUND: Robotic end-effectors are being developed to facilitate image-guided minimally invasive needle-based procedures, such as tumour ablation, biopsy, thoracentesis and blood sampling. METHODS: A novel mechanical end-effector was designed to address the challenges associated with any major needle-based procedure, focusing on liver biopsy and ablation. In this end-effector embodiment, the distal end of a single articulating arm can grip needles and instruments and allows a fairly high number of degrees of freedom of movement during the complex motions associated with positioning and driving needles, as well as the periodic motions associated with breathing patterns. Tightening a cable that runs through the articulations fixes the arm in a rigid state, allowing insertion of the gripped needle. RESULTS: A design is presented that will require electro-mechanical stimulation and remote joystick control. The associated forces of cranial-caudal motion of soft tissue organs affects design constraints. A simulation study defined the process with tissue phantoms with mechanical properties in the range of hepatic tissue and the overlying abdominal wall. The robotic arm coupled with our end-effector could be deployed in an image-guided interventional suite. CONCLUSIONS: Such a switch-able and flexible mode for a robotic arm could overcome much of the current limitations for automated needle placements for mobile targets, and could mitigate risks from breathing or patient motion with a rigid needle gripper in place.