Mathematically defined tissue engineering scaffold architectures prepared by stereolithography

The technologies employed for the preparation of conventional tissue engineering scaffolds restrict the materials choice and the extent to which the architecture can be designed. Here we show the versatility of stereolithography with respect to materials and freedom of design. Porous scaffolds are designed with computer software and built with either a poly(d,l-lactide)-based resin or a poly(d,l-lactide-co-ε-caprolactone)-based resin. Characterisation of the scaffolds by micro-computed tomography shows excellent reproduction of the designs. The mechanical properties are evaluated in compression, and show good agreement with finite element predictions. The mechanical properties of scaffolds can be controlled by the combination of material and scaffold pore architecture. The presented technology and materials enable an accurate preparation of tissue engineering scaffolds with a large freedom of design, and properties ranging from rigid and strong to highly flexible and elastic.

Organ printing

Organ printing techniques offer the potential to produce living 3D tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations along multiple axes with high geometric complexity can be obtained.. The level of control offered by these technologies to develop printed tissues will allow tissue engineers to better study factors that modulate tissue formation and function, and provide a valuable tool to study the effect of anatomy on graft performance. In this chapter we discuss the history behind substrate patterning and cell and organ printing, and the rationale for developing organ printing techniques with respect to limitations of current clinical tissue engineering strategies to effectively repair damaged tissues. We discuss current 2-dimensional and 3-dimesional strategies for assembling cells as well as the necessary support materials such as hydrogels, bioinks and natural and synthetic polymers adopted for organ printing research. Furthermore, given the current state-of-the-art in organ printing technologies, we discuss some of their limitations and provide recommendations for future developments in this rapidly growing field.

Fabrication of osteochondral scaffolds with stereolithography

The osteochondral defect is a classical model for a multiple-tissue problem[1]. Tissue engineering of either bone or cartilage imposes different demands on a scaffold concerning porosity, pore size and interconnectivity. Furthermore, local release of tissue-specific growth factors necessitates a tailored architecture. For the fabrication of an osteochondral scaffold with region specific architecture, an advanced technique is required. Stereolithography is a rapid prototyping technique that allows for the creation of such 3D polymer objects with well-defined architecture. Its working principle is the partial irradiation of a resin, causing a liquid-solid transition. By irradiating this resin by a computer-driven light source, a solid 3D object is constructed layer by layer. To make biodegradable polymers applicable in stereolithography, low-molecular weight polymers have to be functionalised with double bonds to enable photo-initiated crosslinking.

Photo-crosslinking of functionalised lactide oligomers for the fabrication of osteochondral tissue engineering scaffolds

In the fabrication of osteochondral tissue engineering scaffolds, the two distinct tissues impose different requirements on the architecture. Stereo-lithography is a rapid prototyping method that can be utilised to make 3D constructs with high spatial control by radical photopolymerization. In this study, biodegradable resins are developed that can be applied in stereo-lithography. Photo-crosslinked poly(lactide) networks with varying physical properties were synthesised, and by photo polymerizing in the presence of leachable particles porous scaffolds could be prepared as well.

