Unidade de Investigação - CDRsp – Centro para o Desenvolvimento Rápido e Sustentado de Produto
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- Additive manufacturing of tissues and organsPublication . Melchels, Ferry P.W.; Domingos, Marco; Klein, Travis J.; Malda, Jos; Bártolo, Paulo J.; Hutmacher, Dietmar W.Additive manufacturing techniques offer the potential to fabricate organized tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations of cells along multiple axes with high geometric complexity in combination with different biomaterials can be generated. The level of control offered by these computer-controlled technologies to design and fabricate tissues will accelerate our understanding of the governing factors of tissue formation and function. Moreover, it will provide a valuable tool to study the effect of anatomy on graft performance. In this review, we discuss the rationale for engineering tissues and organs by combining computer-aided design with additive manufacturing technologies that encompass the simultaneous deposition of cells and materials. Current strategies are presented, particularly with respect to limitations due to the lack of suitable polymers, and requirements to move the current concepts to practical application.
- Alginate/Aloe Vera Hydrogel Films for Biomedical ApplicationsPublication . Pereira, Rúben F.; Mendes, Ausenda; Bártolo, PauloThis paper describes a methodology to produce hydrogel films, composed of alginate and Aloe vera, for wound healing and drug delivery applications. The films were prepared through the solvent-casting method and subsequently submitted to an additional cross-linking step to improve their properties. Alginate films with different Aloe vera contents (5, 15 and 25%) were prepared and its properties evaluated in terms of thickness, transparency, swelling behavior and in vitro degradation. Results show a positive influence of Aloe vera on the transparency of the films, in both dry and wet state. Films were immersed in acetate buffer at pH 5.5 simulating the value of the skin, to evaluate its water absorption capacity. It was found that water absorption increases as the Aloe vera content increases, suggesting that Aloe vera enhances the hydrophilic properties of the films. The in vitro degradation tests were performed through the incubation of the films, for 10 weeks, in a simulated body fluid at 37°C. After this period, films kept its structure integrity exhibiting a weight loss in the range of 14.1-18.6%.
- BiomanufacturingPublication . Mitsuishi, Mamoru; Cao, Jian; Bártolo, Paulo; Friedrich, Dirk; Shih, Albert J.; Rajurkar, Kamlakar; Sugita, Naohiko; Harada, KanakoBiomedical markets are large and rapidly growing owing to increasing demand for better healthcare services. The development of innovative biomedical systems can produce major breakthroughs in the healthcare industry, and advanced manufacturing technologies can propel such innovations. This paper summarises the field of biomanufacturing: namely, biospecific design constraints, biomechatronics, biofabrication, biodesign, and assembly. This paper presents state-of-the-art research, current problems, and future goals while providing fundamental knowledge required for entry into the biomedical industry. Biomanufacturing provides excellent opportunities for multi-disciplinary collaborations, both in academia and industry, and can lead to further advances in many engineering fields.
- Characterisation of PCL and PCL/PLA Scaffolds for Tissue EngineeringPublication . Patrício, T.; Domingos, M.; A. Gloria; Bártolo, P.This paper investigates the use of PCL and PCL/PLA scaffolds produced using a novel additive biomanufacturing system called BioCell Printing. PCL/PLA blends were prepared using melt blend and solvent casting techniques. Scaffolds with 0/90° architecture and 350 μm of pore size were morphologically evaluated using scanning electron microscopy and atomic force microscopy. Biological tests, using osteosarcoma cell line G-63, were performed using the Alamar Blue Assay and Alkaline Phosphatase Activity. Results show that the BioCell Printing system produces scaffolds with regular and reproducible architecture, presenting no toxicity and enhancing cell attachment and proliferation. It was also possible to observe that the addition of PLA to PCL scaffolds strongly improves the biomechanical performance of the constructs.
- Influence of Hydroxyapatite on Extruded 3D ScaffoldsPublication . Rodriguez, Geraldine; Dias, Juliana; d’Ávila, Marcos Akira; Bártolo, PauloIdeal scaffolds for tissue engineering must mimic the complex characteristics of natural tissues and their mechanical performance. In this work, Polycaprolactone (PCL) and composite Polycaprolactone/Hydroxyapatite (PCL/HA) (75/25) scaffolds were produced by using an extrusion-based process called BioExtruder. The structures were characterized regarding the chemical, thermal, morphological and mechanical properties, in order to investigate the effect of HA addition in the polymeric scaffolds. Results show that the incorporation of HA in the 3D structures improve both the thermal and mechanical properties.
