Bioengineering the Pancreas: Cell-on-Scaffold Technology

Nowadays, type I diabetes mellitus is a pathology afflicting millions of people globally with a dramatic assessment in the next future. Current treatments including exogenous insulin, pancreas transplantation and islets transplantation, are not free from important lifelong side effects. In the last decade, tissue engineering and regenerative medicine have shown encouraging results about the possibility to produce a functional bioengineered pancreas. Among many technologies, decellularization offers the opportunity to produce an organ-specific acellular matrix that could subsequently repopulate with endocrine cellular population. Herein, we aim to review the state-of-art and this technology highlighting the diabetes burden for the healthcare system and the major achievements toward the manufacturing of a bioengineered pancreas obtained by cell-on-scaffold technology

FPGA-based Low-Latency Audio Coprocessor for Networked Music Performance

Networked Music Performance (NMP) applications are acknowledged to be a particularly challenging field due to their stringent latency requirements and their demand for high audio quality. Most solutions developed in the last decades tried to overcome these obstacles by leveraging software approaches, that can introduce excessive time delays as a consequence of the general-purpose nature of the architectures on which they are implemented. Alternatively, a dedicated audio processor can be employed to minimize the mouth-to-ear latency.This paper presents the ongoing development of an hardware system that exploits an Application-Specific Instruction set Processor (ASIP) implemented on a Field-Programmable Gate Array (FPGA) to accelerate audio sample management. Specifically, a Transport Triggered Architecture (TTA) is being investigated as a processor design that aligns well with the required application domains. Preliminary empirical results indicate that the proposed solution has the potential to achieve extremely low latency, compatible with NMP requirements. Further optimizations and enhancements are actively being pursued to address the yet open challenges posed by NMP applications

Actuation and Control of a Steerable Catheter for Mitral Valve Repair

In the field of Structural Heart Diseases, Mitral Regurgitation's incidence is rising because of an aging population worldwide, and it has reached an annual mortality rate near 34%. The procedures of Structural Intervention Cardiology have enlarged the number of treated patients, since their minimally invasive and trans-catheter approach. To provide a forward step-change in this procedure, the aim of this work is to improve the use of the commercially available MitraClip system®, suggesting an innovative robot-assisted platform with autonomous control for the aforementioned system. The presented methodology is constituted of two phases: in the first one, we design, in the Solidworks® environment, 3D print and integrate the mechanical support with electrical motors and micro-controller devoted to catheter's steering. In the second phase, we develop the closed-loop position control to improve the accuracy in the autonomous positioning of the catheter. The described approach was tested to demonstrate its feasibility and dexterity: a position accuracy of 1.1±0.54 mm in following a given optimal trajectory was obtained

From micro- to nanostructured implantable device for local anesthetic delivery

Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release

Photodynamic therapy associated with full-mouth ultrasonic debridement in the treatment of severe chronic periodontitis: a randomized-controlled clinical trial

Background: Photodynamic therapy (PDT) is a method of microbial reduction which can benefit periodontal treatment in areas of difficult access, such as deep pockets and furcations. The aim of this randomized controlled clinical trial was to evaluate the effects of PDT as an adjunct to full-mouth ultrasonic debridement in the treatment of severe chronic periodontitis. Material and Methods: Twenty-two patients with at least one pocket with a probing depth (PD) of ≥7 mm and one pocket with a PD of ≥5 mm and bleeding on probing (BOP) on each side of the mouth were included, characterizing a split mouth design. The control group underwent full-mouth ultrasonic debridement and the test group received the same treatment associated with PDT. The PDT was performed on only one side of the mouth and the initial step consisted of subgingival irrigation with 0.005% methylene blue dye. Two minutes after applying the photosensitizer, the low power laser – AsGaAl (Photon Lase III – PL7336, DMC, São Carlos -São Paulo, Brazil) was applied (660 nm, 100 mW, 9 J, 90 seconds per site, 320 J/cm 2 , diameter tip 600 µm). The following clinical parameters were evaluated: plaque index, gingival index, BOP, gingival recession (GR), PD, and clinical attachment level (CAL). All parameters were collected before, 1, 3 and 6 months after treatment. Results: An improvement in BOP, PD and CAL was observed after treatment, in both groups, but without any difference between them. After 6 months, the PD decreased from 5.11±0.56 mm to 2.83±0.47 mm in the test group (

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth \u3e29X and analyze genotypes with four quantitative traits—plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia

Two-stage hepatectomy after autologous CD133+ stem cells administration: a case report

Extreme liver resection can provide a safer option and a chance of cure to otherwise unresectable patients when liver regeneration is boosted by PVE and stem cell administratio

Regenerative Medicine and Diabetes: Targeting the Extracellular Matrix Beyond the Stem Cell Approach and Encapsulation Technology

According to the Juvenile Diabetes Research Foundation (JDRF), almost 1. 25 million people in the United States (US) have type 1 diabetes, which makes them dependent on insulin injections. Nationwide, type 2 diabetes rates have nearly doubled in the past 20 years resulting in more than 29 million American adults with diabetes and another 86 million in a pre-diabetic state. The International Diabetes Ferderation (IDF) has estimated that there will be almost 650 million adult diabetic patients worldwide at the end of the next 20 years (excluding patients over the age of 80). At this time, pancreas transplantation is the only available cure for selected patients, but it is offered only to a small percentage of them due to organ shortage and the risks linked to immunosuppressive regimes. Currently, exogenous insulin therapy is still considered to be the gold standard when managing diabetes, though stem cell biology is recognized as one of the most promising strategies for restoring endocrine pancreatic function. However, many issues remain to be solved, and there are currently no recognized treatments for diabetes based on stem cells. In addition to stem cell resesarch, several β-cell substitutive therapies have been explored in the recent era, including the use of acellular extracellular matrix scaffolding as a template for cellular seeding, thus providing an empty template to be repopulated with β-cells. Although this bioengineering approach still has to overcome important hurdles in regards to clinical application (including the origin of insulin producing cells as well as immune-related limitations), it could theoretically provide an inexhaustible source of bio-engineered pancreases