We previously demonstrated that the intravenous delivery of multipotent adult progenitor cells (MAPCs) after traumatic brain injury (TBI) in rodents provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment; however, the long-term behavioral and anti-inflammatory effects of MAPC administration after TBI have yet to be explored. We hypothesized that the intravenous injection of MAPCs after TBI attenuates the inflammatory response (as measured by microglial morphology) and improves performance at motor tasks and spatial learning (Morris water maze [MWM]). MAPCs were administered intravenously 2 and 24 hours after a cortical contusion injury (CCI). We tested four groups at 120 days after TBI: sham (uninjured), injured but not treated (CCI), and injured and treated with one of two concentrations of MAPCs, either 2 million cells per kilogram (CCI-2) or 10 million cells per kilogram (CCI-10). CCI-10 rats showed significant improvement in left hind limb deficit on the balance beam. On the fifth day of MWM trials, CCI-10 animals showed a significant decrease in both latency to platform and distance traveled compared with CCI. Probe trials revealed a significant decrease in proximity measure in CCI-10 compared with CCI, suggesting improved memory retrieval. Neuroinflammation was quantified by enumerating activated microglia in the ipsilateral hippocampus. We observed a significant decrease in the number of activated microglia in the dentate gyrus in CCI-10 compared with CCI. Our results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvements in spatial learning as well as attenuation of neuroinflammation. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:953-960

Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E2 (PGE2) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1-type activated microglia in the hippocampus. These results demonstrate that force provides critical cues to MSCs residing at the vascular interface which influence immunomodulatory and paracrine activity, and suggest the potential therapeutic use of force for MSC functional enhancement.

The injection of human and rat MSCs through various clinically relevant catheters and flow rates did not have a clinically significant effect on viability immediately after injection, indicating compliance with recently published Food and Drug Administration guidelines (viability >70%). Further, no changes in cell characterization or function were observed via measurement of cell surface markers and the capacity for multilineage differentiation, respectively. These results ensure the biocompatibility of MSCs with commonly used delivery methods.

We demonstrate the design of thin flexible pressure sensors based on piezoelectric PVDF-TrFE (polyvinyledenedifluoride-tetrafluoroethylene) co-polymer film, which can be integrated onto a catheter, where the compact inner lumen space limit the dimensions of the pressure sensors. Previously, we demonstrated that the thin-film sensors of one micrometer thickness were shown to have better performance compared to the thicker film with no additional electrical poling or mechanical stretching due to higher crystallinity. The pressure sensors can be mass producible using standard lithography process, with excellent control of film uniformity and thickness down to one micrometer. The fabricated pressure sensors were easily mountable on external surface of commercial catheters. Elaborate experiments were performed to demonstrate the applicability of PVDF sensors towards catheter based biomedical application. The resonant frequency of the PVDF sensor was found to be 6.34 MHz. The PVDF sensors can operate over a broad pressure range of 0-300 mmHg. The average sensitivity of the PVDF sensor was found to be four times higher (99 μV/mmHg) than commercial pressure sensor while the PVDF sensor (0.26 s) had fivefold shorter response time than commercial pressure sensor (1.30 s), making the PVDF sensors highly suitable for real-time pressure measurements using catheters.

BACKGROUND: 3D printing is an additive manufacturing process allowing the creation of solid objects directly from a digital file. We believe recent advances in additive manufacturing may be applicable to surgical instrument design. This study investigates the feasibility, design and fabrication process of usable 3D printed surgical instruments. METHODS: The computer aided design (CAD) package Solid Works (Dassault Systemes SolidWorks Corp., Waltham MA) was used to design a surgical set including hemostats, needle driver, scalpel handle, retractors and forceps. These designs were then printed on a selective laser sintering (SLS) Sinterstation HiQ (3D Systems, Rock Hill SC) using DuraForm EX Plastic. The final printed products were evaluated by practicing general surgeons for ergonomic functionality and performance, this included simulated surgery and inguinal hernia repairs on human cadavers. Improvements were identified and addressed by adjusting design and build metrics. RESULTS: Repeated manufacturing processes and redesigns led to the creation of multiple functional and fully reproducible surgical sets utilizing the user feedback of surgeons. Iterative cycles including design, production and testing took an average of 3 days. Each surgical set was built using the SLS Sinterstation HiQ with an average build time of 6 hours per set. CONCLUSIONS: Functional 3D printed surgical instruments are feasible. Advantages compared to traditional manufacturing methods include no increase in cost for increased complexity, accelerated design to production times and surgeon specific modifications.