Artificial Immune Algorithm Based Gravimetric Fluid Dispensing Machine

One of the most prominent methods used in handling the end process for materials-mixing is by having a dispensing system. An effective dispensing method using Pulse Width Modulation (PWM) at the end of the dispensing sequence with Artificial Immune System (AIS) automatic dispensing parameter fine tuning capability is proposed by optimizing the components of Dispensing Time and Stopping Time Delay to obtain constant and accurate reading from the precision balance scale. Based on the new dispensing sequence, experimental tests had been carried out using different materials with varying viscosities. The results denote that the combination of both PWM and AIS techniques would minimize the error rate for overshooting while exhibiting better accuracy. These are important in order to overcome the limitations of the conventional volumetric dispensing and manual parameter tuning presently applied in the dispensing system used in the coatings industry

MODELLING AND IN VIVO MONITORING OF THE TIME DEPENDENT MECHANICAL PROPERTIES OF TISSUE ENGINEERING SCAFFOLDS

When organs and tissue fail either due to pre-existing disease progression or by accidental damage, current state of the art treatment involves the replacement of the damaged or diseased tissue with new donor derived organs/tissue. The limitations of these current approaches include a limited supply of tissue for treatments and the immune response of the patient’s own body against the new implanted tissue/organs. To solve these issues, tissue engineering aims to develop artificial analogs derived from a patient’s own cells instead of donor tissue/organs for treatment. To this end, a promising approach, known as scaffold-based tissue engineering, is to seed engineered constructs or scaffolds with cells to form artificial analogs, which then develop with time into new tissue/organs for implantation. The mechanical properties of the scaffold play a critical role in the success of scaffold-based treatments, as the scaffold is expected to provide a temporary support for the generation of new tissue/organs without causing failure at any time during the treatment process. It is noted that due to the degradation of scaffold in the treatment process, the mechanical properties of the scaffold are not constant but change with time dynamically. This raises two scientific issues; one is the representation of the time-dependent mechanical properties and the other one is the monitoring of these properties, especially in the in vivo environments (i.e., upon the implantation of scaffolds into animal/patient bodies). To address these issues, this research is aimed at performing a novel study on the modelling and in vivo monitoring of the time dependent mechanical properties of tissue engineering scaffolds. To represent the time-dependent mechanical properties of a scaffold, a novel model based on the concept of finite element model updating is developed. The model development involves three steps: (1) development of a finite element model for the effective mechanical properties of the scaffold, (2) parametrizing the finite element model by selecting parameters associated with the scaffold microstructure and/or material properties, which vary with scaffold degradation, and (3) identifying selected parameters as functions of time based on measurements from the tests on the scaffold mechanical properties as they degrade. To validate the developed model, scaffolds were made from the biocompatible polymer polycaprolactone (PCL) mixed with hydroxyapatite (HA) nanoparticles and their mechanical properties were examined in terms of the Young modulus. Based on the bulk degradation exhibited by the PCL/HA scaffold, the molecular weight was selected for model updating. With the identified molecular weight, the finite element model v developed was effective for predicting the time-dependent mechanical properties of PCL/HA scaffolds during degradation . To monitor and characterize scaffold mechanical properties in vivo, novel methods based on synchrotron-based phase contrast imaging and finite element modeling were developed. The first method is to represent the scaffold mechanical properties from the measured deflection. In this method, the phase contrast imaging is used to characterize the scaffold deflection caused by ultrasound radiation forces; and the finite element modelling is used to represent the ultrasonic loading on the scaffold, thus predicting the mechanical properties from the measured deflection. The second method is to characterize the scaffold degradation due to surface erosion, which involves the remote sensing of the time dependent morphology of tissue scaffolds by phase contrast imaging and the estimation of time dependent mass loss of the scaffolds from the sensed morphology. The last method is to relate the elastic mechanical property and nonlinear stress-strain behavior to the scaffold geometry, both changing with time during surface erosion. To validate the above methods, scaffolds was made from varying biomaterials (PLGA and PCL) and their mechanical properties (degradation, mass loss, and elastic modulus) were examined experimentally. The results obtained illustrate the methods developed in this research are effective to monitor and characterize scaffold mechanical properties. The significance of this research is that the model developed for the scaffold mechanical properties can be used in the design of scaffolds with the desired mechanical properties, instead of the trial and error methods typical in current scaffold design; and that these novel monitoring methods based on synchrotron imaging can be used to characterize the scaffold time-dependent mechanical properties in the in vivo environments, representing an important advance in tissue engineering

