Design and characterisation of scaffolds for osteochondral regeneration

Treatment of joint diseases such as osteoarthritis is difficult and requires extensive developments for adequate solutions to emerge. Continued innovation in projects explored in this thesis may be beneficial to understanding the requirements of the joint environment. This may then lead to constructs that perform desirably from both mechanical and biological standpoints, resulting in complete, tissue-engineered osteochondral solutions. This thesis investigated specific scaffold designs for bone and osteochondral tissue engineering, as well as the formation of complex criteria on which cartilage hydrogel scaffolds may be assessed. The combination of hydrogels and ceramics were found to maintain chondrogenesis, while the concentration of photoinitiators in photocrosslinkable hydrogel systems may be optimised to maximise mechanical properties and cell viability. Finally, viscoelasticity of hydrogel blends was assessed using oscillatory motion, demonstrating the property is tailorable.

Computer aided design and finite element modeling to predict bulk mechanical properties of bone scaffolds using triply periodic minimal surfaces (progettazione assistita al calcolatore ed analisi con il metodo degli elementi finiti per predire il comportamento meccanico di scaffolds ossei creati con l'uso di superfici minime periodiche in tre direzioni)

The aim of Tissue Engineering is to develop biological substitutes that will restore lost morphological and functional features of diseased or damaged portions of organs. Recently computer-aided technology has received considerable attention in the area of tissue engineering and the advance of additive manufacture (AM) techniques has significantly improved control over the pore network architecture of tissue engineering scaffolds. To regenerate tissues more efficiently, an ideal scaffold should have appropriate porosity and pore structure. More sophisticated porous configurations with higher architectures of the pore network and scaffolding structures that mimic the intricate architecture and complexity of native organs and tissues are then required. This study adopts a macro-structural shape design approach to the production of open porous materials (Titanium foams), which utilizes spatial periodicity as a simple way to generate the models. From among various pore architectures which have been studied, this work simulated pore structure by triply-periodic minimal surfaces (TPMS) for the construction of tissue engineering scaffolds. TPMS are shown to be a versatile source of biomorphic scaffold design. A set of tissue scaffolds using the TPMS-based unit cell libraries was designed. TPMS-based Titanium foams were meant to be printed three dimensional with the relative predicted geometry, microstructure and consequently mechanical properties. Trough a finite element analysis (FEA) the mechanical properties of the designed scaffolds were determined in compression and analyzed in terms of their porosity and assemblies of unit cells. The purpose of this work was to investigate the mechanical performance of TPMS models trying to understand the best compromise between mechanical and geometrical requirements of the scaffolds. The intention was to predict the structural modulus in open porous materials via structural design of interconnected three-dimensional lattices, hence optimising geometrical properties. With the aid of FEA results, it is expected that the effective mechanical properties for the TPMS-based scaffold units can be used to design optimized scaffolds for tissue engineering applications. Regardless of the influence of fabrication method, it is desirable to calculate scaffold properties so that the effect of these properties on tissue regeneration may be better understood.

Simultaneous optimisation of structural topology and material grading using level set method

Peer reviewed

Additive tissue manufacturing for breast reconstruction: Combining CAD/CAM with adipose tissue engineering

The primary aim of this multidisciplinary project was to develop a new generation of breast implants. Disrupting the currently prevailing paradigm of silicone implants which permanently introduce a foreign body into mastectomy patients, highly porous implants developed as part of this PhD project are biodegradable by the body and augment the growth of natural tissue. Our technology platform leverages computer-assisted-design which allows us to manufacture fully patient-specific implants based on a personalised medicine approach. Multiple animal studies conducted in this project have shown that the polymeric implant slowly degrades within the body harmlessly while the body's own tissue forms concurrently.

