A hepatic scaffold from decellularized liver tissue: Food for thought

Allogeneic liver transplantation is still deemed the gold standard solution for end-stage organ failure; however, donor organ shortages have led to extended waiting lists for organ transplants. In order to overcome the lack of donors, the development of new therapeutic options is mandatory. In the last several years, organ bioengineering has been extensively explored to provide transplantable tissues or whole organs with the final goal of creating a three-dimensional growth microenvironment mimicking the native structure. It has been frequently reported that an extracellular matrix-based scaffold offers a structural support and important biological molecules that could help cellular proliferation during the recellularization process. The aim of the present review is to underline the recent developments in cell-on-scaffold technology for liver bioengineering, taking into account: (1) biological and synthetic scaffolds; (2) animal and human tissue decellularization; (3) scaffold recellularization; (4) 3D bioprinting; and (5) organoid technology. Future possible clinical applications in regenerative medicine for liver tissue engineering and for drug testing were underlined and dissected

Eccentricity signal in the nannofossil time-series across the Mid-Pleistocene Transition in the northwestern Pacific Ocean (ODP Site 1209)

The Mid-Pleistocene Transition (MPT; 1.25–0.6 million years ago, Ma) is one of the most important and still debated climate reorganizations during which the glacial/interglacial cycles switched from a 41-thousand years (kyr) cycle (i.e. obliquity) to a quasi-periodic 100-kyr cycle (associated with orbital eccentricity). Variations in the orbital geometry can affect the abundance and distribution of certain marine biota such as the coccolithophores, a group of unicellular calcifying phytoplankton, whose skeletal remains – called nannofossils – represent a valid tool within the geological archives to infer change in surface water conditions and/or coccolithophore productivity and how orbital variations may have impacted them. Here, we apply for the first time various time series analytical techniques to the nannofossil dataset from mid-latitudinal Ocean Drilling Program (ODP) Site 1209 in the northwest Pacific Ocean for the interval spanning the last 1.6 Myr. To better interpret the orbital signal recorded by different nannofossil species we used time series analyses (i.e. wavelet, autocorrelation and cross correlation) to identify the main periodicities by single nannofossil species during the MPT, and to investigate further their response timings to those orbital drivers. In addition, we investigated how the recorded periodicities can improve understanding of the paleoecological preferences of particular species. The combination of multiple time series analyses allowed identification of the 100-kyr periodicity as the main cyclicity recorded in most analyzed species at Site 1209, documenting the predominance of the eccentricity-related signal at mid-latitudes and a reduced or absent influence of the obliquity response. Thus, our data highlight how orbital influence varies by latitude impacting the nannofossil species. The lag between eccentricity and species abundance fluctuations was also investigated, identifying a fast response ranging between 20 and 40 kyr for the taxa Calcidiscus leptoporus subspecies leptoporus, Gephyrocapsa caribbeanica small, and Reticulofenestra spp. (>5 μm). This study corroborates the potential of nannofossils to deepen understanding of the dynamics and effects of variations in orbital geometry through time. It also underlines the need to extend the study of the responses of specific species through the use of different time series analysis techniques in order to return complementary information and detect clearer orbital signals

Tubulization with chitosan guides for the repair of long gap peripheral nerve injury in the rat

Biosynthetic guides can be an alternative to nerve grafts for reconstructing severely injured peripheral nerves. The aim of this study was to evaluate the regenerative capability of chitosan tubes to bridge critical nerve gaps (15 mm long) in the rat sciatic nerve compared with silicone (SIL) tubes and nerve autografts (AGs). A total of 28 Wistar Hannover rats were randomly distributed into four groups (n = 7 each), in which the nerve was repaired by SIL tube, chitosan guides of low (∼2%, DAI) and medium (∼5%, DAII) degree of acetylation, and AG. Electrophysiological and algesimetry tests were performed serially along 4 months follow-up, and histomorphometric analysis was performed at the end of the study. Both groups with chitosan tubes showed similar degree of functional recovery, and similar number of myelinated nerve fibers at mid tube after 4 months of implantation. The results with chitosan tubes were significantly better compared to SIL tubes (P < 0.01), but lower than with AG (P < 0.01). In contrast to AG, in which all the rats had effective regeneration and target reinnervation, chitosan tubes from DAI and DAII achieved 43 and 57% success, respectively, whereas regeneration failed in all the animals repaired with SIL tubes. This study suggests that chitosan guides are promising conduits to construct artificial nerve grafts

Revealing the therapeutic potential of botulinum neurotoxin type a in counteracting paralysis and neuropathic pain in spinally injured mice

Botulinum neurotoxin type A (BoNT/A) is a major therapeutic agent that has been proven to be a successful treatment for different neurological disorders, with emerging novel therapeutic indications each year. BoNT/A exerts its action by blocking SNARE complex formation and vesicle release through the specific cleavage of SNAP-25 protein; the toxin is able to block the release of pro-inflammatory molecules for months after its administration. Here we demonstrate the extraordinary capacity of BoNT/A to neutralize the complete paralysis and pain insensitivity induced in a murine model of severe spinal cord injury (SCI). We show that the toxin, spinally administered within one hour from spinal trauma, exerts a long-lasting proteolytic action, up to 60 days after its administration, and induces a complete recovery of muscle and motor function. BoNT/A modulates SCI-induced neuroglia hyperreactivity, facilitating axonal restoration, and preventing secondary cells death and damage. Moreover, we demonstrate that BoNT/A affects SCI-induced neuropathic pain after moderate spinal contusion, confirming its anti-nociceptive action in this kind of pain, as well. Our results provide the intriguing and real possibility to identify in BoNT/A a therapeutic tool in counteracting SCI-induced detrimental effects. Because of the well-documented BoNT/A pharmacology, safety, and toxicity, these findings strongly encourage clinical translation