Additive Manufacturing Methodology and System for Fabrication of Porous Structures with Functionally Graded Properties

The focus of this dissertation is on the development of an additive manufacturing system and methodology for fabricating structures with functionally graded porous internal properties and complex three-dimensional external characteristics. For this purpose, a multi-scale three-dimensional printing system was developed, with capabilities and fabrication methodologies refined in the context of, but not limited to, manufacturing of porous bone substitutes. Porous bone implants are functionally graded structures, where internally, the design requires a gradient in porosity and mechanical properties matching the functional transition between cortical and cancellous bone regions. Geometrically, the three-dimensional shape of the design must adhere to the anatomical shape of the bone tissue being replaced. In this work, control over functionally graded porous properties was achieved by integrating specialized modules in a custom-made additive manufacturing system and studying their effect on fabricated constructs. Heterogeneous porous properties were controlled by: (i) using a micro-syringe deposition module capable of embedding sacrificial elements with a controlled feature size within the structure, (ii) controlling the amount of binder dispersed onto the powder substrate using a piezoelectric printhead, (iii) controlling the powder type or size in real-time, and/or (iv) selecting the print layer stacking orientation within the part. Characterization methods included differential scanning calorimetry (DSC)-thermo gravimetric analysis (TGA) to establish the thermal decomposition of sacrificial elements, X-ray diffraction (XRD) and dispersive X-ray spectroscopy (EDAX) to investigate the chemical composition and crystallinity, scanning electron microscopy (SEM) and optical microscopy to investigate the physical and structural properties, uniaxial mechanical loading to establish compressive strength characteristics, and porosity measurements to determine the bulk properties of the material. These studies showed that the developed system was successful in manufacturing embedded interconnected features in the range of 100-500 $\mu m$, with a significant impact on structural properties resulting in bulk porosities in the range of 30-55% and compressive strength between 2-50 MPa. In this work, control over the the three-dimensional shape of the construct was established iteratively, by using a silhouette extraction image processing technique to determine the appropriate anisotropic compensation factors necessary to offset the effects of shrinkage in complex-shaped parts during thermal annealing. Overall shape deviations in the range of +/- 5-7 % were achieved in the second iteration for a femoral condyle implant in a sheep model. The newly developed multi-scale 3DP system and associated fabrication methodology was concluded to have great potential in manufacturing structures with functionally graded properties and complex shape characteristics

Medication safety in intravenous drug administration : error causes and systemic defenses in hospital setting