Strength of lime-fly ash compacts using different curing techniques and gypsum additive

Lime-fly ash mixtures are exploited for the manufacture of fly ash bricks finding applications in load bearing masonry. Lime-pozzolana reactions take place at a slow pace under ambient temperature conditions and hence very long curing durations are required to achieve meaningful strength values. The present investigation examines the improvements in strength development in lime-fly ash compacts through low temperature steam curing and use of additives like gypsum. Results of density-strength-moulding water content relationships, influence of lime-fly ash ratio, steam curing and role of gypsum on strength development, and characteristics of compacted lime-fly ash-gypsum bricks have been discussed. The test results reveal that (a) strength increases with increase in density irrespective of lime content, type of curing and moulding water content, (b) optimum lime-fly ash ratio yielding maximum strength is about 0.75 in the normal curing conditions, (c) 24 h of steam curing (at 80A degrees C) is sufficient to achieve nearly possible maximum strength, (d) optimum gypsum content yielding maximum compressive strength is at 2%, (e) with gypsum additive it is possible to obtain lime-fly ash bricks or blocks having sufficient strength (> 10 MPa) at 28 days of normal wet burlap curing.

Modellgestützte und hierarchische Prozesskettenbetrachtung für die additive Fertigung

Additive Fertigungsverfahren eignen sich für die wirtschaftliche Herstellung von Bauteilen im Bereich kleiner bis mittlerer Stückzahlen, da keine Formen oder Spezialwerkzeuge notwendig sind. Die erzielbaren Eigenschaften sind oftmals bereits ausreichend, um einen Einsatz auch in Serienanwendungen zu ermöglichen. Verbunden mit den Vorteilen der Technologie bezüglich einer hohen Flexibilität, sowohl während der Konstruktion als auch der Fertigung, können sich durch eine konsequente Nutzung finanzielle Einsparmöglichkeiten entlang des gesamten Produktlebenszyklus ergeben. Bezüglich der Wirtschaftlichkeit der Verfahren herrscht oftmals noch Unklarheit, da geeignete Methoden fehlen, um diese zu bewerten. Bestehende Methoden und Werkzeuge zur Bewertung der Wirtschaftlichkeit konventioneller Fertigungsverfahren sind dabei für die additive Fertigung nicht direkt nutzbar. In dem Artikel wird eine Methode zur modellgestützten Abbildung einer gesamten additiven Fertigungskette vorgestellt, welche auch die Wechselwirkungen zwischen den einzelnen Prozesskettengliedern berücksichtigen soll. Eine konkrete Aussage bezüglich der Wirtschaftlichkeit der additiven Fertigung soll somit ermöglicht werden.

Rapid prototyping of multi-scale biomedical microdevices by combining additive manufacturing technologies

The possibility of designing and manufacturing biomedical microdevices with multiple length-scale geometries can help to promote special interactions both with their environment and with surrounding biological systems. These interactions aim to enhance biocompatibility and overall performance by using biomimetic approaches. In this paper, we present a design and manufacturing procedure for obtaining multi-scale biomedical microsystems based on the combination of two additive manufacturing processes: a conventional laser writer to manufacture the overall device structure, and a direct-laser writer based on two-photon polymerization to yield finer details. The process excels for its versatility, accuracy and manufacturing speed and allows for the manufacture of microsystems and implants with overall sizes up to several millimeters and with details down to sub-micrometric structures. As an application example we have focused on manufacturing a biomedical microsystem to analyze the impact of microtextured surfaces on cell motility. This process yielded a relevant increase in precision and manufacturing speed when compared with more conventional rapid prototyping procedures.

Accuracy of computer-aided design/computer-assisted manufacture (CAD/CAM) fabricated dental restorations: a comparative study

