Publications by authors named "Maria A Woodruff"

52 Publications

Frugal 3D scanning using smartphones provides an accessible framework for capturing the external ear.

J Plast Reconstr Aesthet Surg 2021 May 3. Epub 2021 May 3.

Queensland University of Technology (QUT), Brisbane, Queensland, 4000, Australia.

Three-dimensional (3D) scanning technologies, such as medical imaging and surface scanning, have important applications for capturing patient anatomy to create personalised prosthetics. Digital approaches for capturing anatomical detail as opposed to traditional, invasive impression techniques significantly reduces turnaround times and lower production costs while still maintaining the high aesthetic quality of the end product. While previous case studies utilise expensive 3D scanning and modelling frameworks, their clinical translation is limited due to high equipment costs. In this study, we develop and validate a low-cost framework for clinical 3D scanning of the external ear using photogrammetry and a smartphone camera. We recruited five novice operators who watched an instructional video before scanning 20 healthy adult participant ears who did not have microtia. Our results show that the smartphone-based photogrammetry methodology produces 3D scans of the external ear that were accurate to (1.5 ± 0.4) mm and were (71 ± 14) % complete compared with those from a gold standard reference scanner, with no significant difference observed between operators. A moderate to strong interrater reliability was determined for all novice operators, suggesting that all novice operators were able to capture repeatable scans. The development of this smartphone photogrammetry approach has the potential to provide a non-invasive, inexpensive and accessible means to capture patient morphology for use in clinical assessment and personalised device manufacture, specifically for ear prostheses. We also demonstrate that inexperienced operators can rapidly learn and apply smartphone photogrammetry for accurate and reliable scans of the external ear with important applications for future clinical translation.
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http://dx.doi.org/10.1016/j.bjps.2021.03.131DOI Listing
May 2021

3D Printing Improved Testicular Prostheses: Using Lattice Infill Structure to Modify Mechanical Properties.

Front Surg 2021 20;8:626143. Epub 2021 Apr 20.

Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia.

Patients often opt for implantation of testicular prostheses following orchidectomy for cancer or torsion. Recipients of testicular prostheses report issues regarding firmness, shape, size, and position, aspects of which relate to current limitations of silicone materials used and manufacturing methods for soft prostheses. We aim to create a 3D printable testicular prosthesis which mimics the natural shape and stiffness of a human testicle using a lattice infill structure. Porous testicular prostheses were engineered with relative densities from 0.1 to 0.9 using a repeating cubic unit cell lattice inside an anatomically accurate testicle 3D model. These models were printed using a multi-jetting process with an elastomeric material and compared with current market prostheses using shore hardness tests. Additionally, standard sized porous specimens were printed for compression testing to verify and match the stiffness to human testicle elastic modulus (E-modulus) values from literature. The resulting 3D printed testicular prosthesis of relative density between 0.3 and 0.4 successfully achieved a reduction of its bulk compressive E-modulus from 360 KPa to a human testicle at 28 Kpa. Additionally, this is the first study to quantitatively show that current commercial testicular prostheses are too firm compared to native tissue. 3D printing allows us to create metamaterials that match the properties of human tissue to create customisable patient specific prostheses. This method expands the use cases for existing biomaterials by tuning their properties and could be applied to other implants mimicking native tissues.
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http://dx.doi.org/10.3389/fsurg.2021.626143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093764PMC
April 2021

Detection of clustered anomalies in single-voxel morphometry as a rapid automated method for identifying intracranial aneurysms.

Comput Med Imaging Graph 2021 Apr 25;89:101888. Epub 2021 Feb 25.

Queensland University of Technology (QUT), Contact Lens and Visual Optics Laboratory, Centre for Vision and Eye Research, School of Optometry and Vision Science, Kelvin Grove, QLD, 4059, Australia.

Unruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to cause a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of UIAs exist undiscovered until rupture. Current clinical practice in the detection of UIAs relies heavily on manual radiological review of standard imaging modalities. Recent computer-aided UIA diagnoses can sensitively detect and measure UIAs within cranial angiograms but remain limited to low specificities whose output also requires considerable radiologist interpretation not amenable to broad screening efforts. To address these limitations, we have developed a novel automatic pipeline algorithm which inputs medical images and outputs detected UIAs by characterising single-voxel morphometry of segmented neurovasculature. Once neurovascular anatomy of a specified resolution is segmented, correlations between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 min on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities.
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http://dx.doi.org/10.1016/j.compmedimag.2021.101888DOI Listing
April 2021

Rapid Segmentation of Renal Tumours to Calculate Volume Using 3D Interpolation.

J Digit Imaging 2021 Feb 9. Epub 2021 Feb 9.

Department of Urology, Redcliffe Hospital, Redcliffe, QLD, Australia.