Intravenous administration of drugs is associated with the highest medication error frequencies and more serious consequences to the patient than any other administration route. The bioavailability of intravenously administered medication is high, the therapeutic dose range is often narrow, and effects are hard to undo. Many intravenously administered drugs are high-alert medications, bearing a heightened risk of causing significant patient harm if used in error. Smart infusion pumps with dose error-reduction software can be used to prevent harmful medication errors in high-risk clinical settings, such as neonatal intensive care units. This study investigated intravenous medication safety in hospital settings by identifying recent research evidence related to systemic causes of medication errors (Study I) and systemic defenses to prevent these errors (Study II). The study also explored the development of dose-error reduction software in a neonatal intensive care unit (Study III). A systems approach to medication risk management based on the Theory of Human Error was applied as a theoretical framework. The study was conducted in two phases. In the first phase, a systematic review of recent research evidence on systemic causes of intravenous medication errors (Study I) and systemic defenses aiming to prevent these errors (Study II) was carried out. In Study I, 11 studies from six countries were included in the analysis. Systemic causes related to prescribing (n=6 studies), preparation (n=6), administration (n=6), dispensing and storage (n=5) and treatment monitoring (n=2) were identified. Insufficient actions to secure safe use of high-alert medications, lack of knowledge of the drug, failures in calculation tasks and in double-checking procedures, and confusion between look-alike, sound-alike medications were the leading causes of intravenous medication errors. The number of the included studies was limited, all of them being observational studies and graded as low quality. In Study II, 46 studies from 11 countries were included in the analysis. Systemic defenses related to administration (n=24 studies), prescribing (n=8), preparation (n=6), treatment monitoring (n=2), and dispensing (n=1) were identified. In addition, five studies explored defenses related to multiple stages of the medication use process. Defenses including features of closed-loop medication management systems appeared in 61% of the studies, smart pumps being the defense most widely studied (24%). The evidence quality of the included articles was limited, as 83% were graded as low quality, 13% moderate quality, and only 4% high quality. A mixed-methods study was conducted in the second phase, applying qualitative and quantitative methods (Study III). Medication error reports were used to develop simulation-type test cases to assess the suitability of dosing limits in a neonatal intensive care unit’s smart infusion pump drug library. Of all medication errors reported in the neonatal intensive care unit, 3.5% (n=21/601) involved an error or near-miss related to wrong infusion rate. Based on the identified error mechanisms, 2-, 5-, and 10-fold infusion rates and mix-ups between infusion rates of different drugs were established as test cases. When conducting the pump programming for the test cases (n=226), no alerts were triggered with infusion rates responding to the usual dosages (n=32). Of the erroneous 2-, 5-, and 10-fold infusion rates, 73% (n = 70/96) caused an alert. Mix-ups between infusion rates triggered an alert only in 24% (n=24/98) of the test cases. This study provided an overview of recent research evidence related to intravenous medication safety in hospital settings. Current intravenous medication systems remain vulnerable, which can result in patient harm. While in-hospital intravenous medication use processes are developing towards closed-loop medication management systems, combinations of different defenses and their effectiveness in error prevention should be explored. In addition to improved medication safety, implementing new systemic defenses leads to new error types, emphasizing the importance of continuous proactive risk management as an essential part of clinical practice.Laskimonsisäiseen lääkkeen annosteluun liittyy merkittävä lääkityspoikkeamien ja vakavien haittatapahtumien riski. Sairaaloissa käytetään useita laskimoon annosteltavia suuren riskin lääkkeitä, joiden virheellinen käyttö johtaa muita lääkkeitä todennäköisemmin vakaviin haittoihin. Tässä tutkimuksessa tunnistettiin järjestelmällisen kirjallisuuskatsauksen perusteella lääkityspoikkeamien järjestelmälähtöisiä syitä (osatyö I) sekä lääkehoitoprosessin suojauksia (osatyö II). Lisäksi tutkittiin älyinfuusiopumppujen käyttöönottoa vastasyntyneiden teho-osastolla. Teoreettisena viitekehyksenä käytettiin inhimillisen erehdyksen teoriaa ja järjestelmänäkökulmaa lääkehoitoprosessin riskien hallinnassa. Osatyön I aineistosta (n=11 tutkimusta) tunnistettiin lääkityspoikkeamien syntyyn vaikuttavia järjestelmälähtöisiä syitä, jotka liittyivät lääkehoidon määräämiseen (n=6), käyttökuntoon saattoon (n=6), antoon (n=6), jakeluun ja varastointiin (n=5) sekä seurantaan (n=2). Yleisimpiä syitä olivat riittämättömät toimenpiteet suuren riskin lääkkeiden turvallisen käytön varmistamisessa, ammattilaisten heikot tiedot lääkkeistä, virheet laskutoimituksissa ja kaksoistarkistuksissa sekä toisiltaan näyttävien ja kuulostavien lääkkeiden sekaantuminen keskenään. Osatyön II aineistossa (n=46 tutkimusta) kuvattiin lääkehoitoprosessin suojauksia, jotka liittyivät lääkkeiden annosteluun (n=24), määräämiseen (n=8), käyttökuntoon saattoon (n=6), hoidon seurantaan (n=2) ja jakeluun (n=1). Lisäksi viidessä tutkimuksessa kuvattiin useaan lääkehoitoprosessin vaiheeseen liittyviä suojauksia. Katkeamattoman lääkehoitoprosessin piirteitä tunnistettiin 61 prosentissa tutkimuksista ja älyinfuusiopumput olivat eniten tutkittu suojaus (24 %). Osatyö III toteutettiin monimenetelmätutkimuksena. Vastasyntyneiden teho-osastolla raportoitujen lääkityspoikkeamien pohjalta kehitettiin simulaatiotyyppisiä testitapauksia, joilla arvioitiin annosrajojen sopivuutta älyinfuusiopumppujen lääkekirjastoon. Lääkityspoikkeamista 3,5 % (n=21/601) liittyi väärään infuusionopeuteen ja niiden perusteella testitapauksiksi määritettiin 2-, 5- ja 10-kertaiset infuusionopeudet sekä eri lääkkeiden antonopeuksien sekaantuminen keskenään. Testitapauksissa (n=226) infuusiopumput eivät hälyttäneet tavanomaisia nopeuksia ohjelmoitaessa (n=32), mutta virheellisistä infuusionopeuksista 73 % (n=70/96) aiheutti hälytyksen. Nopeuksien sekaantuminen keskenään laukaisi hälytyksen vain 24 %:ssa (n=24/98) testitapauksista. Sairaaloiden laskimonsisäinen lääkehoitoprosessi kehittyy kohti katkeamatonta lääkehoitoprosessia, mutta se on edelleen altis lääkityspoikkeamille. Kirjallisuuskatsauksiin sisällytettyjen tutkimusten laatu oli pääosin heikko, joten lääkityspoikkeamien riskitekijöitä ja suojauksia tulee edelleen tutkia yhä laadukkaammissa tutkimusasetelmissa. Uusien suojausten käyttöönotto muuttaa myös riskikohtia, mikä korostaa ennakoivan riskienhallinnan merkitystä osana sairaaloiden toimintaa

