Periodic Reporting for period 2 - TRiAnkle (3D BIOPRINTED PERSONALISED SCAFFOLDS FOR TISSUE REGENERATION OF ANKLE JOINT)
Periodo di rendicontazione: 2022-07-01 al 2023-12-31
Tendinopathies and osteoarthritis (OA) are extremely common and these injuries associate with high health and socioeconomic costs, long-term postoperative rehabilitation, and loss of productivity. To date, none of the existing surgical or non-surgical alternatives have provided a successful long-term effect, and often the treated tissues do not restore their complete strength and functionality. To fill the critical gap of proper treatments TRiAnkle proposes to develop 3D bioprinted scaffolds based on collagen and gelatine, functionalised with stem cells and/or nanoencapsulated regenerative factors.
The surgical implantation of these new functionalised biomaterials will enable the targeted delivery of the mentioned biologically active agents to promote cell growth and differentiation to enable better and faster regeneration of injured collagen-rich tissues like articular cartilage, ligament, and tendon of the ankle.
Two case-studies will be implemented: the partial rupture (>50%) of Achilles tendon and osteochondral cartilage injuries, which will serve as a technological platform to deliver new regenerative therapies for any other articular, tendinous, or ligament diseases of weight-bearing joints.
By achieving this goal, TRiAnkle will enable, in comparison with current surgical treatments: - To increase by 10-15% of the ankle joints functionality recovery ratios due to the presence of pro-regenerative components that promote the healing process decreasing also the risk of re-rupture or recidivation. - To reduce the recovery time and the associated healthcare costs up to 50% due to the use of scaffolds that mimic the natural structure and mechanical properties of joint tissues.
TRiAnkle will be implemented by a multidisciplinary team made up of biomaterial production companies, manufacturing technologies experts, material engineers, preclinical validation centers, healthcare professionals, patients associations, and experts in ethical, regulatory, and exploitation.
The surgical implantation of these new functionalised biomaterials will enable the targeted delivery of the mentioned biologically active agents to promote cell growth and differentiation to enable better and faster regeneration of injured collagen-rich tissues like articular cartilage, ligament, and tendon of the ankle.
Two case-studies will be implemented: the partial rupture (>50%) of Achilles tendon and osteochondral cartilage injuries, which will serve as a technological platform to deliver new regenerative therapies for any other articular, tendinous, or ligament diseases of weight-bearing joints.
By achieving this goal, TRiAnkle will enable, in comparison with current surgical treatments: - To increase by 10-15% of the ankle joints functionality recovery ratios due to the presence of pro-regenerative components that promote the healing process decreasing also the risk of re-rupture or recidivation. - To reduce the recovery time and the associated healthcare costs up to 50% due to the use of scaffolds that mimic the natural structure and mechanical properties of joint tissues.
TRiAnkle will be implemented by a multidisciplinary team made up of biomaterial production companies, manufacturing technologies experts, material engineers, preclinical validation centers, healthcare professionals, patients associations, and experts in ethical, regulatory, and exploitation.
The project has just been launched in January 2021. The proposed work plan for the TRiAnkle project has been carefully designed to achieve the planned objectives. The project has been divided into 8 Work Packages (WPs), which have been structured in three different groups:
The first group (WP1, WP2 and WP3) will be devoted to the development of the TRiAnkle therapeutic products and to its in vitro and in vivo validation. In parallel to the biomaterial development, stem cells will be produced, tools for cell differentiation and scaffold functionalization will be developed (WP1 and WP2). Moreover, bioreactors will be used for long-term mechanobiological in vitro studies and pre-clinical assays will be developed for the in vivo validation of the cell-laden scaffolds (WP3).
The second group of WPs (WP4 and WP5) are dedicated to ethical, regulatory and social aspects of the products and technologies developed. WP4 will deal with the regulatory aspects of the products to facilitate later clinical transfer of the successful approaches as well as the ethical components related to the use of human cells, animal experiments and engagement of patients and doctors. WP5 will work on patient engagement and social impact by organising activities with potential stakeholders (especially patients) and work on the healthcare economics related to the successful therapies to support a future clinical development plan that can generate valid data for Health Technology Assessments (HTA).
Finally, WP6 will develop the business plan, the exploitation strategy and the IPR management of the new therapy. WP7 involves dissemination and communication activities while WP8 deals with scientific coordination and project management.
The first group (WP1, WP2 and WP3) will be devoted to the development of the TRiAnkle therapeutic products and to its in vitro and in vivo validation. In parallel to the biomaterial development, stem cells will be produced, tools for cell differentiation and scaffold functionalization will be developed (WP1 and WP2). Moreover, bioreactors will be used for long-term mechanobiological in vitro studies and pre-clinical assays will be developed for the in vivo validation of the cell-laden scaffolds (WP3).
