Intraoperative manufacturing of patient specific instrumentation for shoulder arthroplasty: a novel mechatronic approach

Optimal orthopaedic implant placement is a major contributing factor to the long term success of all common joint arthroplasty procedures. Devices such as three-dimensional (3D) printed, bespoke guides and orthopaedic robots are extensively described in the literature and have been shown to enhance prosthesis placement accuracy. These technologies, however, have significant drawbacks, such as logistical and temporal inefficiency, high cost, cumbersome nature and difficult theatre integration. A new technology for the rapid intraoperative production of patient specific instrumentation, which overcomes many of the disadvantages of existing technologies, is presented here. The technology comprises a reusable table side machine, bespoke software and a disposable element comprising a region of standard geometry and a body of mouldable material. Anatomical data from Computed Tomography (CT) scans of 10 human scapulae was collected and, in each case, the optimal glenoid guidewire position was digitally planned and recorded. The achieved accuracy compared to the preoperative bespoke plan was measured in all glenoids, from both a conventional group and a guided group. The technology was successfully able to intraoperatively produce sterile, patient specific guides according to a pre-operative plan in 5 minutes, with no additional manufacturing required prior to surgery. Additionally, the average guide wire placement accuracy was 1.58 mm and 6.82◦ degrees in the manual group, and 0.55 mm and 1.76◦ degrees in the guided group, also demonstrating a statistically significant improvement

Sustained axon regeneration induced by co-deletion of PTEN and SOCS3

A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around 2 weeks after the crush injury. Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery

Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells:Comparison with human bone marrow and adipose-derived mesenchymal stem cells

We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair

Axotomy induces axonogenesis in hippocampal neurons through STAT3

After axotomy of embryonic hippocampal neurons in vitro, some of the axotomized axons lose their identity, and new axons arise and grow. This axotomy-induced axonogenesis requires importin, suggesting that some injury-induced signals are transported via axons to elicit axonogenesis after axotomy. In this study, we show that STAT3 is activated in response to axotomy. Because STAT3 was co-immunoprecipitated with importin β in the axotomized neurons, we suggest that STAT3 is retrogradely transported as molecular cargo of importin α/β heterodimers. Indeed, inhibition of importin α binding with STAT3 resulted in the attenuation of axonogenesis. Silencing STAT3 blocked the axonogenesis, demonstrating that STAT3 is necessary for axotomy-induced axonogenesis. Furthermore, the overexpression of STAT3 enhanced axotomy-induced axonogenesis. Taken together, these results demonstrate that activation and retrograde transport of STAT3 in injured axons have key roles in the axotomy-induced axonogenesis of hippocampal neurons

On the characterization of the heterogeneous mechanical response of human brain tissue

The mechanical characterization of brain tissue is a complex task that scientists have tried to accomplish for over 50 years. The results in the literature often differ by orders of magnitude because of the lack of a standard testing protocol. Different testing conditions (including humidity, temperature, strain rate), the methodology adopted, and the variety of the species analysed are all potential sources of discrepancies in the measurements. In this work, we present a rigorous experimental investigation on the mechanical properties of human brain, covering both grey and white matter. The influence of testing conditions is also shown and thoroughly discussed. The material characterization performed is finally adopted to provide inputs to a mathematical formulation suitable for numerical simulations of brain deformation during surgical procedures.</p

Studio interculturale sullo stato dell\u2019umore; progetto di ricerca internazionale.

Il contributo illustra uno studio sullo stato dell'umore in relazione a situazioni di competizioni sportiva e di valutazione accademica. L'indagine \ue8 stata realizzata con studenti di due universit\ue0 ungheresi e di una inglese