A Cutting Force and Hole Geometry Study for Precision Deep-Hole Microdrilling of Magnesium.

Size effects, high thrust forces, limited heat dissipation, and tool deterioration are just some of the challenges that deep microdrilling poses, underscoring the importance of effective process control to ensure quality. In this paper, an investigation performed on a microdrilling process on pure magnesium using a 0.138 mm diameter microdrill to achieve an aspect ratio equal to 36 is proposed. The effect of the variation of the cutting parameters feed per tooth fz and cutting speed vc was studied on thrust force, supporting hole quality evaluation in terms of burr height, entrance, and inner diameters. The results showed that fz significantly influences the hole quality. In fact, as fz increases, the burr height decreases and the inner diameter approaches the nominal diameter. However, optimizing the hole geometry with high feed per tooth values increases the thrust forces, compromising tool life. In fact, a significant dependence of the thrust force on both cutting parameters was found. In this scenario, increasing vc can mitigate the high thrust forces by inducing material softening. The study results improve precision manufacturing by refining parameters, ensuring the quality and reliability of magnesium-based microcomponents.

A Deep-Hole Microdrilling Study of Pure Magnesium for Biomedical Applications.

The mechanisms of deep-hole microdrilling of pure Mg material were experimentally studied in order to find a suitable setup for a novel intraocular drug delivery device prototyping. Microdrilling tests were performed with 0.20 mm and 0.35 mm microdrills, using a full factorial design in which cutting speed vc and feed fz were varied over two levels. In a preliminary phase, the chip shape was evaluated for low feeds per tooth down to 1 µm, to verify that the chosen parameters were appropriate for machining. Subsequently, microdrilling experiments were carried out, in which diameter, burr height and surface roughness of the drilled holes were examined. The results showed that the burr height is not uniform along the circumference of the holes. In particular, the maximum burr height increases with higher cutting speed, due to the thermal effect that plasticizes Mg. Hole entrance diameters are larger than the nominal tool diameters due to tool runout, and their values are higher for high vc and fz. In addition, the roughness of the inner surface of the holes increases as fz increases.

Meniscus Matrix Structural and Biomechanical Evaluation: Age-Dependent Properties in a Swine Model.

The analysis of the morphological, structural, biochemical, and mechanical changes of the Extracellular Matrix (ECM), which occur during meniscus development, represents the goal of the present study. Medial fully developed menisci (FD, 9-month-old pigs), partially developed menisci (PD, 1-month-old piglets), and not developed menisci (ND, from stillbirths) were collected. Cellularity and glycosaminoglycans (GAGs) deposition were evaluated by ELISA, while Collagen 1 and aggrecan were investigated by immunohistochemistry and Western blot analyses in order to be compared to the biomechanical properties of traction and compression tensile forces, respectively. Cellularity decreased from ND to FD and GAGs showed the opposite trend (p < 0.01 both). Collagen 1 decreased from ND to FD, as well as the ability to resist to tensile traction forces (p < 0.01), while aggrecan showed the opposite trend, in accordance with the biomechanics: compression test showed that FD meniscus greatly resists to deformation (p < 0.01). This study demonstrated that in swine meniscus, clear morphological and biomechanical changes follow the meniscal maturation and specialization during growth, starting with an immature pattern (ND) to the mature organized meniscus of the FD, and they could be useful to understand the behavior of this structure in the light of its tissue bioengineering.

Evolution of Meniscal Biomechanical Properties with Growth: An Experimental and Numerical Study.

The menisci of the knee are complex fibro-cartilaginous tissues that play important roles in load bearing, shock absorption, joint lubrication, and stabilization. The objective of this study was to evaluate the interaction between the different meniscal tissue components (i.e., the solid matrix constituents and the fluid phase) and the mechanical response according to the developmental stage of the tissue. Menisci derived from partially and fully developed pigs were analyzed. We carried out biochemical analyses to quantify glycosaminoglycan (GAG) and DNA content according to the developmental stage. These values were related to tissue mechanical properties that were measured in vitro by performing compression and tension tests on meniscal specimens. Both compression and tension protocols consisted of multi-ramp stress-relaxation tests comprised of increasing strains followed by stress-relaxation to equilibrium. To better understand the mechanical response to different directions of mechanical stimulus and to relate it to the tissue structural composition and development, we performed numerical simulations that implemented different constitutive models (poro-elasticity, viscoelasticity, transversal isotropy, or combinations of the above) using the commercial software COMSOL Multiphysics. The numerical models also allowed us to determine several mechanical parameters that cannot be directly measured by experimental tests. The results of our investigation showed that the meniscus is a non-linear, anisotropic, non-homogeneous material: mechanical parameters increase with strain, depend on the direction of load, and vary among regions (anterior, central, and posterior). Preliminary numerical results showed the predominant role of the different tissue components depending on the mechanical stimulus. The outcomes of biochemical analyses related to mechanical properties confirmed the findings of the numerical models, suggesting a specific response of meniscal cells to the regional mechanical stimuli in the knee joint. During maturation, the increase in compressive moduli could be explained by cell differentiation from fibroblasts to metabolically active chondrocytes, as indicated by the found increase in GAG/DNA ratio. The changes of tensile mechanical response during development could be related to collagen II accumulation during growth. This study provides new information on the changes of tissue structural components during maturation and the relationship between tissue composition and mechanical response.

