Engineering the Human Osteocyte Lacunocanalicular Network In Vitro

Synopsis

We are seeking a full-time, highly motivated PhD candidate to perform cutting-edge research in bone tissue engineering at the Queensland University of Technology in the School of Biomedical Sciences.

This project will be part of the newly funded Max Planck Queensland Centre (MPQC) for the Materials Science of Extracellular Matrices, a joint initiative of the Max Planck Society for the Advancement of Science, between the Max Planck Institute of Colloids and Interfaces (MPICI) and the Queensland University of Technology (QUT) (https://www.qut.edu.au/news?id=179968).

During the course of this PhD, the candidate will drive a highly interdisciplinary project in the field of bone tissue engineering, materials science and mechanobiology, ultimately addressing a significant gap in bone research. Travel to national/international conferences and to the Max Planck Institute of Colloids and Interfaces in Germany will be available.

The successful candidate will be working under the direct supervision of Dr Nathalie Bock, Principal Investigator and Group Leader of the Bone & Tumour Bioengineering group at QUT, and under the associate supervision of Dr Flavia Medeiros Savi, an expert in bone tissue characterisation techniques and Distinguished Professor Dietmar W Hutmacher, an international leader and visionary scientist in Tissue Engineering and Biomanufacturing.

Project Background

The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized, yet the full picture of mechanisms of action has eluded scientists until recently. All hierarchical levels in bone, in both composition and multiscale architecture are known to contribute to both its mechanical and biological behaviour. Yet, the mechanisms by which the osteocyte lacunocanalicular network (LCN) regulate the bone microenvironment, and vice versa, remain vastly unknown. The consequences are the inability to truly understand how the bone organ functions, resulting in the inability to understand bone-related diseases, such as osteoarthritis, osteoporosis and osteotropic cancers.

Engineering extracellular matrix microenvironments which recapitulate the osteocyte niche is key in developing physiologically-relevant in vitro models of the osteocyte LCN, aimed at elucidating fundamental mechanisms of action. Recently, the development of biomimetic scaffolds and hydrogels has facilitated the mimicry of key aspects of various tissue microenvironments. Yet, the in vitro tissue engineering of a functional LCN in a biomimetically-relevant microenvironment has not been achieved to date, due to not knowing the multiscale microenvironmental cues that enable spontaneous osteocytogenesis from primary human cells. Therefore, the recapitulation of the human osteocyte LCN in a biomimetically-relevant tissue model represents an exciting area of research to unravel fundamental processes regulating the second largest organ of the body, bone.

The overall aim of this PhD project is to develop a multiscale biomimetic model platform of the human osteocyte LCN, using additive biomanufacturing and mechanical stimulation, that will fundamentally reshape our understanding of osteocyte biology and the nature of its interactions with the microenvironment.

Hypothesis

Multiscale biomimetic composite materials provide a physiologically-relevant model platform to recapitulate the lacunocanalicular 3D network of human osteocytes for the study of human osteocytogenesis, osteocyte mechanotransduction and transport properties.

 Aim 1 - Fabrication of multiscale fibre-reinforced hydrogel composites and effects of microenvironmental factors on osteocytogenesis, osteocyte mechanotransduction and transport properties

Matrix architecture, topography, composition and mechanical properties are the key interdependent factors involved in osteocytogenesis that will be studied in this first activity, using the principles of fibre reinforcement of hydrogels for mechanically- and chemically-enhanced biocomposites

Aim 2 - Study the effects of mechanical stimulation (physical strain and fluid flow) on the 3D osteocyte network composites using a bi-axial loading bioreactor system or microfluidic systems

Since osteocytes are the professional mechanosensing cells of bone, we will use mechanical stimulation to assess the capacity of the biomimetic composites produced in Aim 1 to sense mechanical stimuli and react to them. We will study how this compares with the native tissue, how this affect the osteocyte LCN and osteocyte phenotype, transport properties and subsequent mineralisation.

Skills and Experience

Eligible candidates considered should be:

•           Passionate about biomedical research

•           Self-motivated, able to plan and prioritise work to meet deadlines

•           Able to take initiative and undertake complex problem-solving activities

•           Able to work in a multidisciplinary team environment

•           Interested in learning and utilising a large range of laboratory-based techniques merging dissimilar fields (bone tissue engineering, additive biomanufacturing, melt electrospinnig, hydrogel manufacture, mechanical testing, materials characterization, mechanobiology)

•           Excellent in verbal and written communication skills

 Eligibility details

Australian and international applicants are eligible to apply. International students must meet all entry requirements for QUT listed here https://www.qut.edu.au/research/study-with-us/how-to-apply#Step_1_Entry_requirements

Other requirements

•       Master of Science (biomedical engineering, biotechnology, cell biology, materials science or similar), with a significant research component

•       Laboratory experience

•       Ability to work full-time

•       Strong track record (minimum of one research publication in a scientific peer-reviewed journal)

What you receive

•       A QUT Stipend Scholarship, tax exempt and indexed annually, $28,852 per annum for a period of 3 years will be provided to the successful applicant, with the possibility of a $3,000 per annum top-up scholarship for outstanding students. You will also receive a $3,000 student allocation to travel to conferences.

•       For international students, you will also receive a QUT Tuition Fee Waiver Scholarship.

•       The opportunity to work in a REAL WORLD University (https://www.qut.edu.au/), named ‘Top Young University in Australia’ (https://www.qut.edu.au/news?id=165228)

•       The opportunity to be part of the newly funded Max Planck Queensland Centre for the Materials Science of Extracellular Matrices (MPQC), under the leadership of renowned Professor Peter Fratzl and D/Prof Dietmar Hutmacher.

How to apply

Submit your application to n.bock@qut.edu.au with the following subject: ‘PhD-MPQC7NATP-2022 – Your Surname’.

Your application must include:

•                    A cover letter by the applicant (maximum 2 pages)

•                    An up-to-date CV indicating previous lab experience and skills

•                    Full academic transcript

•                    Details of three referees

An interview will be organized should you be shortlisted.