Functional status, postural stability and falls among older adults with glaucoma

Visual impairment is an important contributing factor in falls among older adults, which is one of the leading causes of injury and injury-related death in this population. Visual impairment is also associated with greater disability among older adults, including poorer health-related quality of life, increased frailty and reduced postural stability. The majority of this evidence, however, is based on measures of central visual function, rather than peripheral visual function. As such, there is comparatively limited research on the associations between peripheral visual function, disability and falls, and even fewer studies involving older adults with specific diseases which affect peripheral visual function, the most common of which is glaucoma. Glaucoma is one of the leading causes of irreversible vision loss among older adults, affecting around 3 per cent of adults aged over 60 years. The condition is characterised by retinal nerve fibre loss, primarily affecting peripheral visual function. Importantly, the number of older adults with glaucomatous visual impairment is projected to increase as the ageing population grows. The first component of the thesis examined the cross-sectional association between glaucomatous visual impairment and health-related quality of life (Study 1a), functional status (Study 1b) and postural stability (Study 1c) among older adults. A cohort of 74 community-dwelling adults with glaucoma (mean age 74.2 ± 5.9 years) was recruited and completed a baseline assessment. A number of visual function measures was assessed, including central visual function (visual acuity and contrast sensitivity), motion sensitivity, retinal nerve fibre analysis and monocular and binocular visual field measures (monocular 24-2 and binocular integrated visual fields (IVF): IVF-60 and IVF-120). The analyses focused on the associations between the outcomes measures and severity and location of visual field loss, as this is the primary visual function affected by glaucoma. In Study 1a, we examined the association between visual field loss and health-related quality of life, measured by the Short Form 36-item Health Survey (SF-36). Greater binocular visual field loss, on both IVF measures, was associated with lower SF-36 physical component scores, adjusted for age and gender (Pearson's r =|0.32| to |0.36|, p<0.001). Furthermore, inferior visual field loss was more strongly associated with the SF-36 physical component than superior field loss. No association was found between visual field loss and SF-36 mental component scores. The association between visual field loss and functional status was examined in Study 1b. Functional status outcomes measures included a physical activity questionnaire (Physical Activity Scale for the Elderly, PASE), performance tests (six-minute walk test, timed up and go test and lower leg strength) and an overall functional status score. Significant, but weak, correlations were found between binocular visual field loss and PASE and overall functional status scores, adjusted for age and gender (Pearson's r =|0.24| to |0.33|, p<0.05). Greater inferior visual field loss, independent of superior visual field loss, was significantly associated with poorer physical performance results and lower overall functional status scores. In Study 1c, we examined the association between visual field loss and postural stability, using a swaymeter device which recorded body movement during four conditions: eyes open and closed, on a firm and foam surface. Greater binocular visual field loss was associated with increased postural sway, both on firm and foam surfaces, independent of age and gender (Pearson’s r =|0.44| to |0.46|, p <0.001). Furthermore, inferior visual field was a stronger contributor to postural stability, more so than the superior visual field, particularly on the foam condition with the eyes open. Greater visual field loss was associated with a reduction in the visual contribution to postural sway, which underlies the observed association with postural sway. The second component of the thesis examined the association between severity and location of visual field loss and falls during a 12-month longitudinal follow-up. The number of falls was assessed prospectively using monthly fall calendars. Of the 71 participants who successfully completed the follow up (mean age 73.9 ± 5.7 years), 44% reported one or more falls, and around 20% reported two or more falls. After adjusting for age and gender, every 10 points missed on the IVF-120 increased the rate of falls by 25% (rate ratio 1.25, 95% confidence interval 1.08 - 1.44) or every 5dB reduction in IVF-60 increased the rate of falls by 47% (rate ratio 1.47, 95% confidence interval 1.16 - 1.87). Inferior visual field loss was a significant predictor of falls, more so than superior field loss, highlighting the importance of the inferior visual field area in safe and efficient navigation. Further analyses indicated that postural stability, more so than functional status, may be a potential mediating factor in the relationship between visual field loss and falls. Future research is required to confirm this causal pathway. In addition, the use of topical beta-blocker medications was not associated with an increased rate of falls in this cohort, compared with the use of other topical anti-glaucoma medications. In summary, greater binocular visual field loss among older adults with glaucoma was associated with poorer health-related quality of life in the physical domain, reduced functional status, greater postural instability and higher rates of falling. When the location of visual field loss was examined, inferior visual field loss was consistently more strongly associated with these outcomes than superior visual field loss. Insights gained from this research improve our understanding of the association between glaucomatous visual field loss and disability, and its link with falls among older adults. The clinical implications of this research include the need to include visual field screening in falls risk assessments among older adults and to raise awareness of these findings to eye care practitioners and adults with glaucoma. The findings also assist in developing further research to examine strategies to reduce disability and prevent falls among older adults with glaucoma to promote healthy ageing and independence for these individuals.