The second group of WPs (WP4 and WP5) are dedicated to ethical, regulatory and social aspects of the products and technologies developed. WP4 will deal with the regulatory aspects of the products to facilitate later clinical transfer of the successful approaches as well as the ethical components related to the use of human cells, animal experiments and engagement of patients and doctors. WP5 will work on patient engagement and social impact by organising activities with potential stakeholders (especially patients) and work on the healthcare economics related to the successful therapies to support a future clinical development plan that can generate valid data for Health Technology Assessments (HTA).
Finally, WP6 will develop the business plan, the exploitation strategy and the IPR management of the new therapy. WP7 involves dissemination and communication activities while WP8 deals with scientific coordination and project management.
The TRiAnkle proposal is ambitious as it requires the successful synergy of different scientific expertise and backgrounds such as biomaterials engineering, additive manufacturing, rapid and custom-made prototyping, regenerative medicine, cell therapy, tissue-specific cell delivery and transplantation, advanced clinical imaging, CAD/CAM medical software, 3D-bioprinting, nanotechnology, appropriate large in vivo models imitating human pathologies and specialized orthopaedic surgery. Altogether, TRiAnkle will represent a significant step forward in the development of personalized, tissue-specific functionalised biomimetic scaffolds suitable for the targeted cell delivery and osteoarticular tissue regeneration of the different weight-bearing joint structures (cartilage, tendon, and ligament).
TRiAnkle therapies will contribute to reducing the direct costs for OA treatment by 16% resulting in €12.24 billion annual savings for the EU health system. TRiAnkle will also reduce tendinopathies therapies-related costs by 20% causing €28 billion savings for health systems worldwide. Moreover, the application of these advanced therapies will enable to improve social reintegration of patients with diseases of weight-bearing joints by improving the employability and work performance of people with high physical activity, such as construction workers, physiotherapists, or athletes. Fast and good recovery is of high economic and social importance for these patients.
TRiAnkle project also aims to contain societal costs by developing advanced gelatine and collagen-based therapies that improve the Quality Adjusted Life Years (QALYs) of patients suffering from ankle joint ruptures. Currently, about 30% of the patients with high physical activity, such as athletes, do not recover pre-injury performance levels after any of the current treatments. This is a major social drawback for women and men that rely on physical work and their income and social integration can be significantly compromised due to osteoarticular joint diseases. The know-how acquired through this clinical experience will be used in the project to better design the combined ATMPs to be used for treating tendon ruptures.
Beyond funding, extensive government support would drive the global regenerative medicine market as they are responsible for the regulatory development path that drives the future commercialization of biomaterials. As part of the communication plan of TRiAnkle, the consortium will define specific dissemination actions to increase the EU attractiveness for the clinical development of regenerative medicine by regional, national, and European administrations. This may help to contribute to harmonise European regulation and create a viable governance pathway for regenerative medicines. Moreover, the governments are aware of the financial advantages of investing in regenerative medicine instead of financing palliative treatments, especially with an ageing population that threatens the current sustainability of the European healthcare systems.
TRiAnkle therapies will contribute to reducing the direct costs for OA treatment by 16% resulting in €12.24 billion annual savings for the EU health system. TRiAnkle will also reduce tendinopathies therapies-related costs by 20% causing €28 billion savings for health systems worldwide. Moreover, the application of these advanced therapies will enable to improve social reintegration of patients with diseases of weight-bearing joints by improving the employability and work performance of people with high physical activity, such as construction workers, physiotherapists, or athletes. Fast and good recovery is of high economic and social importance for these patients.
TRiAnkle project also aims to contain societal costs by developing advanced gelatine and collagen-based therapies that improve the Quality Adjusted Life Years (QALYs) of patients suffering from ankle joint ruptures. Currently, about 30% of the patients with high physical activity, such as athletes, do not recover pre-injury performance levels after any of the current treatments. This is a major social drawback for women and men that rely on physical work and their income and social integration can be significantly compromised due to osteoarticular joint diseases. The know-how acquired through this clinical experience will be used in the project to better design the combined ATMPs to be used for treating tendon ruptures.
Beyond funding, extensive government support would drive the global regenerative medicine market as they are responsible for the regulatory development path that drives the future commercialization of biomaterials. As part of the communication plan of TRiAnkle, the consortium will define specific dissemination actions to increase the EU attractiveness for the clinical development of regenerative medicine by regional, national, and European administrations. This may help to contribute to harmonise European regulation and create a viable governance pathway for regenerative medicines. Moreover, the governments are aware of the financial advantages of investing in regenerative medicine instead of financing palliative treatments, especially with an ageing population that threatens the current sustainability of the European healthcare systems.