The impact of angiogenesis for tissue engineering application
Lead Research Organisation:
University of Leeds
Department Name: Mechanical Engineering
Abstract
There is a major clinical need to repair and/or regenerate living tissue substitutes .Current approaches, such as autogenous tissue grafts, allogenic tissue grafts and organ transplantation have many limitations, all of which are far from attaining an ideal clinical outcome.
Tissue engineering is an established yet fast-growing area, which offers new and possibly step changing solutions for clinical practice, outcomes that will fundamentally benefit the patient. Successful advances to the field will have a huge social and economic impact worldwide.
Tissue engineering is a widely accepted branch of science and despite the investment in the area over the last two decades, the success cases in clinical translation for repairing large scale tissue loss or regenerating organ functionality, are still very limited. One of the bottlenecks for scaling up this type of tissue engineering technology in clinical applications is angiogenesis and/or vascularisation of the engineered tissues.
In this project, a multidisciplinary approach will be utilised to combine material science (Dr Robert Davies) with stem cell biology and tissue engineering expertise (Dr Yang: with clinical background).
Biocompatible hydrogels such as (but not limited to) self-assembling peptide scaffold(s) will be developed and optimised to support human mesenchymal stem/stromal cells growth. Different culture conditions (such as hypoxia, iPSCs, diffusion/perfusion culture), 3D in vitro models, MicroTissue models and in vivo models will be used for enhancing angiogenesis/vasculogenesis during the tissue engineering procedure.
If successful, the outputs from this project will provide evidence for vascularisation of tissue engineered products for scaling up large size tissue repair and/or functional organ tissue regeneration.
The aim of this project is to use novel biomaterial based scaffolds to create a biomimetic microenvironment for enhancing human mesenchymal stem/stromal cells angiogenesis and/or vasculogenesis in vitro and/or in vivo. With the explicit aim to develop a scalable tissue engineering technology ready for clinical translation.
The project shows synergy with the EPSRC's Healthcare and Technologies Theme - Developing Future Therapies. The objectives include:
A) Screening our current library of patented self-assembling peptide scaffolds and/or other hydrogel(s) for enhancing vasculogenesis and/or angiogenesis. The results of which will inform the development of novel materials (through an iterative approach)
B) The effect of hypoxia culture conditions on the vasculogenesis of MSCs in monolayer culture and 3D models.
C) Optimisation of different growth factors and/or combination, and/or other approaches (e.g. gene therapy, epigenetics and signaling pathways) for enhancing vasculogenesis/angiogenesis.
D) The effect of selected biomaterials, stem/stromal cells and culture conditions on enhancing vasculogenesis/angiogenesis in vivo.
The development/selection of suitable biomaterial scaffolds are fundamentally based upon physical science research approaches. The successful combination of scaffolds, cells and specific environmental conditions, may lead to new patent filings and provide the necessary evidence for commercialisation of the selected combination.
In addition, the development and/or optimisation of microenvironments will further the understanding in this field and will provide useful information for bioreactor design (new products).
3D cell culture models and in vitro bioreactors are bioengineering approaches, which will generate new knowledge on the development of new models and/or devices.
Tissue engineering is an established yet fast-growing area, which offers new and possibly step changing solutions for clinical practice, outcomes that will fundamentally benefit the patient. Successful advances to the field will have a huge social and economic impact worldwide.
Tissue engineering is a widely accepted branch of science and despite the investment in the area over the last two decades, the success cases in clinical translation for repairing large scale tissue loss or regenerating organ functionality, are still very limited. One of the bottlenecks for scaling up this type of tissue engineering technology in clinical applications is angiogenesis and/or vascularisation of the engineered tissues.
In this project, a multidisciplinary approach will be utilised to combine material science (Dr Robert Davies) with stem cell biology and tissue engineering expertise (Dr Yang: with clinical background).
Biocompatible hydrogels such as (but not limited to) self-assembling peptide scaffold(s) will be developed and optimised to support human mesenchymal stem/stromal cells growth. Different culture conditions (such as hypoxia, iPSCs, diffusion/perfusion culture), 3D in vitro models, MicroTissue models and in vivo models will be used for enhancing angiogenesis/vasculogenesis during the tissue engineering procedure.
If successful, the outputs from this project will provide evidence for vascularisation of tissue engineered products for scaling up large size tissue repair and/or functional organ tissue regeneration.
The aim of this project is to use novel biomaterial based scaffolds to create a biomimetic microenvironment for enhancing human mesenchymal stem/stromal cells angiogenesis and/or vasculogenesis in vitro and/or in vivo. With the explicit aim to develop a scalable tissue engineering technology ready for clinical translation.
The project shows synergy with the EPSRC's Healthcare and Technologies Theme - Developing Future Therapies. The objectives include:
A) Screening our current library of patented self-assembling peptide scaffolds and/or other hydrogel(s) for enhancing vasculogenesis and/or angiogenesis. The results of which will inform the development of novel materials (through an iterative approach)
B) The effect of hypoxia culture conditions on the vasculogenesis of MSCs in monolayer culture and 3D models.
C) Optimisation of different growth factors and/or combination, and/or other approaches (e.g. gene therapy, epigenetics and signaling pathways) for enhancing vasculogenesis/angiogenesis.
D) The effect of selected biomaterials, stem/stromal cells and culture conditions on enhancing vasculogenesis/angiogenesis in vivo.
The development/selection of suitable biomaterial scaffolds are fundamentally based upon physical science research approaches. The successful combination of scaffolds, cells and specific environmental conditions, may lead to new patent filings and provide the necessary evidence for commercialisation of the selected combination.
In addition, the development and/or optimisation of microenvironments will further the understanding in this field and will provide useful information for bioreactor design (new products).
3D cell culture models and in vitro bioreactors are bioengineering approaches, which will generate new knowledge on the development of new models and/or devices.
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.
Organisations
People |
ORCID iD |
| Xuebin Yang (Primary Supervisor) | |
| Philip Booth (Student) |