A Novel Soft Robotics Petri Dish for Tissue Engineering
Lead Research Organisation:
University of Leeds
Department Name: Mechanical Engineering
Abstract
The complexity of the physiological environment is not replicated in petri dishes or microplates. All cells are exquisitely sensitive to their micro-environment which is rich with cues from other cells, and from mechanical stimuli due to fluid flow, perfusion and movement. This is a major limitation to experiments investigating cellular responses in-vitro since the complex interplay of mechanical and biochemical factors are absent. With the use of our newly designed "soft" petri dish, we shall investigate the effect of mechanical force to cell behaviour using two cellular models, tendon cells and neurons.
Deterioration of musculoskeletal tissue to a stage where surgical intervention is needed is one of the biggest social and economic burdens (which is set to increase with an aging population) facing our healthcare system. Injuries to connective tissues at the joint can cause severe pain, reduction in mobility or decreased efficiency of limb function. Methods to culture replacement tissue are being developed due to the poor success rates of surgical repairs. However, currently these techniques are either failing to provide stimuli that mimic the real mechanical
environment of cells, or doing so in impractical costly manner.
In this project an alternative soft robotic solution will be created to supply in-vitro cell cultures with more accurate bodily strains at a fraction of the price.
The student will design and fabricate a soft Petri dish that applies multiaxial strain to the tissue on its surface. This is then incubated to provide the correct conditions for growth. Additional considerations must also be made about the functionality and safety of materials chosen. Variations in mechanical properties will cause differences in deformation during actuation and, as this is a medical device, the materials and coatings must comply with ISO 10993-1 (USFDA, 2016) to assure risks within their application are minimised. The mechanism chosen to adhere the scaffold to the Petri dish surface must also account for these details.
The student will learn how to culture primary cells on soft material. Successful culture will be subjected to various degrees of stretching to investigate the effect of stretching to cell damage.
The aim of this project is to design, fabricate and validate a soft robotic Petri dish that provides multidimensional strain to cell cultures, thus mimicking biological movement
This project will generate scientific advances in knowledge and methods for the design, fabrication of bioreactors. This technology will create a new paradigm in tissue engineering by providing 3D mechanical stimuli to cells during culture that mimic the real mechanical environment of growth in biological systems. IP generated through the project and exploitation of this will be managed through the University's Research and Innovation Service who work closely with IP Group, a UK leading venture capital partner, to support commercial exploitation routes.
Deterioration of musculoskeletal tissue to a stage where surgical intervention is needed is one of the biggest social and economic burdens (which is set to increase with an aging population) facing our healthcare system. Injuries to connective tissues at the joint can cause severe pain, reduction in mobility or decreased efficiency of limb function. Methods to culture replacement tissue are being developed due to the poor success rates of surgical repairs. However, currently these techniques are either failing to provide stimuli that mimic the real mechanical
environment of cells, or doing so in impractical costly manner.
In this project an alternative soft robotic solution will be created to supply in-vitro cell cultures with more accurate bodily strains at a fraction of the price.
The student will design and fabricate a soft Petri dish that applies multiaxial strain to the tissue on its surface. This is then incubated to provide the correct conditions for growth. Additional considerations must also be made about the functionality and safety of materials chosen. Variations in mechanical properties will cause differences in deformation during actuation and, as this is a medical device, the materials and coatings must comply with ISO 10993-1 (USFDA, 2016) to assure risks within their application are minimised. The mechanism chosen to adhere the scaffold to the Petri dish surface must also account for these details.
The student will learn how to culture primary cells on soft material. Successful culture will be subjected to various degrees of stretching to investigate the effect of stretching to cell damage.
The aim of this project is to design, fabricate and validate a soft robotic Petri dish that provides multidimensional strain to cell cultures, thus mimicking biological movement
This project will generate scientific advances in knowledge and methods for the design, fabrication of bioreactors. This technology will create a new paradigm in tissue engineering by providing 3D mechanical stimuli to cells during culture that mimic the real mechanical environment of growth in biological systems. IP generated through the project and exploitation of this will be managed through the University's Research and Innovation Service who work closely with IP Group, a UK leading venture capital partner, to support commercial exploitation routes.
Planned Impact
Regenerative Medicine been defined as "an interdisciplinary approach, spanning tissue
engineering, stem cell biology, gene therapy, cellular therapeutics, biomaterials (scaffolds and matrices),nanoscience, bioengineering and chemical biology that seeks to repair or replace damaged or diseased human cells or tissues to restore normal function, (UK Strategy for Regenerative Medicine). CDT TERM will focus on acellular therapies, scaffolds,autologous cells and regenerative devices, which can be delivered to patients as class three device interventions, thus reducing the time and cost of translation and which provide an opportunity to deliver economic growth and benefits to health in the next decade. The primary beneficiaries of CDT TERM are patients, the health service, UK industry, as well as the academic community and the students themselves. Recognising that the impact and benefit from CDT TERM will arise in the future, the statements describing impact below are supported by evidence of actual impact from our existing research and training.