Abstract Book

Proceedings of APP 11th ANNUAL CONVENTION AND 5th INDO SWISS CONFERENCE 16 – 17, DEC-2022 &nbsp

Poster presentations of Congressus Pharmaceuticus Hungaricus XVI.

Abstracts of poster presentations of Congressus Pharmaceuticus Hungaricus XVI

An examination of the response of East Asian lacquer films to changes in environmental conditions

This work addresses the material properties and behaviour of Japanese lacquers (urushi) coatings similar to those found on the Mazarin Chest, an important Japanese lacquerware artefact currently displayed in the Toshiba Gallery of Japanese Art at the Victoria and Albert Museum (V&A) in London. For almost four centuries, the Mazarin Chest has been displayed in uncontrolled environmental conditions and has been exposed to a range of lighting conditions. As a result, the Mazarin Chest has deteriorated and started to suffer from different kinds of damage. However, the optimal conservation approach to repairing this damage is not known and as a consequence, research on urushi and related materials is of great interest. For the first time, the effect of changing relative humidity (RH) on the response of urushi is investigated by examining the deflection of a glass substrate coated with a thin film of urushi. Phase shifting interferometry was employed to measure this deflection, from which the in-plane stress developed in the system due to the expansion mismatch in the bilayer was calculated. This was performed for aged (exposed to ultra-violet radiation) and non- aged urushi films. The film stress was observed over 66 hrs under 30%, 36% and 42% RH, while the stress response was observed over 7 hrs during exposure to 60%, 54% and 48% RH. During exposure to 30%, 36% and 42% RH and for both non-aged and aged urushi films, tensile in-plane stress was observed. It was seen to reach a peak value then relax over a longer time scale. The stresses develop in the non-aged urushi films were found to be higher than the stresses developed in the aged urushi films. The peak stress values for non-aged and aged urushi films were found to increase when increasing the difference between the storage RH (75%) and the target RH. When the non-aged and aged urushi films were subjected to a step change from low RH (30%, 36% and 42%) to high RH (60%, 54% and 48% RH), a compression inplane stress was observed and in this case, the aged urushi films exhibited higher stresses than those developed in non-aged urushi films. II To predict the behaviour of the urushi films, a simple 1D model of stress has been proposed. It shows reasonable agreement against the experimental stress measurements when the RH changes from 75% to 30%, 36% and 42% respectively, for both nonaged and aged urushi films. Furthermore, the model is extended to predict the stress response as a function of depth for non-aged urushi layers above an aged layer. For both the upper urushi layer (non-aged) and the lower urushi layer (aged), the model suggests that decreasing the layer depth results in an increase in the stress levels. In addition to the stress response measurements and in order to fully characterise the mechanics of urushi, mechanical properties were determined for non-aged and aged urushi films under different RH levels. These including the moisture diffusion coefficients, the elastic modulus, the tensile strength at break, the elongation at break, and the viscoelastic properties. The moisture diffusion coefficients were determined from the sorption and desorption curves when urushi films, non-aged and aged, subjected to step changes in RH. The results showed that the moisture diffusion coefficients were independent of the moisture content for non-aged and aged urushi. A strong dependence of the elastic modulus and the elongation at failure on the RH has been observed for non-aged and aged urushi films. At all strain rates used and as the RH increases, a significant reduction in tensile elastic modulus and an increase in the elongation at failure were observed. As a result of the UV ageing, no plastic deformation was observed in the stress-strain curves at any RH or tensile speeds. Creep recovery behaviours of non-aged and aged urushi under 30%, 50% and 75% RH and different stress levels were studied. The overall deformation levels at 75% RH for non-aged films were found to be higher than that at 30% RH and the aged films exhibited less stiffness. This trend reflects the strong influence of water, as a plasticizer, on urushi films. The variation of the elastic recovery with the applied stress and the RH for non-aged and aged urushi films were determined from the recovery behaviour. The results showed that the amount of elastic recovery at 30% RH for non-aged urushi was higher III than that for aged urushi films at all stress values. At 50% RH and 75% RH, the aged urushi films recovered to a greater degree than non-aged urushi films. The 4-element Burger‟s model was used for quantitative characterisation of the creep recovery curves to determine the viscoelastic properties for urushi films and their dependence on the RH and UV ageing. It was found that the RH has a strong effect on the viscoelastic properties for both non-aged and aged urushi films. A significant decrease in these parameters has been observed when the RH has been increased suggesting that the films tend to become soft as a result of the high mobility of the molecular chains under elevated RH. We have proposed a methodology to identify the effectiveness of the Japanese traditional consolidation processes that are used to consolidate the formation of microcracks on lacquerware surfaces. A rectangular aluminium substrate, covered with a thin film of aged urushi, was mechanically loaded using three point bending device and the in-plane urushi surface displacement profile was obtained through phase shifting digital speckle pattern interferometry (DSPI). A comparison of the displacement profiles before and after creating a ‟v‟ notch along the film showed an anomalous profile around the notch. While after consolidate the notch, no anomaly in the displacement profiles were observed. The potential for DSPI to play a key role in investigating consolidation mechanics has been demonstrated with the detection of the surface displacement around a notch before and after consolidation

