In-vivo evaluation of silk fibroin small-diameter vascular grafts: state of art of preclinical studies and animal models

Autologous vein and artery remains the first choice for vascular grafting procedures in small-diameter vessels such as coronary and lower limb districts. Unfortunately, these vessels are often found to be unsuitable in atherosclerotic patients due to the presence of calcifications or to insufficient size. Synthetic grafts composed of materials such as expanded polytetrafluoroethylene (ePTFE) are frequently employed as second choice, because of their widespread availability and success in the reconstruction of larger arteries. However, ePTFE grafts with small diameter are plagued by poor patency rates due to surface thrombogenicity and intimal hyperplasia, caused by the bioinertness of the synthetic material and aggravated by low flow conditions. Several bioresorbable and biodegradable polymers have been developed and tested to exploit such issues for their potential stimulation to endothelialization and cell infiltration. Among these, silk fibroin (SF) has shown promising pre-clinical results as material for small-diameter vascular grafts (SDVGs) because of its favorable mechanical and biological properties. A putative advantage in graft infection in comparison with synthetic materials is plausible, although it remains to be demonstrated. Our literature review will focus on the performance of SF-SDVGs in vivo, as evaluated by studies performing vascular anastomosis and interposition procedures, within small and large animal models and different arterial districts. Efficiency under conditions that more accurately mime the human body will provide encouraging evidence towards future clinical application

Silk Fibroin Vascular Graft: From Design to In Vitro and In Vivo Test

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Stress-Based Lattice Structure Design for a Motorbike Application [version 2; peer review: 2 approved]

Background The “drive by wire” mechanism for managing the throttle is not applied to every modern motorcycle, but it is often managed through a steel wire. Here, there is a cam on the throttle control. Its shape allows the throttle opening to be faster or slower and its angle of rotation, required for full opening, to be greater or less. The maximum angle a rider’s wrist can withstand depends on numerous musculoskeletal mobility factors, often limited by falls or surgery. Methods Using a Progrip knob with interchangeable cams allows the customization of a special cam profile, to ensure the best engine response to throttle rotation and ergonomics for the rider. The use of FEA software and lattice structures, allows to realize a lightweight and efficient design, targeted for fabrication with additive manufacturing technologies. Results The cam was manufactured by exploiting MSLA technology. Finally, a dimensional inspection procedure was performed before assembly. The main result is to have obtained a lighter and cheaper component than the original. Conclusions This study has allowed the design of a mechanical component consisting of innovative shape, light weight, and ergonomics. Furthermore, it demonstrates the effectiveness in the use of lattice structures to enable weight optimization of a component while minimizing the increase in its compliance

Electrospun Silk Fibroin Scaffolds for Tissue Regeneration: Chemical, Structural, and Toxicological Implications of the Formic Acid-Silk Fibroin Interaction

The dissolution of Bombyx mori silk !broin (SF) !lms in formic acid (FA) for the preparation of electrospinning dopes is widely exploited to produce electrospun SF scaffolds. The SilkBridge® nerve conduit is an example of medical device having in its wall structure an electrospun component produced from an FA spinning dope. Though highly volatile, residual FA remains trapped into the bulk of the SF nano!bers. The purpose of this work is to investigate the type and strength of the interaction between FA and SF in electrospun mats, to quantify its amount and to evaluate its possible toxicological impact on human health. The presence of residual FA in SF mats was detected by FTIR and Raman spectroscopy (new carbonyl peak at about 1,725 cm!1) and by solid state NMR, which revealed a new carbonyl signal at about 164.3 ppm, attributed to FA by isotopic 13C substitution. Changes occurred also in the spectral ranges of hydroxylated amino acids (Ser and Thr), demonstrating that FA interacted with SF by forming formyl esters. The total amount of FA was determined by HS-GC/MS analysis and accounted for 247 ± 20 !mol/g. The greatest part was present as formyl ester, a small part (about 3%) as free FA. Approximately 17% of the 1,500 !mol/g of hydroxy amino acids (Ser and Thr) theoretically available were involved in the formation of formyl esters. Treatment with alkali (Na2CO3) succeeded to remove the greatest part of FA, but not all. Alkali-treated electrospun SF mats underwent morphological, physical, and mechanical changes. The average diameter of the !bers increased from about 440 nm to about 480 nm, the mat shrunk, became stiffer (the modulus increased from about 5.5 MPa to about 7 MPa), and lost elasticity (the strain decreased from about 1 mm/mm to about 0.8 mm/mm). Biocompatibility studies with human adult dermal !broblasts did not show signi!cant difference in cell proliferation (313 ± 18 and 309 ± 23 cells/ mm2 for untreated and alkali-treated SF mat, respectively) and metabolic activity. An in-depth evaluation of the possible toxicological impact of residual FA was made using the SilkBridge® nerve conduit as case study, following the provisions of the ISO 10993-1 standard. The Potential Patient Daily Intake, calculated from the total amount of FA determined by HS-GC/MS, was 2.4 mg/day and the Tolerable Exposure level was set to 35.4 mg/day