Small renal masses are commonly diagnosed with modern medical imaging. Renal tumour volume has been explored as a prognostic tool to help decide when intervention is needed and appears to provide additional prognostic information for smaller tumours compared with tumour diameter. However, the current method of calculating tumour volume in clinical practice uses the ellipsoid equation (π/6 × length × width × height) which is an oversimplified approach. Some research groups trace the contour of the tumour in every image slice which is impractical for clinical use. In this study, we demonstrate a method of using 3D segmentation software and the 3D interpolation method to rapidly calculate renal tumour volume in under a minute. Using this method in 27 patients that underwent radical or partial nephrectomy, we found a 10.07% mean absolute difference compared with the traditional ellipsoid method. Our segmentation volume was closer to the calculated histopathological tumour volume than the traditional method (p = 0.03) with higher Lin's concordance correlation coefficient (0.79 vs 0.72). 3D segmentation has many uses related to 3D printing and modelling and is becoming increasingly common. Calculation of tumour volume is one additional benefit it provides. Further studies on the association between segmented tumour volume and prognosis are needed.
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http://dx.doi.org/10.1007/s10278-020-00416-zDOI Listing
February 2021

Guidelines for establishing a 3-D printing biofabrication laboratory.

Biotechnol Adv 2020 12 27;45:107652. Epub 2020 Oct 27.

School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287, USA. Electronic address:

Advanced manufacturing and 3D printing are transformative technologies currently undergoing rapid adoption in healthcare, a traditionally non-manufacturing sector. Recent development in this field, largely enabled by merging different disciplines, has led to important clinical applications from anatomical models to regenerative bioscaffolding and devices. Although much research to-date has focussed on materials, designs, processes, and products, little attention has been given to the design and requirements of facilities for enabling clinically relevant biofabrication solutions. These facilities are critical to overcoming the major hurdles to clinical translation, including solving important issues such as reproducibility, quality control, regulations, and commercialization. To improve process uniformity and ensure consistent development and production, large-scale manufacturing of engineered tissues and organs will require standardized facilities, equipment, qualification processes, automation, and information systems. This review presents current and forward-thinking guidelines to help design biofabrication laboratories engaged in engineering model and tissue constructs for therapeutic and non-therapeutic applications.
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http://dx.doi.org/10.1016/j.biotechadv.2020.107652DOI Listing
December 2020

Development of Mechanically Enhanced Polycaprolactone Composites by a Functionalized Titanate Nanofiller for Melt Electrowriting in 3D Printing.

ACS Appl Mater Interfaces 2020 Oct 12;12(42):47993-48006. Epub 2020 Oct 12.

School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, Queensland 4001, Australia.

Three-dimensional (3D) printing technologies are widely applied in various industries and research fields and are currently the subject of intensive investigation and development. However, high-performance materials that are suitable for 3D printing are still in short supply, which is a major limitation for 3D printing, particularly for biomedical applications. The physicochemical properties of single constituent materials may not be sufficient to meet the needs of modern biotechnology development and production. To enhance the materials' performance and broaden their applications, this work designed and tested a series of titanate nanofiller (nanowire and nanotube)-enhanced polycaprolactone (PCL) composites that were 3D-printable and provided superior mechanical properties. By grafting two different functional groups (phenyl- and thiol-terminated ligands), the nanofiller surface showed improved hydrophobicity, which significantly improved their dispersion in the PCL matrix. After characterizing the surface modification, we evaluated the significance of the homogeneity of the ceramic nanofiller in terms of printability, formability, and mechanical strength. Melt electrowriting additive manufacturing was used to fabricate microfibers of PCL and PCL/nanofiller composites. Improved nanofiller dispersion enabled intact and uniform sample morphology, and in contrast, nanofiller aggregation greatly varied the viscosity during the printing process, which could result in poorly printed structures. Importantly, the modified ceramic/PCL composite delivered enhanced and stable mechanical properties, where its Young's modulus was measured to be 1.67 GPa, which is more than 7 times higher compared to that of pristine PCL (0.22 GPa). Retaining the cell safety properties (comparable to PCL), the concept of enhancing biocompatible polymers with modified nanofillers shows great potential in the field of customized 3D printing for biomedicine.
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http://dx.doi.org/10.1021/acsami.0c14831DOI Listing
October 2020

Past, Present, and Future of Soft-Tissue Prosthetics: Advanced Polymers and Advanced Manufacturing.

Adv Mater 2020 Oct 9;32(42):e2001122. Epub 2020 Sep 9.

School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, 2 George Street, Brisbane, QLD, 4000, Australia.

Millions of people worldwide experience disfigurement due to cancers, congenital defects, or trauma, leading to significant psychological, social, and economic disadvantage. Prosthetics aim to reduce their suffering by restoring aesthetics and function using synthetic materials that mimic the characteristics of native tissue. In the 1900s, natural materials used for thousands of years in prosthetics were replaced by synthetic polymers bringing about significant improvements in fabrication and greater realism and utility. These traditional methods have now been disrupted by the advanced manufacturing revolution, radically changing the materials, methods, and nature of prosthetics. In this report, traditional synthetic polymers and advanced prosthetic materials and manufacturing techniques are discussed, including a focus on prosthetic material degradation. New manufacturing approaches and future technological developments are also discussed in the context of specific tissues requiring aesthetic restoration, such as ear, nose, face, eye, breast, and hand. As advanced manufacturing moves from research into clinical practice, prosthetics can begin new age to significantly improve the quality of life for those suffering tissue loss or disfigurement.
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http://dx.doi.org/10.1002/adma.202001122DOI Listing
October 2020

Variability in accuracy of prostate cancer segmentation among radiologists, urologists, and scientists.

Cancer Med 2020 10 18;9(19):7172-7182. Epub 2020 Aug 18.

Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.

Background: There is increasing research in using segmentation of prostate cancer to create a digital 3D model from magnetic resonance imaging (MRI) scans for purposes of education or surgical planning. However, the variation in segmentation of prostate cancer among users and potential inaccuracy has not been studied.

Methods: Four consultant radiologists, four consultant urologists, four urology trainees, and four nonclinician segmentation scientists were asked to segment a single slice of a lateral T3 prostate tumor on MRI ("Prostate 1"), an anterior zone prostate tumor MRI ("Prostate 2"), and a kidney tumor computed tomography (CT) scan ("Kidney"). Time taken and self-rated subjective accuracy out of a maximum score of 10 were recorded. Root mean square error, Dice coefficient, Matthews correlation coefficient, Jaccard index, specificity, and sensitivity were calculated using the radiologists as the ground truth.

Results: There was high variance among the radiologists in segmentation of Prostate 1 and 2 tumors with mean Dice coefficients of 0.81 and 0.58, respectively, compared to 0.96 for the kidney tumor. Urologists and urology trainees had similar accuracy, while nonclinicians had the lowest accuracy scores for Prostate 1 and 2 tumors (0.60 and 0.47) but similar for kidney tumor (0.95). Mean sensitivity in Prostate 1 (0.63) and Prostate 2 (0.61) was lower than specificity (0.92 and 0.93) suggesting under-segmentation of tumors in the non-radiologist groups. Participants spent less time on the kidney tumor segmentation and self-rated accuracy was higher than both prostate tumors.

Conclusion: Segmentation of prostate cancers is more difficult than other anatomy such as kidney tumors. Less experienced participants appear to under-segment models and underestimate the size of prostate tumors. Segmentation of prostate cancer is highly variable even among radiologists, and 3D modeling for clinical use must be performed with caution. Further work to develop a methodology to maximize segmentation accuracy is needed.
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http://dx.doi.org/10.1002/cam4.3386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541146PMC
October 2020

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size.

Acta Biomater 2020 09 13;114:285-295. Epub 2020 Jul 13.

School of Mathematical Sciences, Queensland University of Technology (QUT), Brisbane, Australia.

Tissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction-diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction-diffusion models of cells that have robust, consistent behaviours.
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http://dx.doi.org/10.1016/j.actbio.2020.07.010DOI Listing
September 2020

An advanced prosthetic manufacturing framework for economic personalised ear prostheses.

Sci Rep 2020 07 10;10(1):11453. Epub 2020 Jul 10.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.

Craniofacial prostheses are commonly used to restore aesthetics for those suffering from malformed, damaged, or missing tissue. Traditional fabrication is costly, uncomfortable for the patient, and laborious; involving several hours of hand-crafting by a prosthetist, with the results highly dependent on their skill level. In this paper, we present an advanced manufacturing framework employing three-dimensional scanning, computer-aided design, and computer-aided manufacturing to efficiently fabricate patient-specific ear prostheses. Three-dimensional scans were taken of ears of six participants using a structured light scanner. These were processed using software to model the prostheses and 3-part negative moulds, which were fabricated on a low-cost desktop 3D printer, and cast with silicone to produce ear prostheses. The average cost was approximately $3 for consumables and $116 for 2 h of labour. An injection method with smoothed 3D printed ABS moulds was also developed at a cost of approximately $155 for consumables and labour. This contrasts with traditional hand-crafted prostheses which range from $2,000 to $7,000 and take around 14 to 15 h of labour. This advanced manufacturing framework provides potential for non-invasive, low cost, and high-accuracy alternative to current techniques, is easily translatable to other prostheses, and has potential for further cost reduction.
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http://dx.doi.org/10.1038/s41598-020-67945-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351946PMC
July 2020

Three-dimensional printing versus conventional machining in the creation of a meatal urethral dilator: development and mechanical testing.

Biomed Eng Online 2020 Jul 1;19(1):55. Epub 2020 Jul 1.

Science and Engineering Faculty, Queensland University of Technology, Brisbane, Australia.

Background: Three-dimensional (3D) printing is a promising technology, but the limitations are often poorly understood. We compare different 3D printing methods with conventional machining techniques in manufacturing meatal urethral dilators which were recently removed from the Australian market.

Methods: A prototype dilator was 3D printed vertically orientated on a low-cost fused deposition modelling (FDM) 3D printer in polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS). It was also 3D printed horizontally orientated in ABS on a high-end FDM 3D printer with soluble support material, as well as on an SLS 3D printer in medical nylon. The dilator was also machined in stainless steel using a lathe. All dilators were tested mechanically in a custom rig by hanging calibrated weights from the handle until the dilator snapped.

Results: The horizontally printed ABS dilator experienced failure at a greater load than the vertically printed PLA and ABS dilators, respectively (503 g vs 283 g vs 163 g, p < 0.001). The SLS nylon dilator and machined steel dilator did not fail. The steel dilator is the most expensive with a quantity of five at 98 USD each, but this decreases to 30 USD each for a quantity of 1000. In contrast, the cost for the SLS dilator is 33 USD each for five and 27 USD each for 1000.