Biomimetic bone grafts: from the lab to the clinic

Aplicat embargament des de la data de defensa fins el dia 17/6/2022Bone grafting is a common medical practice in today’s society, being bone the second most transplanted tissue worldwide after blood. Therefore, it represents a field of major interest for both, biomedical research and the biomedical industry. Despite the ability of bone to self-heal, in some scenarios where defects are large or complex, bone grafts are essential for a successfully regeneration. Although autografting is still today the gold standard in terms of biological performance, the limited availability and morbidity associated with this practice drive to search for alternatives. Synthetic grafts arise as a promising option due to their unlimited availability and the possibility to tune their structure and composition for optimal performance. The present thesis explores biomimetic calcium deficient hydroxyapatite (CDHA), a promising material for synthetic bone grafts, in a translational-oriented perspective. Two product presentations are studied: A more conventional granulated conformation and a 3D printed personalised format. Chapter 1 offers a brief overview of bone biology, as well as a state of the art of the currently available bone grafting strategies found in the literature. Chapter 2 focuses on the validation of the in vivo performance of CDHA granules compared to the well- established bovine xenograft particulate grafts in a dental indication in miniature swine. It is concluded that both biomaterials meet the requirements for bone grafting, (i.e., biocompatibility, osseointegration, and osteoconduction). Moreover, it is revealed that granule morphology is a key factor to ensure the preservation of the grafted volume. In the following chapters, the focus is moved to the 3D printed personalised CDHA bone grafts. Chapter 3 investigates different approaches to accelerate the consolidation process of the 3D printed grafts in order to make the technology more suitable for industrial applications, and develops a hydrothermal treatment that reduces the reaction time to 30 minutes instead of the 7 days needed in the biomimetic approach. Despite the slight differences in physicochemical properties associated to this approach (e.g., microstructure, crystalline phase, microporosity, specific surface area), the resulting scaffolds support adhesion and proliferation of rat mesenchymal stem cells, suggesting its potential as bone graft substitutes. In Chapter 4 the hydrothermal route introduced in the previous chapter is compared to the long-established biomimetic treatment in terms of the in vivo performance of the 3D-printed scaffolds through orthotopic implantation in rabbit condyle monocortical defects. The samples treated with this new process, in addition to the excellent biocompatibility, osseointegrative and osteoconductive properties characteristic of biomimetic CDHA, exhibit a significantly higher amount of newly formed bone than the biomimetic counterpart. This enhanced performance is attributed to the higher permeability of the microstructure, as demonstrated with a protein adsorption test. Chapter 5 explores a strategy to enhance the degree of concavity and specific surface area of 3D printed structures obtained by microextrusion, by using nozzles with non-circular cross-sections. Besides achieving the intended purpose and characterising the 3D-printed structures, different technical constraints for the printing process associated to the use of non-circular nozzles are identified. In a further step, this developed technology is applied to the fabrication of 3D-printed bone grafts with concave filament surfaces and tested in vivo in a rabbit condyle orthotopic model in Chapter 6. It is found that using strands with star-shaped cross-sections helps to guide bone, enhancing the osteoconductive properties of the scaffolds. Finally, Chapter 7 summarises all the work carried out in this thesis to transfer the 3D printing technology of synthetic bone grafts to the market, turning