Evaluation of the ocular fluid dynamic effects on intraocular magnesium-based device: A comparison between CFD and FSI approaches.

Magnesium is an essential element for the ocular functions and used for the realization of medical devices due to its low corrosion resistance, bioresorbable nature and biocompatibility. Wet age-related macular degeneration is one of the main causes of blindness with patients treated by intravitreal injections of inhibitor drugs. According to the need to reduce the number of injections, the development of new drug delivery devices able to extend the therapeutical outcomes is mandatory and magnesium can be considered as a promising candidate. The aim of the work concerns the evaluation of the ocular fluid dynamic role on a magnesium-based device placed in the vitreous chamber. Particularly, the fluid-induced shear stress field on the surfaces in contact with the liquefied vitreous was studied. Both computational fluid dynamic and fluid-structure interaction approaches were proposed and then compared. Saccadic motion was implemented to recreate the vitreous fluid dynamics. High changes in terms of fluid-induced shear stress field varying the CFD and FSI numerical approaches and kinematic parameters of the saccadic function can be noticed. The comparison between CFD and FSI approaches showed minor significant differences and both implementations suggested the possibility to obtain a uniform and controlled corrosion of the device.

A drug delivery analysis of large molecules in ocular vitreous chamber: Dependency on saccadic movements after intravitreal injection.

The purpose of this study is to investigate the effect of vitreous sloshing induced by saccades on the intravitreal delivery of large molecule drugs. The vitreous body was considered in its age-related liquefaction condition. Fluid dynamics and large molecule distribution were described by the coupling of mass conservation's and Fick's laws with continuity and momentum equations for a Newtonian incompressible fluid in a 3D unsteady analysis. Two injection sites were analyzed, in both the mixing effect of a 50° periodic saccade leads to uniform drug distribution in 30 s of simulation, the initial bolus site being left after 3 s of simulation. In absence of saccadic movements, the dominant transport contribution is the diffusive one and large molecules hardly reach their uniform distribution inside the vitreous cavity. A model describing the intravitreal distribution of large molecules in presence of saccades was developed, improving the understanding of drug transport mechanism after an intravitreal injection and highlighting how advection contribution enhances its distribution in the vitreous chamber.

Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model.

Tendon tissue ruptures often require the replacement of damaged tissues. The use of auto- or allografts is notoriously limited due to the scarce supply and the high risks of immune adverse reactions. To overcome these limitations, tissue engineering (TE) has been considered a promising approach. Among several biomaterials, decellularized xenografts are available in large quantity and could represent a possible solution for tendon reconstruction. The present study is aimed at evaluating TE xenografts in Achilles tendon defects. Specifically, the ability to enhance the biomechanical functionality, while improving the graft interaction with the host, was tested. The combination of decellularized equine-derived tendon xenografts with or without the matrix repopulation with autologous bone marrow mesenchymal stem cells (BMSCs) under stretch-perfusion dynamic conditions might improve the side-to-side tendon reconstruction. Thirty-six New Zealand rabbits were used to create 2 cm long segmental defects of the Achilles tendon. Then, animals were implanted with autograft (AG) as the gold standard control, decellularized graft (DG), or in vitro tissue-engineered graft (TEG) and evaluated postoperatively at 12 weeks. After sacrifice, histological, immunohistochemical, biochemical, and biomechanical analyses were performed along with the matrix metalloproteinases. The results demonstrated the beneficial role of undifferentiated BMSCs loaded within decellularized xenografts undergoing a stretch-perfusion culture as an immunomodulatory weapon reducing the inflammatory process. Interestingly, AG and TEG groups exhibited similar results, behaved similarly, and showed a significant superior tissue healing compared to DG in terms of newly formed collagen fibres and biomechanical parameters. Whereas, DG demonstrated a massive inflammatory and giant cell response associated with graft destruction and necrosis, absence of type I and III collagen, and a higher amount of proteoglycans and MMP-2, thus unfavourably affecting the biomechanical response. In conclusion, this in vivo study suggests a potential use of the proposed tissue-engineered constructs for tendon reconstruction.