Conclusions: Low-cost FDM 3D printing is not a replacement for conventional manufacturing. 3D printing is best used for patient-specific parts, prototyping or manufacturing complex parts that have additional functionality that cannot otherwise be achieved.
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http://dx.doi.org/10.1186/s12938-020-00799-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329536PMC
July 2020

Multi-colour extrusion fused deposition modelling: a low-cost 3D printing method for anatomical prostate cancer models.

Sci Rep 2020 06 19;10(1):10004. Epub 2020 Jun 19.

Redcliffe Hospital, Metro North Hospital Health Service, Queensland, Australia.

Three-dimensional (3D) printed prostate cancer models are an emerging adjunct for urological surgical planning and patient education, however published methods are costly which limits their translation into clinical practice. Multi-colour extrusion fused deposition modelling (FDM) can be used to create 3D prostate cancer models of a quality comparable to more expensive techniques at a fraction of the cost. Three different 3D printing methods were used to create the same 3D prostate model: FDM, colour jet printing (CJP) and material jetting (MJ), with a calculated cost per model of USD 20, USD 200 and USD 250 respectively. When taking into account the cost, the FDM prostate models are the most preferred 3D printing method by surgeons. This method could be used to manufacture low-cost 3D printed models across other medical disciplines.
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http://dx.doi.org/10.1038/s41598-020-67082-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305153PMC
June 2020

Advancements in Soft-Tissue Prosthetics Part B: The Chemistry of Imitating Life.

Front Bioeng Biotechnol 2020 23;8:147. Epub 2020 Apr 23.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.

Each year, congenital defects, trauma or cancer often results in considerable physical disfigurement for many people worldwide. This adversely impacts their psychological, social and economic outlook, leading to poor life experiences and negative health outcomes. In many cases of soft tissue disfigurement, highly personalized prostheses are available to restore both aesthetics and function. As discussed in part A of this review, key to the success of any soft tissue prosthetic is the fundamental properties of the materials. This determines the maximum attainable level of aesthetics, attachment mechanisms, fabrication complexity, cost, and robustness. Since the early-mid 20th century, polymers have completely replaced natural materials in prosthetics, with advances in both material properties and fabrication techniques leading to significantly improved capabilities. In part A, we discussed the history of polymers in prosthetics, their ideal properties, and the application of polymers in prostheses for the ear, nose, eye, breast and finger. We also reviewed the latest developments in advanced manufacturing and 3D printing, including different fabrication technologies and new and upcoming materials. In this review, Part B, we detail the chemistry of the most commonly used synthetic polymers in soft tissue prosthetics; silicone, acrylic resin, vinyl polymer, and polyurethane elastomer. For each polymer, we briefly discuss their history before detailing their chemistry and fabrication processes. We also discuss degradation of the polymer in the context of their application in prosthetics, including time and weathering, the impact of skin secretions, microbial growth and cleaning and disinfecting. Although advanced manufacturing promises new fabrication capabilities using exotic synthetic polymers with programmable material properties, silicones and acrylics remain the most commonly used materials in prosthetics today. As research in this field progresses, development of new variations and fabrication techniques based on these synthetic polymers will lead to even better and more robust soft tissue prosthetics, with improved life-like aesthetics and lower cost manufacturing.
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http://dx.doi.org/10.3389/fbioe.2020.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191111PMC
April 2020

Advancements in Soft-Tissue Prosthetics Part A: The Art of Imitating Life.

Front Bioeng Biotechnol 2020 31;8:121. Epub 2020 Mar 31.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.

Physical disfigurement due to congenital defects, trauma, or cancer causes considerable distress and physical impairment for millions of people worldwide; impacting their economic, psychological and social wellbeing. Since 3000 B.C., prosthetic devices have been used to address these issues by restoring both aesthetics and utility to those with disfigurement. Internationally, academic and industry researchers are constantly developing new materials and manufacturing techniques to provide higher quality and lower cost prostheses to those people who need them. New advanced technologies including 3D imaging, modeling, and printing are revolutionizing the way prostheses are now made. These new approaches are disrupting the traditional and manual art form of prosthetic production which are laborious and costly and are being replaced by more precise and quantitative processes which enable the rapid, low cost production of patient-specific prostheses. In this two part review, we provide a comprehensive report of past, present and emerging soft-tissue prosthetic materials and manufacturing techniques. In this review, part A, we examine, historically, the ideal properts of a polymeric material when applied in soft-tissue prosthetics. We also detail new research approaches to target specific tissues which commonly require aesthetic restoration (e.g. ear, nose and eyes) and discuss both traditional and advanced fabrication methods, from hand-crafted impression based approaches to advanced manufactured prosthetics. We discuss the chemistry and related details of most significant synthetic polymers used in soft-tissue prosthetics in Part B. As advanced manufacturing transitions from research into practice, the five millennia history of prosthetics enters a new age of economic, personalized, advanced soft tissue prosthetics and with this comes significantly improved quality of life for the people affected by tissue loss.
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http://dx.doi.org/10.3389/fbioe.2020.00121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145402PMC
March 2020

Design of an Open-Source, Low-Cost Bioink and Food Melt Extrusion 3D Printer.

J Vis Exp 2020 03 2(157). Epub 2020 Mar 2.

Science and Engineering Faculty, Queensland University of Technology (QUT).