Patients will benefit from regenerative interventions, which address unmet clinical needs, have improved safety and reliability, have been stratified to meet patients needs and manufactured in a cost effective manner. An example of impact arising from previous students work is a new acellular scaffold for young adult heart valve repair, which has demonstrated improved clinical outcomes at five years.
The Health Service will benefit from collaborations on research, development and evaluation of technologies, through existing partnerships with National Health Service Blood and Transplant NHSBT and the Leeds Biomedical Musculoskeletal Research Unit LMBRU. NHSBT will benefit through collaborative projects, through technology transfer, through enhancement of manufacturing processes, through pre-clinical evaluation of products and supply of trained personnel. We currently collaborate on heart valves, skin, ligaments and arteries, have licensed patents on acellular bioprocesses, and support product and process developments with pre-clinical testing and simulation. LMBRU and NHS clinicians will benefits from our collaborative research and training environment and access to our research expertise, facilities and students. Existing collaborative projects include, delivery devices for minimally manipulated stem cells and applied imaging for early OA.
Industry will benefit from supply of highly trained multidisciplinary engineers and scientists, from collaborative research and development projects, from creation and translation of IP, creation of spinout companies and through access to unique equipment, facilities and expertise. We have demonstrated: successful spin outs in form of Tissue Regenix and Credentis; successful commercialisation of a novel biological scaffolds for vascular patch repair; sustainable long term R and D and successful licensing of technology with DePuy; collaborative research with Invibio, partnering with Simulation Solutions to develop new pre-clinical simulation systems, which been adopted by regulatory agencies such as China FDA. Our graduates and researchers are employed by our industry partners.
The academic community will benefit through collaborative research and access to our facilities. We have funded collaborations with over 30 academic institutions in UK and internationally. The CDT TERM will support these collaborations and the academic partners will support student research and training. The CDT students will benefit from enhanced integrated multidisciplinary training and research, a cohort experience focused on research innovation and translation, access to our research partners, industry and clinicians. Feedback from existing students has identified the benefit of the multidisciplinary experience, the depth and breadth of excellence in our research base, the outstanding facilities and the added value of the cohort training.
engineering, stem cell biology, gene therapy, cellular therapeutics, biomaterials (scaffolds and matrices),nanoscience, bioengineering and chemical biology that seeks to repair or replace damaged or diseased human cells or tissues to restore normal function, (UK Strategy for Regenerative Medicine). CDT TERM will focus on acellular therapies, scaffolds,autologous cells and regenerative devices, which can be delivered to patients as class three device interventions, thus reducing the time and cost of translation and which provide an opportunity to deliver economic growth and benefits to health in the next decade. The primary beneficiaries of CDT TERM are patients, the health service, UK industry, as well as the academic community and the students themselves. Recognising that the impact and benefit from CDT TERM will arise in the future, the statements describing impact below are supported by evidence of actual impact from our existing research and training.
Patients will benefit from regenerative interventions, which address unmet clinical needs, have improved safety and reliability, have been stratified to meet patients needs and manufactured in a cost effective manner. An example of impact arising from previous students work is a new acellular scaffold for young adult heart valve repair, which has demonstrated improved clinical outcomes at five years.
The Health Service will benefit from collaborations on research, development and evaluation of technologies, through existing partnerships with National Health Service Blood and Transplant NHSBT and the Leeds Biomedical Musculoskeletal Research Unit LMBRU. NHSBT will benefit through collaborative projects, through technology transfer, through enhancement of manufacturing processes, through pre-clinical evaluation of products and supply of trained personnel. We currently collaborate on heart valves, skin, ligaments and arteries, have licensed patents on acellular bioprocesses, and support product and process developments with pre-clinical testing and simulation. LMBRU and NHS clinicians will benefits from our collaborative research and training environment and access to our research expertise, facilities and students. Existing collaborative projects include, delivery devices for minimally manipulated stem cells and applied imaging for early OA.
Industry will benefit from supply of highly trained multidisciplinary engineers and scientists, from collaborative research and development projects, from creation and translation of IP, creation of spinout companies and through access to unique equipment, facilities and expertise. We have demonstrated: successful spin outs in form of Tissue Regenix and Credentis; successful commercialisation of a novel biological scaffolds for vascular patch repair; sustainable long term R and D and successful licensing of technology with DePuy; collaborative research with Invibio, partnering with Simulation Solutions to develop new pre-clinical simulation systems, which been adopted by regulatory agencies such as China FDA. Our graduates and researchers are employed by our industry partners.
The academic community will benefit through collaborative research and access to our facilities. We have funded collaborations with over 30 academic institutions in UK and internationally. The CDT TERM will support these collaborations and the academic partners will support student research and training. The CDT students will benefit from enhanced integrated multidisciplinary training and research, a cohort experience focused on research innovation and translation, access to our research partners, industry and clinicians. Feedback from existing students has identified the benefit of the multidisciplinary experience, the depth and breadth of excellence in our research base, the outstanding facilities and the added value of the cohort training.