it into a commercially available product.L'ús d'empelts ossis és cada vegada més freqüent: l'os és el segon teixit més trasplantat del món, després de la sang. Per això, aquesta pràctica atreu un gran interès tant a nivell de recerca com per a la indústria biomèdica. En casos en què els defectes són massa grossos o complexos, l'ús d'empelts ossis és essencial per aconseguir una bona regeneració. Malgrat que els autoempelts segueixen sent el tractament de primera elecció, la seva disponibilitat limitada així com la morbiditat associada fan necessari buscar altres solucions. Els empelts sintètics sorgeixen com una alternativa prometedora, donada la seva àmplia disponibilitat i la possibilitat de modificar-ne l'estructura i la composició per obtenir un rendiment òptim. En aquesta tesi s'estudia la hidroxiapatita biomimètica deficient en calci (CDHA) per a la fabricació d'empelts ossis sintètics, des d'una perspectiva orientada a la recerca translacional. S'estudien dues presentacions diferents del producte: una configuració en forma de grànuls i un format personalitzat obtingut per impressió 3D. El Capítol 1 recull una descripció general de la biologia de l'os, juntament amb l'estat de l'art de les diferents estratègies d'empelts ossis que es poden trobar a la literatura. El Capítol 2 se centra en l'estudi de la resposta in vivo de grànuls de CDHA, en comparació amb el xenoempelt boví amb més reconeixement mèdic, en una indicació dental en porcs en miniatura. L'estudi conclou que ambdós biomaterials compleixen els requisits d'un empelt ossi, i.e., biocompatibilitat, osteointegració i osteoconducció. A més, es demostra que la morfologia dels grànuls és un factor clau per assegurar la preservació del volum empeltat. En el Capítol 3 s'investiguen diferents processos per accelerar la consolidació dels empelts impresos en 3D per tal d'aconseguir una tecnologia més adient per a aplicacions industrials, i es desenvolupa un tractament hidrotèrmic que redueix el temps de reacció dels 7 dies necessaris per mètodes biomimètics a només 30 minuts. Amb el nou tractament s'observen petites diferències en les propietats fisicoquímiques (per exemple, en la microestructura, en la fase cristal·lina, la microporositat o la superfície específica), però els empelts obtinguts permeten l'adhesió i la proliferació de cèl·lules mare de rata, que indica que són una solució viable com a substituts ossis. En el Capítol 4 el procés hidrotèrmic introduït al capítol anterior es compara amb el tractament biomimètic in vivo mitjançant la implantació ortotòpica d'empelts 3D en defectes monocorticals en còndils de conills. Les mostres tractades amb aquest nou procediment, a més de presentar l'excel·lent biocompatibilitat i les propietats osteointegratives i osteoconductives pròpies de la CDHA biomimètica, també mostren una quantitat significativament més gran de teixit ossi neoformat que la seva contrapart. Aquestes diferències s'atribueixen a la major permeabilitat de la microestructura, tal com es demostra en un assaig d'absorció de proteïnes. En el Capítol 5 s'estudia una estratègia per millorar tant el grau de concavitat com la superfície específica d'estructures impreses en 3D obtingudes per microextrusió. Per això, s'utilitzen broquets d'extrusió amb seccions transversals no circulars. A més d'aconseguir-ho i caracteritzar les propietats de les estructures impreses, s'identifiquen un conjunt de restriccions tècniques associades a l'ús de broquets no circulars. En un pas més, aquesta estratègia s'aplica a la fabricació d'empelts ossis amb superfícies de filament còncaves i, en el Capítol 6, s'assaja in vivo en un model ortotòpic de còndil de conill. S'observa que utilitzar filaments amb una secció transversal en forma d'estrella ajuda a guiar l'os i millora les propietats osteoconductives dels empelts. Finalment, el Capítol 7 resumeix la feina duta a terme al llarg de la tesi per transferir la tecnologia d'impressió 3D d'empelts ossis sintètics, convertint-lo en un producte disponible comercialment.Postprint (published version