A Combined Approach for the Analysis of Ocular Fluid Dynamics in the Presence of Saccadic Movements.

One of the main ocular diseases is age-related macular degeneration, actually treated with antibodies injections into the eye. This problem has been faced by computational approaches, taking into account either the influence of the tissues surrounding the vitreous, or the saccades. The aim of this work is to propose a combined fluid dynamic model of the vitreous chamber that analyses the impact of the saccades on the fluid dynamic mechanisms. The ocular vitreous humor was modeled considering liquefaction occurring in presence of age-related macular degeneration. We identified two kinds of boundary conditions, one related to the physiological environment outside the chamber, and one related to the saccades. The scleral hydraulic conductivity was evaluated by means of experimental permeability tests. An exponential decay was used to describe the trend of the scleral hydraulic conductivity with the acting pressure drop. The streamline analysis shows two main stagnant regions on the equatorial plane and peculiar fluid dynamics in absence of saccades. This study demonstrates the major role played by the saccades in determining the fluid dynamic mechanisms inside the vitreous chamber of the eye and represents a powerful tool to investigate vitreous dynamics and its relation to clinical issues.

Terminal sterilization of equine-derived decellularized tendons for clinical use.

In the last few years, the demand for tissue substitutes has increased and decellularized matrices has been widely proposed in the medical field to restore severe damages thanks to high biocompatibility and biomechanical properties similar to the native tissues. However, biological grafts represent a potential source of contamination and disease transmission; thus, there is the need to achieve acceptable levels of sterility. Several sterilization methods have been investigated with no consensus on the outcomes in terms of minimizing structural damages and preserving functional features of the decellularized matrix for transplantation in humans. With the aim of making decellularized tendons safe for clinical use, we evaluated the cytocompatibility, and biochemical, structural and biomechanical variations of decellularized equine tendons sterilized with peracetic acid or ß-irradiation and differently wet- or dry- stored at 4°C or -80°C, respectively. Considering that both sterilization and long-term storage are crucial steps that could not be avoided, our results pointed at ionizing ß-rays as terminal sterilization method for decellularized grafts followed by frozen dry storage. Indeed, this approach can maintain the integrity of collagen-based structures and can avoid biomechanical changes, thus making xenogeneic decellularized tendons a promising candidate for clinical use.

Modeling the fluid-dynamics and oxygen consumption in a porous scaffold stimulated by cyclic squeeze pressure.

The architecture and dynamic physical environment of tissues can be recreated in-vitro by combining 3D porous scaffolds and bioreactors able to apply controlled mechanical stimuli on cells. In such systems, the entity of the stimuli and the distribution of nutrients within the engineered construct depend on the micro-structure of the scaffolds. In this work, we present a new approach for optimizing computational fluid-dynamics (CFD) models for the investigation of fluid-induced forces generated by cyclic squeeze pressure within a porous construct, coupled with oxygen consumption of cardiomyocytes. A 2D axial symmetric macro-scaled model of a squeeze pressure bioreactor chamber was used as starting point for generating time dependent pressure profiles. Subsequently the fluid movement generated by the pressure fields was coupled with a complete 3D micro-scaled model of a porous protein cryogel. Oxygen transport and consumption inside the scaffold was evaluated considering a homogeneous distribution of cardiomyocytes throughout the structure, as confirmed by preliminary cell culture experiments. The results show that a 3D description of the system, coupling a porous geometry and time dependent pressure driven flow with fluid-structure-interaction provides an accurate and meaningful description of the microenvironment in terms of shear stress and oxygen distribution than simple stationary 2D models.

Agricultural biotechnology and smallholder farmers in developing countries.

Agricultural biotechnology holds much potential to contribute towards crop productivity gains and crop improvement for smallholder farmers in developing countries. Over 14 million smallholder farmers are already benefiting from biotech crops such as cotton and maize in China, India and other Asian, African and Central/South American countries. Molecular breeding can accelerate crop improvement timescales and enable greater use of diversity of gene sources. Little impact has been realized to date with fruits and vegetables because of development timescales for molecular breeding and development and regulatory costs and political considerations facing biotech crops in many countries. Constraints to the development and adoption of technology-based solutions to reduce yield gaps need to be overcome. Full integration with broader commercial considerations such as farmer access to seed distribution systems that facilitate dissemination of improved varieties and functioning markets for produce are critical for the benefits of agricultural biotechnology to be fully realized by smallholders. Public-private partnerships offer opportunities to catalyze new approaches and investment while accelerating integrated research and development and commercial supply chain-based solutions.