Three-dimensional (3D) printing is an increasingly popular manufacturing technique that allows highly complex objects to be fabricated with no retooling costs. This increasing popularity is partly driven by falling barriers to entry such as system set-up costs and ease of operation. The following protocol presents the design and construction of an Additive Manufacturing Melt Extrusion (ADDME) 3D printer for the fabrication of custom parts and components. ADDME has been designed with a combination of 3D-printed, laser-cut, and online-sourced components. The protocol is arranged into easy-to-follow sections, with detailed diagrams and parts lists under the headings of framing, y-axis and bed, x-axis, extrusion, electronics, and software. The performance of ADDME is evaluated through extrusion testing and 3D printing of complex objects using viscous cream, chocolate, and Pluronic F-127 (a model for bioinks). The results indicate that ADDME is a capable platform for the fabrication of materials and constructs for use in a wide range of industries. The combination of detailed diagrams and video content facilitates access to low-cost, easy-to-operate equipment for individuals interested in 3D printing of complex objects from a wide range of materials.
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http://dx.doi.org/10.3791/59834DOI Listing
March 2020

Pre-screening the intrinsic angiogenic capacity of biomaterials in an optimised chorioallantoic membrane model.

J Tissue Eng 2020 Jan-Dec;11:2041731420901621. Epub 2020 Feb 4.

Regenerative Biomaterials Group, RAFT Institute, Mount Vernon Hospital, Northwood, UK.

Biomaterial development for clinical applications is currently on the rise. This necessitates adequate testing, where the structure and composition of biomaterials must be specifically tailored to withstand repair and regeneration responses for a successful clinical outcome. The chorioallantoic membrane of chicken embryos has been previously used to study angiogenesis, a prerequisite for most tissue repair and regeneration. In this study, we report an optimised method using a glass-cling film set-up that yields increased embryo survival rates and has an improved protocol for harvesting biomaterials. Furthermore, we used this method to examine the intrinsic angiogenic capacity of a variety of biomaterials categorised as natural, synthetic, natural/synthetic and natural/natural composites with varying porosities. We detected significant differences in biomaterials' angiogenesis with natural polymers and polymers with a high overall porosity showing a greater vascularisation compared to synthetic polymers. Therefore, our proposed chorioallantoic membrane method can be effectively used to pre-screen biomaterials intended for clinical application.
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http://dx.doi.org/10.1177/2041731420901621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000866PMC
February 2020

Design tools for patient specific and highly controlled melt electrowritten scaffolds.

J Mech Behav Biomed Mater 2020 05 13;105:103695. Epub 2020 Feb 13.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Science and Engineering Faculty, Queensland University of Technology, Brisbane, Australia. Electronic address:

Melt electrowriting (MEW) has grown in popularity in biofabrication research due to its ability to fabricate complex, high-precision networks of fibres. These fibres can mimic the morphology of a natural extracellular matrix, enabling tissue analogues for transplantation or personalised drug screening. To date, MEW has employed two different collector-plate modalities for the fabrication of constructs. Flat collector plates, typical of traditional 3D printing methods, allow for the layer-by-layer fabrication of 2D structures into complex 3D structures. Alternatively, rotating mandrels can be used for the creation of tubular scaffolds. However, unlike other additive manufacturing techniques that can immediately start and stop the extrusion of material during printing, MEW instead requires a continuous flow of polymer. Consequently, conventional g-code control software packages are unsuitable. To overcome this challenge, a suite of customised pattern generation software tools have been developed to enable the design of MEW scaffolds with highly-controlled geometry, including crosshatch, gradient porosity, tubular, and patient-specific configurations. The high level of design control using this approach enables the production of scaffolds with highly adaptable mechanical properties, as well as the potential to influence biological properties for cell attachment and proliferation.
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http://dx.doi.org/10.1016/j.jmbbm.2020.103695DOI Listing
May 2020

Current applications of three-dimensional printing in urology.

BJU Int 2020 01 6;125(1):17-27. Epub 2019 Nov 6.

Redcliffe Hospital, Metro North Hospital and Health Service, Brisbane, Queensland, Australia.

Three-dimensional (3D) printing or additive manufacturing is a new technology that has seen rapid development in recent years with decreasing costs. 3D printing allows the creation of customised, finely detailed constructs. Technological improvements, increased printer availability, decreasing costs, improved cell culture techniques, and biomaterials have enabled complex, novel and individualised medical treatments to be developed. Although the long-term goal of printing biocompatible organs has not yet been achieved, major advances have been made utilising 3D printing in biomedical engineering. In this literature review, we discuss the role of 3D printing in relation to urological surgery. We highlight the common printing methods employed and show examples of clinical urological uses. Currently, 3D printing can be used in urology for education of trainees and patients, surgical planning, creation of urological equipment, and bioprinting. In this review, we summarise the current applications of 3D-printing technology in these areas of urology.
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http://dx.doi.org/10.1111/bju.14928DOI Listing
January 2020

Investigation of Sustained BMP Delivery in the Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ) in a Rat Model.

Macromol Biosci 2019 11 24;19(11):e1900226. Epub 2019 Sep 24.

Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Queensland, 4059, Australia.