- Levodopa Incorporation in Alginate Membranes for Drug Delivery StudiesPublication . Franco, Margarida Rosa; Viana, Tânia Filipa; Biscaia, Sara; Bártolo, PauloParkinsons Disease (PD) is the second most common progressive neurodegenerative disorder and is referred as a leading cause of neurologic disability. The symptoms and signs of PD result from a decrease of dopamines level in the basal ganglia. Accordingly to this, exogenous substitution with dopamine agonists like levodopa, is used to correct the mechanical disorders at the early stages of the disease. Levodopa is referred as a standard in the treatment of PD. The modern studies of PD drug development and experimental therapeutics focuses on the concept of slowing and targeting the release of levodopa to prolong the therapeutic effect and reduce the number of administrations. The transdermal route was thought to be the best route for providing a progressive supply of levodopa to the systemic circulation. Alginate was chosen as a drug carrier because of its biocompatible and biodegradable properties and also because it has been widely used in drug delivery systems (DDS). The aim of this research work was to produce alginate membranes with and without levodopa. A solvent casting based methodology was used. Calcium chloride was assayed as crosslinking agent. Membranes were characterized using Differential Scanning Calorimetry (DSC) techniques. Drug release was evaluated using UV Spectrophotometry.
- Statistical Modeling of Lower Limb Kinetics During Deep Squat and Forward LungePublication . Roeck, Joris De; Houcke, J. Van; Almeida, D.; Galibarov, P.; Roeck, L. De; Audenaert, Emmanuel A.Purpose: Modern statistics and higher computational power have opened novel possibilities to complex data analysis. While gait has been the utmost described motion in quantitative human motion analysis, descriptions of more challenging movements like the squat or lunge are currently lacking in the literature. The hip and knee joints are exposed to high forces and cause high morbidity and costs. Pre-surgical kinetic data acquisition on a patient-specific anatomy is also scarce in the literature. Studying the normal inter-patient kinetic variability may lead to other comparable studies to initiate more personalized therapies within the orthopedics. Methods: Trials are performed by 50 healthy young males who were not overweight and approximately of the same age and activity level. Spatial marker trajectories and ground reaction force registrations are imported into the Anybody Modeling System based on subject-specific geometry and the state-of-the-art TLEM 2.0 dataset. Hip and knee joint reaction forces were obtained by a simulation with an inverse dynamics approach. With these forces, a statistical model that accounts for inter-subject variability was created. For this, we applied a principal component analysis in order to enable variance decomposition. This way, noise can be rejected and we still contemplate all waveform data, instead of using deduced spatiotemporal parameters like peak flexion or stride length as done in many gait analyses. In addition, this current paper is, to the authors’ knowledge, the first to investigate the generalization of a kinetic model data toward the population. Results: Average knee reaction forces range up to 7.16 times body weight for the forwarded leg during lunge. Conversely, during squat, the load is evenly distributed. For both motions, a reliable and compact statistical model was created. In the lunge model, the first 12 modes accounts for 95.26% of inter-individual population variance. For the maximal-depth squat, this was 95.69% for the first 14 modes. Model accuracies will increase when including more principal components. Conclusion: Our model design was proved to be compact, accurate, and reliable. For models aimed at populations covering descriptive studies, the sample size must be at least 50.
- Virtual Prototyping & Bio Manufacturing in Medical ApplicationsPublication . Bidanda, Bopaya; Bártolo, Paulo Jorge; Bidanda, Bopaya; Bártolo, Paulo JorgeThis new edition focuses on modeling and manufacturing in the field of prototyping and bio manufacturing. The principles utilized draw heavily from more traditional engineering fields including mechanical, industrial, civil (structures), electrical, and bio engineering. Written for engineers and academics seeking a comprehensive overview of virtual prototyping and rapid prototyping, this book discusses in detail applications related to surgery, medical imaging, tissue engineering, bone replacement, and more. Seven new chapters address: • Two-photon polymerization for tissue engineering • Molding in medicine • Organ printing • Skin printing • Nerve regeneration and spinal injury repair • Cartilage regeneration • And Structural analysis of the human shoulder.