Doctor@Home: Through a Telemedicine Co-production and Co-learning Journey

Telemedicine and remote visits are becoming more and more popular in several medical disciplines, including oncology. The Covid-19 pandemic has enhanced the need to continue to meet patients’ ambulatory care necessities ensuring social distancing and limiting the access to clinical facilities. The National Cancer Institute of Aviano, Italy, has recently launched a program called “Doctor @ Home” (D@H). The pillars of the program are the co-production of the oncological care and the co-learning approach, which sees the clinical staff “hand in hand” with patients to maximize the outcome of the care, trying to take advantage of the new tools offered by modern technologies

Shared decision-making in trauma and emergency surgery settings. A literature review

Emergency teams are made up of professionals of different specialities, including emergency physicians, surgeons, anesthesiologists, and nurses. Such units are characterized by the need to face unexpected situations with little time to make clinical decisions. In trauma and emergency settings, clinicians must act in a coordinated way, ensuring, at the same time, proper knowledge transfer and sharing to reach the best possible result for the patient. While such dynamics must be explicit and clear within the team, involving the patient in the decision-making process may require additional tools and procedures. Indeed, the time to engage with the patient and the family to understand the patient’s wishes and treatment preferences may be limited or absent at all. While the so-called shared decision-making (SDM) stands as one of the pillars of the modern patient-centric healthcare scenario, knowledge translation and transfer dynamics may appear particularly challenging in emergency settings. Starting from an investigation of the recent literature on SDM, the paper presents a literature review of the barriers, facilitators, and knowledge translation dynamics of SDM in trauma and emergency surgery. Results assess the importance, tools, and dynamics of SDM processes

Image-Guided Surgical e-Learning in the Post-COVID-19 Pandemic Era: What Is Next?

The current unprecedented coronavirus 2019 (COVID-19) crisis has accelerated and enhanced e-learning solutions. During the so-called transition phase, efforts were made to reorganize surgical services, reschedule elective surgical procedures, surgical research, academic education, and careers to optimize results. The intention to switch to e-learning medical education is not a new concern. However, the current crisis triggered an alarm to accelerate the transition. Efforts to consider e-learning as a teaching and training method for medical education have proven to be efficient. For image-guided therapies, the challenge requires more effort since surgical skills training is combined with image interpretation training, thus the challenge is to cover quality educational content with a balanced combination of blended courses (online/onsite). Several e-resources are currently available in the surgical scenario; however, further efforts to enhance the current system are required by accelerating the creation of new learning solutions to optimize complex surgical education needs in the current disrupted environment

Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats

BACKGROUND: Autograft is still the gold standard technique for the repair of long peripheral nerve injuries. The addition of biologically active scaffolds into the lumen of conduits to mimic the endoneurium of peripheral nerves may increase the final outcome of artificial nerve devices. Furthermore, the control of the orientation of the collagen fibers may provide some longitudinal guidance architecture providing a higher level of mesoscale tissue structure. OBJECTIVE: To evaluate the regenerative capabilities of chitosan conduits enriched with extracellular matrix-based scaffolds to bridge a critical gap of 15 mm in the rat sciatic nerve. METHODS: The right sciatic nerve of female Wistar Hannover rats was repaired with chitosan tubes functionalized with extracellular matrix-based scaffolds fully hydrated or stabilized and rolled to bridge a 15 mm nerve gap. Recovery was evaluated by means of electrophysiology and algesimetry tests and histological analysis 4 months after injury. RESULTS: Stabilized constructs enhanced the success of regeneration compared with fully hydrated scaffolds. Moreover, fibronectin-enriched scaffolds increased muscle reinnervation and number of myelinated fibers compared with laminin-enriched constructs. CONCLUSION: A mixed combination of collagen and fibronectin may be a promising internal filler for neural conduits for the repair of peripheral nerve injuries, and their stabilization may increase the quality of regeneration over long gaps

Low-temperature anomalies in muon spin relaxation of solid and hollow nanoparticles: a pathway to detect unusual local spin dynamics

By means of muon spin relaxation measurements we unraveled the temperature spin dynamics in monodisperse maghemite spherical nanoparticles with different surface to volume ratio, in two samples with a full core (diameter D∼4 and D∼5nm) and one with a hollow core (external diameter D∼7.4nm). The behavior of the muon longitudinal relaxation rates as a function of temperature allowed us to identify two distinct spin dynamics. The first is well witnessed by the presence of a characteristic peak for all the samples around the so-called muon blocking temperature T$_{B}^{μ+}$. A Bloembergen-Purcell-Pound (BPP)-like model reproduces the experimental data around the peak and at higher temperatures (20<T<100K) by assuming the Néel reversal time of the magnetization as the dominating correlation time. An additional dynamic emerges in the samples with higher surface to volume ratio, namely, full 4 nm and hollow samples. This is witnessed by a shoulder of the main peak for T<20K at low longitudinal field (μ$_{0}$H≈15mT), followed by an abrupt increase of the relaxation rate at T<10K, which is more evident for the hollow sample. These unusual anomalies of the longitudinal relaxation rate for T<T$_{B}^{μ+}$ are suggested to be due to the surface spins’ dynamical behavior. Furthermore, for weak applied longitudinal magnetic field (μ$_{0}$H≈15mT) and T<T$_{B}^{μ+}$ we observed damped coherent oscillations of the muon asymmetry, which are a signature of a quasistatic local field at the muon site as probed by muons implanted in the inner magnetic core of the nanoparticles. The muon spin relaxation technique turns out to be very successful to study the magnetic behavior of maghemite nanoparticles and to detect their unusual local spin dynamics in low magnetic field conditions