Medication-related osteonecrosis of the jaw (MRONJ) poses an ongoing challenge for clinicians and researchers. Currently, there is a lack of preventative measures available for at-risk patients undergoing tooth extractions, especially those with prior bisphosphonate treatment due to osteoporosis or bone metastasis diagnoses. Here, these issues are addressed using a preventative tissue engineering strategy against MRONJ development. This study evaluates the efficacy of a poly(ethylene glycol)-heparin hydrogel as a tool for the delivery of arginylglycylaspartic acid (RGD) and recombinant human bone morphogenic protein-2 (rhBMP-2). Three groups of skeletally mature rats each receive two doses of intravenous zoledronic acid prior to surgery and undergo extraction of the right first mandibular molar with gingival closure. Experimental groups either have the sockets left empty, filled with hydrogel minus rhBMP-2, or filled with hydrogel plus rhBMP-2. Eight weeks postoperatively specimens are analyzed using radiological, histological, and scanning electron microscopy (SEM) techniques. µCT analysis shows increased bone formation with hydrogel/rhBMP-2 delivery compared to the empty socket. Hydrogel-treated groups display increased presence of osteocytes and increased osteoclastic action compared to the empty sockets. These results represent the first step toward improved delivery of rhBMP-2 and a potential MRONJ preventative for patients undergoing bisphosphonate treatment.
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http://dx.doi.org/10.1002/mabi.201900226DOI Listing
November 2019

Spectral changes associated with transmission of OLED emission through human skin.

Sci Rep 2019 07 8;9(1):9875. Epub 2019 Jul 8.

School of Chemistry Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia.

A recent and emerging application of organic light emitting diodes (OLEDs) is in wearable technologies as they are flexible, stretchable and have uniform illumination over a large area. In such applications, transmission of OLED emission through skin is an important part and therefore, understanding spectral changes associated with transmission of OLED emission through human skin is crucial. Here, we report results on transmission of OLED emission through human skin samples for yellow and red emitting OLEDs. We found that the intensity of transmitted light varies depending on the site from where the skin samples are taken. Additionally, we show that the amount of transmitted light reduces by ~ 35-40% when edge emissions from the OLEDs are blocked by a mask exposing only the light emitting area of the OLED. Further, the emission/electroluminescence spectra of the OLEDs widen significantly upon passing through skin and the full width at half maximum increases by >20 nm and >15 nm for yellow and red OLEDs, respectively. For comparison, emission profile and intensities of transmitted light for yellow and red inorganic LEDs are also presented. Our results are highly relevant for the rapidly expanding area of non-invasive wearable technologies that use organic optoelectronic devices for sensing.
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http://dx.doi.org/10.1038/s41598-019-45867-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614498PMC
July 2019

Tissue Morphology and Antigenicity in Mouse and Rat Tibia: Comparing 12 Different Decalcification Conditions.

J Histochem Cytochem 2019 08 15;67(8):545-561. Epub 2019 May 15.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.

Conventional bone decalcification is a time-consuming process and is therefore unsuitable for clinical applications and time-limited research projects. Consequently, we compared the effect of four different decalcification solutions applied at three different temperatures, and assessed the rate of decalcification and the implications on tissue morphology and antigenicity of mouse and rat tibiae. Bones were decalcified with 10% ethylenediaminetetraacetic acid (EDTA), 10% formic acid, 5% hydrochloric acid, and 5% nitric acid at 4C, 25C, and 37C. Decalcification in both species was fastest in nitric acid at 37C and slowest in EDTA at 4C. Histological and immunohistochemical staining confirmed that the conventional protocols of EDTA at 4C and 25C remain the best option regarding the quality of tissue preservation. Whereas formic acid at 4C is a good alternative saving about 90% of the decalcification time, hydrochloric and nitric acids should be avoided particularly in case of rat tibia. By contrast, due to their smaller size, mouse tibiae had shorter decalcification times and tolerated higher temperatures and exposure to acids much better. In conclusion, this study demonstrated that depending on the specific research question and sample size, alternative decalcification methods could be used to decrease the time of decalcification while maintaining histological accuracy.
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http://dx.doi.org/10.1369/0022155419850099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669861PMC
August 2019

Rheological Characterization of Biomaterials Directs Additive Manufacturing of Strontium-Substituted Bioactive Glass/Polycaprolactone Microfibers.

Macromol Rapid Commun 2019 Jun 1;40(11):e1900019. Epub 2019 Apr 1.

Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), 60 Musk Ave, Kelvin Grove, QLD, 4059, Australia.

Additive manufacturing via melt electrowriting (MEW) can create ordered microfiber scaffolds relevant for bone tissue engineering; however, there remain limitations in the adoption of new printing materials, especially in MEW of biomaterials. For example, while promising composite formulations of polycaprolactone with strontium-substituted bioactive glass have been processed into large or disordered fibres, from what is known, biologically-relevant concentrations (>10 wt%) have never been printed into ordered microfibers using MEW. In this study, rheological characterization is used in combination with a predictive mathematical model to optimize biomaterial formulations and MEW conditions required to extrude various PCL and PCL/SrBG biomaterials to create ordered scaffolds. Previously, MEW printing of PCL/SrBG composites with 33 wt% glass required unachievable extrusion pressures. The composite formulation is modified using an evaporable solvent to reduce viscosity 100-fold to fall within the predicted MEW pressure, temperature, and voltage tolerances, which enabled printing. This study reports the first fabrication of reproducible, ordered high-content bioactive glass microfiber scaffolds by applying predictive modeling.
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http://dx.doi.org/10.1002/marc.201900019DOI Listing
June 2019

Biofabrication of personalised anatomical models and tools for the clinic.