Designed tissue engineering scaffolds prepared by stereolithography

For the fabrication of tissue engineering scaffolds, the intended tissue formation process imposes requirements on the architecture. The chosen porosity often is a tradeoff between volume and surface area accessible to cells, and mechanical properties of the construct. Interconnectivity of the pores is essential for cell migration through the scaffold and for mass transport. Conventional techniques such as salt leaching often result in heterogeneous structures and do not allow for a precise control of the architecture. Stereolithography is a rapid prototyping method that can be utilised to make 3D constructs with high spatial control by radical photopolymerisation. In this study, a regular structure based on cyclic repetition of cell units were designed through CAD modelling.. One of these structures was built on a stereolithography apparatus (SLA). Furthermore, a polylactide-based resin was developed that can be applied in stereolithography. Polylactide has proven before to be a well-performing polymer in bone tissue engineering. The final objective in this study is to build newly designed PDLLA scaffolds with a precise SLA fabrication technique to study the effect of scaffold architecture on mechanical and biological properties.

Development of a PDLLA-based stereolithography resin for making tissue engineering scaffolds

The use of porous structures as tissue engineering scaffolds imposes high demands on the pore architecture. Stereolithography is a rapid prototyping method based on photo-polymerisation, that can be utilised to make 3D constructs with high spatial control. In this study, biodegradable resins were developed that can find application in stereolithography. Poly(D,L-lactide) (PDLLA) oligomers were synthesised and functionalised with methacrylate end-groups. By mixing the resulting macromers with a diluent, photo-initiator and inhibitor, lowviscosity resins were obtained that were photocrosslinked to yield stiff and strong degradable poly(lactide) networks. Also, porous scaffolds were fabricated on a stereolithography apparatus (SLA) from a nondegradable resin.

Properties of porous structures prepared by stereolithography using a polylactide resin

Rapid prototyping techniques such as stereolithography allow for building designed tissue engineering scaffolds with high accuracy. In this work, a stereolithography resin based on poly(D,L-lactide) was developed. Biodegradable scaffolds with varying porosity were built from this resin. The scaffolds were analysed by μCT-scanning and compression testing. The porous structures showed excellent mechanical properties in the range of trabecular bone.

Properties of photo-cured poly(D,L-lactide) networks

Poly(D,L-lactide) is a degradable polymer with a long history of use in medical applications. It is strong and stiff and degrades over the course of months into lactic acid, a body-own substance. In the field of tissue engineering it is commonly used to fabricate scaffolds. Stereolithography is a high resolution rapid prototyping technique by which designed 3D objects can be built using photo-initiated radical polymerisations. Poly(D,Llactide) (PDLLA) networks can be obtained by photopolymerisation of oligomers functionalised with unsaturated groups. In this work, PDLLA oligomers of varying architectures (arm lengths, numbers of arms) were synthesised and end-functionalised with methacrylate groups. These macromers were photo-crosslinked in solution to yield PDLLA networks of different architectures. The influence of the network architecture on its physical properties was studied.

Designing participation : Reconsidering agile ridesharing with evolutionary distributed design thinking

This paper explores design thinking from the perspective of designing new forms of interaction to engage people in community change initiatives. A case study of an agile ridesharing system is presented. We describe the fundamental premise of the design approach taken—deploying simple interactive prototypes for use by communities in order to test the design hypothesis, evolve the design in use and grow the community of participants. Real-time use data and feedback from participants influences our understanding of the design approach and feeds into the gradual evolution of the prototype while it continues to be used. We then reflect upon this form of evolutionary distributed design thinking. In contrast to the conventional IT wisdom of building systems to automate ride matching and fare calculation using structured forms, our initial phase of design revealed a preference for informal messaging, negotiation and caution in the sharing of specific location information.

Three-dimensional printing of hierarchical and tough mesoporous bioactive glass scaffolds with a controllable pore architecture, excellent mechanical strength and mineralization ability

New-generation biomaterials for bone regenerations should be highly bioactive, resorbable and mechanically strong. Mesoporous bioactive glass (MBG), as a novel bioactive material, has been used for the study of bone regeneration due to its excellent bioactivity, degradation and drug-delivery ability; however, how to construct a 3D MBG scaffold (including other bioactive inorganic scaffolds) for bone regeneration still maintains a significant challenge due to its/their inherit brittleness and low strength. In this brief communication, we reported a new facile method to prepare hierarchical and multifunctional MBG scaffolds with controllable pore architecture, excellent mechanical strength and mineralization ability for bone regeneration application by a modified 3D-printing technique using polyvinylalcohol (PVA), as a binder. The method provides a new way to solve the commonly existing issues for inorganic scaffold materials, for example, uncontrollable pore architecture, low strength, high brittleness and the requirement for the second sintering at high temperature. The obtained 3D-printing MBG scaffolds possess a high mechanical strength which is about 200 times for that of traditional polyurethane foam template-resulted MBG scaffolds. They have highly controllable pore architecture, excellent apatite-mineralization ability and sustained drug-delivery property. Our study indicates that the 3D-printed MBG scaffolds may be an excellent candidate for bone regeneration.