Three-Layered Silk Fibroin Tubular Scaffold for the Repair and Regeneration of Small Caliber Blood Vessels: From Design to in vivo Pilot Tests

Silk fibroin (SF) is an eligible biomaterial for the development of small caliber vascular grafts for substitution, repair, and regeneration of blood vessels. This study presents the properties of a newly designed multi-layered SF tubular scaffold for vascular grafting (SilkGraf). The wall architecture consists of two electrospun layers (inner and outer) and an intermediate textile layer. The latter was designed to confer high mechanical performance and resistance on the device, while electrospun layers allow enhancing its biomimicry properties and host\u2019s tissues integration. In vitro cell interaction studies performed with adult Human Coronary Artery Endothelial Cells (HCAECs), Human Aortic Smooth Muscle Cells (HASMCs), and Human Aortic Adventitial Fibroblasts (HAAFs) demonstrated that the electrospun layers favor cell adhesion, survival, and growth. Once cultured in vitro on the SF scaffold the three cell types showed an active metabolism (consumption of glucose and glutamine, release of lactate), and proliferation for up to 20 days. HAAF cells grown on SF showed a significantly lower synthesis of type I procollagen than on polystyrene, meaning a lower fibrotic effect of the SF substrate. The cytokine and chemokine expression patterns were investigated to evaluate the cells\u2019 proliferative and pro-inflammatory attitude. Interestingly, no significant amounts of truly pro-inflammatory cytokines were secreted by any of the three cell types which exhibited a clearly proliferative profile. Good hemocompatibility was observed by complement activation, hemolysis, and hematology assays. Finally, the results of an in vivo preliminary pilot trial on minipig and sheep to assess the functional behavior of implanted SF-based vascular graft identified the sheep as the more apt animal model for next medium-to-long term preclinical trials

3D printed custom gas cam for race bike application using Progrip® lock on grips mod.708

Background: The “drive by wire” mechanism for managing the throttle is not applied to every modern motorcycle, but it is often managed through a steel wire. Here, there is a cam on the throttle control. Its shape allows the throttle opening to be faster or slower and its angle of rotation, required for full opening, to be greater or less. The maximum angle a rider's wrist can withstand depends on numerous musculoskeletal mobility factors, often limited by falls or surgery. Methods: Using a Progrip knob with interchangeable cams allows the customization of a special cam profile, to ensure the best engine response to throttle rotation and ergonomics for the rider. The use of FEA software and lattice structures, allows to realize a lightweight and efficient design, targeted for fabrication with additive manufacturing technologies. Results: The cam was manufactured by exploiting MSLA technology. Finally, a dimensional inspection procedure was performed before assembly. The main result is to have obtained a lighter and cheaper component than the original. Conclusions: This study has allowed the design of a mechanical component consisting of innovative shape, light weight, and ergonomics. Furthermore, it demonstrates the effectiveness in the use of lattice structures to enable weight optimization of a component while minimizing the increase in its compliance

Reverse Engineering of a Racing Motorbike Connecting Rod

The following scientific paper aims to analyze in detail the methodology for reverse engineering of a racing motorcycle connecting rod. The objective is to start with a product available on the market as a spare part, reconstruct its CAD model with a high standard of accuracy, then proceed with lightening modifications to arrive at a new, improved design. The innovative aspect of the procedure lies in the fact that in order to ensure accuracy on the order of a tenth of a millimeter during reconstruction, it was decided to use a FARO articulated arm laser to scan the component’s outer surface. By taking advantage of appropriate redesign CAD software (Geomagic Design X), a reconstruction can proceed within the high standard of accuracy imposed. In conclusion, the modifications made through material removal allow an improvement in product efficiency, ensuring high performance