J Cyst Fibros 2019 03 21;18(2):161-162. Epub 2019 Feb 21.

Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia.

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http://dx.doi.org/10.1016/j.jcf.2019.02.005DOI Listing
March 2019

Smartphones for frugal three-dimensional scanning of the external ear with application to microtia.

J Plast Reconstr Aesthet Surg 2018 09 8;71(9):1362-1380. Epub 2018 Jun 8.

Institute of Health and Biomedical Innovation, Queensland University of Technology, 2 George Street, Brisbane 4000, Australia.

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http://dx.doi.org/10.1016/j.bjps.2018.05.037DOI Listing
September 2018

Melt Electrospun Bilayered Scaffolds for Tissue Integration of a Suture-Less Inflow Cannula for Rotary Blood Pumps.

Artif Organs 2018 May 13;42(5):E43-E54. Epub 2017 Dec 13.

Innovative Cardiovascular Engineering and Technology Laboratory (ICETLAB), Critical Care Research Group, The Prince Charles Hospital, Chermside, Queensland, Australia.

Implantation of left ventricular assist devices typically requires cardiopulmonary bypass support, which is associated with postoperative complications. A novel suture-less inflow cannula, which can be implanted without bypass, uses mild myocardial compression to seal the interface, however, this may lead to necrosis of the myocardium. To circumvent this issue, a bilayered scaffold has been developed to promote tissue growth at the interface between cannula and myocardium. The bilayered scaffold consists of a silicone base layer, which mimics the seal, and a melt electrospun polycaprolactone scaffold to serve as a tissue integration layer. Biocompatibility of the bilayered scaffolds was assessed by analyzing cell viability, morphology, and metabolic activity of human foreskin fibroblasts cultured on the scaffolds for up to 14 days. There was no evidence of cytotoxicity and the cells adhered readily to the bilayered scaffolds, revealing a cell morphology characteristic of fibroblasts, in contrast to the low cell adhesion observed on flat silicone sheets. The rate of cell proliferation on the bilayered scaffolds rose over the 14-day period and was significantly greater than cells seeded on the silicone sheets. This study suggests that melt electrospun bilayered scaffolds have the potential to support tissue integration of a suture-less inflow cannula for cardiovascular applications. Furthermore, the method of fabrication described here and the application of bilayered scaffolds could also have potential uses in a diverse range of biomedical applications.
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http://dx.doi.org/10.1111/aor.13018DOI Listing
May 2018

Comparison of Different Decalcification Methods Using Rat Mandibles as a Model.

J Histochem Cytochem 2017 12 29;65(12):705-722. Epub 2017 Sep 29.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.

Selection of decalcification agents is an essential consideration when processing mineralized tissues because the integrity and immunohistochemical characteristics of the tissues may be affected. Here, we report results obtained from the decalcification of rat mandibles using 10% ethylenediaminetetraacetic acid (EDTA) at room temperature (RT), 10% EDTA at 37C, 5% nitric acid, and 10% formic acid at RT. Decalcification endpoints were determined by microcomputed tomography. Morphological preservation and antigenicity were evaluated by hematoxylin and eosin staining and immunohistochemistry. Decalcification of the anterior and posterior portions of the mandible took 220 and 191 hr in 10% EDTA RT, 102 and 73 hr in 10% EDTA 37C, 13.5 and 4.3 hr in 5% nitric acid, and 140 and 36 hr in 10% formic acid, respectively. Decalcification in 10% EDTA at 37C was accelerated, but 10% EDTA at RT provided optimal results for immunohistochemistry and cellular and structural details. Decalcification using 5% nitric acid was accomplished in the shortest time and exhibited good cellular and architectural morphology, whereas 10% formic acid was suboptimal with respect to tissue and cellular morphology. Despite being the slowest method, EDTA at RT is still the recommended method for decalcifying mineralized tissues; however, if rapid decalcification is needed, 5% nitric acid is the best option, yielding acceptable tissue integrity and speed.
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http://dx.doi.org/10.1369/0022155417733708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714097PMC
December 2017

Characterization of Normal Murine Carpal Bone Development Prompts Re-Evaluation of Pathologic Osteolysis as the Cause of Human Carpal-Tarsal Osteolysis Disorders.

Am J Pathol 2017 Sep 1;187(9):1923-1934. Epub 2017 Jul 1.