Hylaluronan-based heparin-incorporated hydrogels for generation of axially vascularized bioartificial bone tissues : in vitro and in vivo evaluation in a PLDLLA-TCP-PCL-composite system

Smart matrices are required in bone tissueengineered grafts that provide an optimal environment for cells and retain osteo-inductive factors for sustained biological activity. We hypothesized that a slow-degrading heparin-incorporated hyaluronan (HA) hydrogel can preserve BMP-2; while an arterio–venous (A–V) loop can support axial vascularization to provide nutrition for a bioartificial bone graft. HA was evaluated for osteoblast growth and BMP-2 release. Porous PLDLLA–TCP–PCL scaffolds were produced by rapid prototyping technology and applied in vivo along with HA-hydrogel, loaded with either primary osteoblasts or BMP-2. A microsurgically created A–V loop was placed around the scaffold, encased in an isolation chamber in Lewis rats. HA-hydrogel supported growth of osteoblasts over 8 weeks and allowed sustained release of BMP-2 over 35 days. The A–V loop provided an angiogenic stimulus with the formation of vascularized tissue in the scaffolds. Bone-specific genes were detected by real time RT-PCR after 8 weeks. However, no significant amount of bone was observed histologically. The heterotopic isolation chamber in combination with absent biomechanical stimulation might explain the insufficient bone formation despite adequate expression of bone-related genes. Optimization of the interplay of osteogenic cells and osteo-inductive factors might eventually generate sufficient amounts of axially vascularized bone grafts for reconstructive surgery.

Pyktree : a K-tree implementation in Python

In this paper we present pyktree, an implementation of the K-tree algorithm in the Python programming language. The K-tree algorithm provides highly balanced search trees for vector quantization that scales up to very large data sets. Pyktree is highly modular and well suited for rapid-prototyping of novel distance measures and centroid representations. It is easy to install and provides a python package for library use as well as command line tools.

The sun gives without ever receiving

YEAR: 2010 ROLE: Artist FORMAT: Miniature 3D Sculpture produced in resin using 3D printing technologies. WITH: International Touring Show ‘Inside Out’ WHAT: A miniature sculpture that contributes towards my ongoing explorations into how our collective ability to sustain (the future) is as much a cultural problematic as it is an economic or technological one. OVERVIEW: The curatorial brief was for each curated artist was to design a piece in CAD suitable for 3D resin printing - The object should be entirely generated through 3D visualisation and modelling tools and should be machined and shipped within the dimensions of 6cm x 6cm x 6cm. My design for this brief was influenced by recent research I had conducted in Mildura in the Sunraysia irrigated region of NW Victoria. Each name set within the work is an Australian soldier/settler – who, on returning from the ‘Great War’ was duly awarded a ‘block’ in Australia’s new inland irrigated settlements - with the explicit task of clearing it to plant and reap. Through their concerted and well-intentioned efforts, these workers began to profoundly re-shape Australia’s marginal country - inadvertently presaging the bleak future faced today by many of Australia’s inland lands and river systems. Furthermore, through that time's predominant colonial conception of ‘terra nullius’ (this land is unoccupied and therefore free to be claimed) they each played a small but formative part in building the profound cultural divide between land and peoples that still haunts Australia today. THE EXHIBITION: Inside Out is a compelling international touring exhibition featuring forty-six miniature sculptures produced in resin using 3D printing technologies. Developments in virtual computer visualisation and integrated digital technologies are giving contemporary makers new insight and opportunities to create objects and forms which were previously impossible to produce or difficult to envisage. The exhibition is the result of collaboration between the Art Technology Coalition, the University of Technology Sydney and RMIT University in Australia along with De Montfort University, Manchester Metropolitan University and Dartington College of Arts at University College Falmouth in the United Kingdom.