Biofabrication for Personalised Vascular Surgery Prognosis, Training, and Treatment 

Advanced Queensland Industry Research Fellowship (2019-2022)

  • Development of a numerical and experimental model to optimise graft anastomosis in peripheral arteries (Sabrina Schoenborn - UQ)

The primary cause of mid-term occlusive graft failure in small-diameter vascular bypass grafts is the development of intimal hyperplasia. Major causes of intimal hyperplasia have been identified as the tubular compliance mismatch between artery and graft and the anastomotic compliance mismatch between artery and anastomosis device, such as a stiff suture, which attaches the graft to the artery. With advanced vascular grafts offering physiological tubular compliance and biodegradable vascular grafts showing promising results in animal models and clinical trials, the development of compliant biodegradable anastomosis solutions has become an emerging clinical issue. To address this unmet need, a numerical fluid-structure interaction simulation platform is being developed in this project to aid in the design and testing of artery-graft anastomosis strategies and to allow the study of fluid flow and mechanical behaviour around anastomosis sites. Experimental validation is facilitated via compliant silicone arterial phantoms with matched compliance which are manufactured using additive manufacturing technology.

  • A diagnostic software suite using machine learning to predict intracranial aneurysm rupture (Mitchell Johnson - UQ)

Intracranial aneurysms are bulging, weak outpouchings of arteries that supply blood to the brain. They are relatively common, and in rare cases, burst and become subarachnoid haemorrhages with catastrophic 35% mortality and 35% lifelong morbidity rates. While surgical treatments are available to decrease  aneurysm rupture risk, aneurysms are rarely detected prior to rupture and there remains little guidance over which aneurysms are prone to future rupture. Leveraging medical image analysis and data science, this project seeks to develop computational algorithms which can automatically identify aneurysms from brain images and develop fundamental understanding around aneurysm imaging factors which are indicative of rupture risk, such as shape, location, and more. An ultimate goal of this research program is to develop an automated radiology software that can serve as a second set of eyes for the untrained radiologist, rapidly searching through the many unrelated brain images in a healthcare service to screen for aneurysms and, if an aneurysm is identified, predict whether the aneurysm is particularly at-risk of rupture. 

  • Soft robotic devices for emulating vascular mechanobiology (Cody Fell - QUT)

Tissue biomanufacturing aims to produce laboratory-grown stem cell grafts, complex organoid systems, and engineered organs-on-a-chip for clinical therapies and pharmaceutical models. However, biomanufacturing systems remain expensive, inconsistent, and limited in their recapitulation of native tissue mechanics. Soft robotics are ideal platforms for emulating physiologically complex mechanical stimuli to enhance patient-specific tissue maturation. The kneecap’s femoropopliteal artery (FPA) represents a highly flexible tissue across multiple axes during blood flow, walking, standing, and crouching, and these complex biomechanics are implicated in the FPA’s frequent presentation of peripheral artery disease. To investigate how patient-specific FPA mechanics effect lab-grown arterial tissue, we developed a bio-hybrid soft robot (BSR) bioreactor to recapitulate patient-, disease-, and lifestyle-specific mechanobiology for disease understanding, treatment simulations, and for lab-grown tissue grafts.

  • Combining additive manufacturing and soft robotics for improved biomimetic tissue engineered constructs (Brenna Devlin - QUT)

Movement is critical to healthy tissue development. The mechanical forces apparent during a heartbeat, during breathing, and during everyday exercise regulate the performance of individual cells, such as muscle and bone cells, and their interactions within their local tissue microenvironment. Current cell culture platforms fail to recapitulate these mechanical forces, which are necessary to faithfully recreate healthy or diseased tissue in the laboratory. We propose a soft robotic bioreactor able to plug-in 3D cell culture cartridges and impart physiological mechanical loading conditions. We have demonstrated the capabilities of our bioreactor in mimicking flexible arterial tissue in 2D, which we redesign to incorporate melt electrowritten 3D scaffolds. The bioreactor’s multi-axial mechanical biomimicry is a first of its kind, offering tailored tissue morphology and differentiation, well-suited for future musculoskeletal, osteochondral, or dermal tissue regeneration or drug testing.

  • 3D-printed composite biomaterials for personalised vascular implants (Trent Brooks-Richards - QUT)

Bioresorbable vascular stents (BVS) are a highly anticipated transition from metallic stents, potentially reducing common latent complications while allowing restoration of vasomotion. Initial clinical trials of BVS indicate a need for materials with improved mechanical and degradation characteristics. Here, we show a preliminary investigation using graphene oxide (GO) to mechanically reinforce medical-grade poly(ɛ-caprolactone) (PCL) fabricated using fused deposition modelling and melt electrowriting (MEW) toward use in patient-specific bioresorbable stent technology. We evaluate nanocomposite printing ink quality and rheology. Once printed into cylindrical scaffolds of different scales and geometries, we evaluate the improved multi-axial mechanics of the composite ink and endothelial cell regeneration kinetics. Additive manufacturing techniques combined with resorbable, reinforced composite biomaterials such as GO-PCL hold promise as patient-specific stenting solutions to arterial lesions for improved patient outcomes with reduced latent complications.

 

Engineering Tissue Organisation Using Intelligent Additive Biomanufacturing

Australian Research Council DECRA Fellowship (2022-2025)

Replacing wounds with surgical grafts remains challenging as an insufficient mass transfer of nutrients and metabolites can lead to tissue necrosis. Blood vessels must rapidly incorporate throughout tissue grafts for survival, but this is difficult for large grafts or for impaired (diabetic) host tissue. The intra-operative placement of vessel conduits within or around grafts has improved tissue revascularisation and regeneration. However, adding vessels to grafts requires additional morbidity sites and their angiogenic effect remains inconsistent. The project aims to manufacture lab-grown patient-specific grafts with inbuilt vascular conduits optimally designed for defect-specific regeneration and patterned tissue maturation with minimal patient morbidity. These conduit-grafts will be manufactured and validated in bioreactor tissue culture, with an aim toward future animal trials.

Surgical treatments of cerebrovascular conditions, such as intracranial aneurysms, are difficult to optimise for patient-specific conditions due to the variety of presentations and low margin for error. The ability to trial different medical, endovascular or surgical approaches on patient-specific presentations prior to open craniotomy could develop better therapies, but no models recapitulate cerebrovascular: (1) anatomy (2) mechanics and (3) biology simultaneously, all of which influence long-term treatment success rates. These cerebrovascular models would help solve fundamental questions of whether to operate, when to operate, and how to operate. This project will develop a manufacturing framework to generate a soft material macro/microfluidic cerebrovascular mimicry from patient images which in its first design is able to incorporate endothelial cells and medium perfusion to simulate physiological mechanobiology. Cerebrovascular surgery (stent, coil implants) will be simulated in the brain model, which aims to act as a preoperative testbed to compare surgical approaches and engineer better implant designs.

  • Engineering tissue organisation under 3D printed microconfinement and bioreactor mass transport (PhD scholarships avaliable soon)

PhD scholarships related to a ARC DECRA grant aiming to organize and shape the formation of lab-grown tissue by 3D printing structures which control the behaviour of cells. This cell behaviour control will be accomplished through an interdisciplinary and multiscale pipeline of additive micromanufacturing, bioreactor engineering, cell culture, single-cell imaging, and computational modelling. In contrast with current empirical approaches, this quantitative and predictive understanding of how to control biological processes within 3D printed environments will design and engineer more robust, customisable, scalable, and economical cell culture platforms able to optimally manufacture bespoke and complex 3D tissues for future biomedical products. In collaboration with Prof Maria Woodruff (QUT).