Translational Research Institute, Brisbane, Queensland, Australia; University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Mater Research Institute-UQ, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. Electronic address:

Multicentric carpal-tarsal osteolysis; multicentric osteolysis, nodulosis, and arthropathy; and Winchester syndromes, skeletal dysplasias characterized by carpal/tarsal and epiphyseal abnormalities, are caused by mutations in v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B (MAFB), matrix metalloproteinase (MMP) 2, and MMP14, respectively; however, the underlying pathophysiology is unclear. Osteoclast-mediated osteolysis has been regarded as the main mechanism, but does not explain the skeletal distribution. We hypothesized that MAFB, MMP-2, and MMP-14 have integral roles in carpal/tarsal and epiphyseal bone development. Normal neonatal mouse forepaws were imaged by micro-computed tomography and examined histologically. Murine forepaw ossification occurred sequentially. Subarticular regions of endochondral ossification showed morphologic and calcification patterns that were distinct from archetypical physeal endochondral ossification. This suggests that two different forms of endochondral ossification occur. The skeletal sites showing the greatest abnormality in the carpal-tarsal osteolysis syndromes are regions of subarticular ossification. Thus, abnormal bone formation in areas of subarticular ossification may explain the site-specific distribution of the carpal-tarsal osteolysis phenotype. MafB, Mmp-2, and Mmp-14 were expressed widely, and tartrate-resistant acid phosphatase staining notably was absent in the subarticular regions of the cartilage anlagen and entheses at a time point most relevant to the human osteolysis syndromes. Thus, abnormal peri-articular skeletal development and modeling, rather than excessive bone resorption, may be the underlying pathophysiology of these skeletal syndromes.
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http://dx.doi.org/10.1016/j.ajpath.2017.05.007DOI Listing
September 2017

Effects of Topical Icing on Inflammation, Angiogenesis, Revascularization, and Myofiber Regeneration in Skeletal Muscle Following Contusion Injury.

Front Physiol 2017 7;8:93. Epub 2017 Mar 7.

Tissue Repair and Regeneration Group, Institute of Health and Biomedical Innovation, Queensland University of TechnologyBrisbane, QLD, Australia; School of Biomedical Sciences, Queensland University of TechnologyBrisbane, QLD, Australia.

Contusion injuries in skeletal muscle commonly occur in contact sport and vehicular and industrial workplace accidents. Icing has traditionally been used to treat such injuries under the premise that it alleviates pain, reduces tissue metabolism, and modifies vascular responses to decrease swelling. Previous research has examined the effects of icing on inflammation and microcirculatory dynamics following muscle injury. However, whether icing influences angiogenesis, collateral vessel growth, or myofiber regeneration remains unknown. We compared the effects of icing vs. a sham treatment on the presence of neutrophils and macrophages; expression of CD34, von Willebrands factor (vWF), vascular endothelial growth factor (VEGF), and nestin; vessel volume; capillary density; and myofiber regeneration in skeletal after muscle contusion injury in rats. Muscle tissue was collected 1, 3, 7, and 28 d after injury. Compared with uninjured rats, muscles in rats that sustained the contusion injury exhibited major necrosis, inflammation, and increased expression of CD34, vWF, VEGF, and nestin. Compared with the sham treatment, icing attenuated and/or delayed neutrophil and macrophage infiltration; the expression of vWF, VEGF, and nestin; and the change in vessel volume within muscle in the first 7 d after injury ( < 0.05). By contrast, icing did not influence capillary density in muscle 28 d after injury ( = 0.59). The percentage of immature myofibers relative to the total number of fibers was greater in the icing group than in the sham group 28 d after injury ( = 0.026), but myofiber cross-sectional area did not differ between groups after 7 d ( = 0.35) and 28 d ( = 0.30). In conclusion, although icing disrupted inflammation and some aspects of angiogenesis/revascularization, these effects did not result in substantial differences in capillary density or muscle growth.
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http://dx.doi.org/10.3389/fphys.2017.00093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339266PMC
March 2017

Numerical prediction of thrombus risk in an anatomically dilated left ventricle: the effect of inflow cannula designs.

Biomed Eng Online 2016 Dec 28;15(Suppl 2):136. Epub 2016 Dec 28.

Innovative Cardiovascular Engineering and Technology Laboratory (ICETLAB), Critical Care Research Group, The Prince Charles Hospital, Chermside, QLD, 4032, Australia.

Background: Implantation of a rotary blood pump (RBP) can cause non-physiological flow fields in the left ventricle (LV) which may trigger thrombosis. Different inflow cannula geometry can affect LV flow fields. The aim of this study was to determine the effect of inflow cannula geometry on intraventricular flow under full LV support in a patient specific model.

Methods: Computed tomography angiography imaging of the LV was performed on a RBP candidate to develop a patient-specific model. Five inflow cannulae were evaluated, which were modelled on those used clinically or under development. The inflow cannulae are described as a crown like tip, thin walled tubular tip, large filleted tip, trumpet like tip and an inferiorly flared cannula. Placement of the inflow cannula was at the LV apex with the central axis intersecting the centre of the mitral valve. Full support was simulated by prescribing 5 l/min across the mitral valve. Thrombus risk was evaluated by identifying regions of stagnation. Rate of LV washout was assessed using a volume of fluid model. Relative haemolysis index and blood residence time was calculated using an Eulerian approach.

Results: The inferiorly flared inflow cannula had the lowest thrombus risk due to low stagnation volumes. All cannulae had similar rates of LV washout and blood residence time. The crown like tip and thin walled tubular tip resulted in relatively higher blood damage indices within the LV.

Conclusion: Changes in intraventricular flow due to variances in cannula geometry resulted in different stagnation volumes. Cannula geometry does not appreciably affect LV washout rates and blood residence time. The patient specific, full support computational fluid dynamic model provided a repeatable platform to investigate the effects of inflow cannula geometry on intraventricular flow.
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http://dx.doi.org/10.1186/s12938-016-0262-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260141PMC
December 2016