Introduction: Computer-Aided-Design (CAD) and Computer-Aided-Manufacture (CAM) has been developed to fabricate fixed dental restorations accurately, faster and improve cost effectiveness of manufacture when compared to the conventional method. Two main methods exist in dental CAD/CAM technology: the subtractive and additive methods. While fitting accuracy of both methods has been explored, no study yet has compared the fabricated restoration (CAM output) to its CAD in terms of accuracy. The aim of this present study was to compare the output of various dental CAM routes to a sole initial CAD and establish the accuracy of fabrication. The internal fit of the various CAM routes were also investigated. The null hypotheses tested were: 1) no significant differences observed between the CAM output to the CAD and 2) no significant differences observed between the various CAM routes. Methods: An aluminium master model of a standard premolar preparation was scanned with a contact dental scanner (Incise, Renishaw, UK). A single CAD was created on the scanned master model (InciseCAD software, V2.5.0.140, UK). Twenty copings were then fabricated by sending the single CAD to a multitude of CAM routes. The copings were grouped (n=5) as: Laser sintered CoCrMo (LS), 5-axis milled CoCrMo (MCoCrMo), 3-axis milled zirconia (ZAx3) and 4-axis milled zirconia (ZAx4). All copings were micro-CT scanned (Phoenix X-Ray, Nanotom-S, Germany, power: 155kV, current: 60µA, 3600 projections) to produce 3-Dimensional (3D) models. A novel methodology was created to superimpose the micro-CT scans with the CAD (GOM Inspect software, V7.5SR2, Germany) to indicate inaccuracies in manufacturing. The accuracy in terms of coping volume was explored. The distances from the surfaces of the micro-CT 3D models to the surfaces of the CAD model (CAD Deviation) were investigated after creating surface colour deviation maps. Localised digital sections of the deviations (Occlusal, Axial and Cervical) and selected focussed areas were then quantitatively measured using software (GOM Inspect software, Germany). A novel methodology was also explored to digitally align (Rhino software, V5, USA) the micro-CT scans with the master model to investigate internal fit. Fifty digital cross sections of the aligned scans were created. Point-to-point distances were measured at 5 levels at each cross section. The five levels were: Vertical Marginal Fit (VF), Absolute Marginal Fit (AM), Axio-margin Fit (AMF), Axial Fit (AF) and Occlusal Fit (OF). Results: The results of the volume measurement were summarised as: VM-CoCrMo (62.8mm3 ) > VZax3 (59.4mm3 ) > VCAD (57mm3 ) > VZax4 (56.1mm3 ) > VLS (52.5mm3 ) and were all significantly different (p presented as areas with different colour. No significant differences were observed at the internal aspect of the cervical aspect between all groups of copings. Significant differences (p< M-CoCrMo Internal Occlusal, Internal Axial and External Axial 2 ZAx3 > ZAx4 External Occlusal, External Cervical 3 ZAx3 < ZAx4 Internal Occlusal 4 M-CoCrMo > ZAx4 Internal Occlusal and Internal Axial The mean values of AMF and AF were significantly (p M-CoCrMo and CAD > ZAx4. Only VF of M-CoCrMo was comparable with the CAD Internal Fit. All VF and AM values were within the clinically acceptable fit (120µm). Conclusion: The investigated CAM methods reproduced the CAD accurately at the internal cervical aspect of the copings. However, localised deviations at axial and occlusal aspects of the copings may suggest the need for modifications in these areas prior to fitting and veneering with porcelain. The CAM groups evaluated also showed different levels of Internal Fit thus rejecting the null hypotheses. The novel non-destructive methodologies for CAD/CAM accuracy and internal fit testing presented in this thesis may be a useful evaluation tool for similar applications.

Mixing performance evaluation of additive manufactured milli-scale reactors

The mixing performance of three passive milli-scale reactors with different geometries was investigated at different Reynolds numbers. The effects of design and operating characteristics such as mixing channel shape and volume flow rate were investigated. The main objective of this work was to demonstrate a process design method that uses on Computational Fluid Dynamics (CFD) for modeling and Additive Manufacturing (AM) technology for manufacture. The reactors were designed and simulated using SolidWorks and Fluent 15.0 software, respectively. Manufacturing of the devices was performed with an EOS M-series AM system. Step response experiments with distilled Millipore water and sodium hydroxide solution provided time-dependent concentration profiles. Villermaux-Dushman reaction experiments were also conducted for additional verification of CFD results and for mixing efficiency evaluation of the different geometries. Time-dependent concentration data and reaction evaluation showed that the performance of the AM-manufactured reactors matched the CFD results reasonably well. The proposed design method allows the implementation of new and innovative solutions, especially in the process design phase, for industrial scale reactor technologies. In addition, rapid implementation is another advantage due to the virtual flow design and due to the fast manufacturing which uses the same geometric file formats.