Periodic Reporting for period 3 - ADMAIORA (ADvanced nanocomposite MAterIals fOr in situ treatment and ultRAsound-mediated management of osteoarthritis)
Reporting period: 2022-02-01 to 2023-12-31
GENERAL INFORMATION
ADMAIORA (ADvanced nanocomposite MAterIals fOr in situ treatment and ultRAsound-mediated management of osteoarthritis) is a research project funded under the Horizon 2020 EU Framework Programme (Call: H2020-NMBP-TR-IND-2018, Research and Innovation action), coordinated by Prof. Leonardo Ricotti at the Scuola Superiore Sant’Anna (Pisa, Italy).
WHAT IS OSTEOARTHRITIS?
Osteoarthritis (OA) is a major burden that affects ~ 40 million of EU citizens, with enormous direct and indirect costs for the European healthcare systems. This disease involves the degeneration of cartilage and other joint structures and is one of the most common causes of pain and disability in middle-aged and elderly people. Over the next decade, the number of people affected by OA is expected to double due to population ageing and increased rate of obesity (a risk factor for OA), resulting in a significant burden at the society level. According to the United Nations, by 2050, 130 million people will suffer from OA worldwide, of whom 40 million will be severely disabled by the disease. This represents an issue that is largely unsolved, at present.
THE PROJECT
ADMAIORA aims, in the long-term, at increasing the healthy and active lifespan of people affected by OA, by considerably slowing down or even stopping the degeneration process, thus delaying by several years or even avoiding surgical interventions for total joint replacement.
Overall, ADMAIORA targeted a ground-breaking paradigm that may revolutionize OA treatment. Within the project time-frame (5 years) the target was to achieve a considerable reduction of joint degeneration in OA animal models treated with the ADMAIORA technologies, with respect to control (untreated) ones. To achieve this ambitious objective the Consortium developed injectable hydrogels embedded with graphene oxide nanoflakes, conferring higher mechanical and lubrication properties, chondrogenicity and adhesion to the cartilage tissue, and piezoelectric nanoparticles enabling responsivity to remote wireless ultrasound waves, triggering chondrogenic differentiation and anti-inflammatory effects. Stromal cells derived from adipose tissue were entrapped in the hydrogels. The cell-laden nanocomposite was delivered in situ through an innovative handheld 3D bioprinter, developed in the form of an arthroscopic tool. A custom brace was designed and equipped with ultrasound probes for both monitoring the joint status and stimulating the implanted piezoelectric biomaterial. A dedicated App allowed a direct connection between patient and physician in an Internet of Things framework.
ADMAIORA (ADvanced nanocomposite MAterIals fOr in situ treatment and ultRAsound-mediated management of osteoarthritis) is a research project funded under the Horizon 2020 EU Framework Programme (Call: H2020-NMBP-TR-IND-2018, Research and Innovation action), coordinated by Prof. Leonardo Ricotti at the Scuola Superiore Sant’Anna (Pisa, Italy).
WHAT IS OSTEOARTHRITIS?
Osteoarthritis (OA) is a major burden that affects ~ 40 million of EU citizens, with enormous direct and indirect costs for the European healthcare systems. This disease involves the degeneration of cartilage and other joint structures and is one of the most common causes of pain and disability in middle-aged and elderly people. Over the next decade, the number of people affected by OA is expected to double due to population ageing and increased rate of obesity (a risk factor for OA), resulting in a significant burden at the society level. According to the United Nations, by 2050, 130 million people will suffer from OA worldwide, of whom 40 million will be severely disabled by the disease. This represents an issue that is largely unsolved, at present.
THE PROJECT
ADMAIORA aims, in the long-term, at increasing the healthy and active lifespan of people affected by OA, by considerably slowing down or even stopping the degeneration process, thus delaying by several years or even avoiding surgical interventions for total joint replacement.
Overall, ADMAIORA targeted a ground-breaking paradigm that may revolutionize OA treatment. Within the project time-frame (5 years) the target was to achieve a considerable reduction of joint degeneration in OA animal models treated with the ADMAIORA technologies, with respect to control (untreated) ones. To achieve this ambitious objective the Consortium developed injectable hydrogels embedded with graphene oxide nanoflakes, conferring higher mechanical and lubrication properties, chondrogenicity and adhesion to the cartilage tissue, and piezoelectric nanoparticles enabling responsivity to remote wireless ultrasound waves, triggering chondrogenic differentiation and anti-inflammatory effects. Stromal cells derived from adipose tissue were entrapped in the hydrogels. The cell-laden nanocomposite was delivered in situ through an innovative handheld 3D bioprinter, developed in the form of an arthroscopic tool. A custom brace was designed and equipped with ultrasound probes for both monitoring the joint status and stimulating the implanted piezoelectric biomaterial. A dedicated App allowed a direct connection between patient and physician in an Internet of Things framework.
An injectable nanocomposite hydrogel embedding adipose tissue-derived stromal cells (ASCs) has been successfully tested in vitro and in vivo. In vitro results showed a considerable boost of chondrogenesis and a reduction of inflammation in ASCs, when the nanocomposite was stimulated with controlled ultrasound waves. Tests compliant with ISO 10993 also showed an excellent safety of the hydrogel in vivo. This nanocomposite hydrogels (that has been patented at the beginning of the project) reached a preclinical maturation level (TRL = 5), as expected.
Results on the novel handheld arthroscopic device allowed filing a patent, publishing a paper on Ann. Biomed. Eng. and preparing another publication currently under review on Sci. Rep. The KPI was a usability score of at least 7 out of 10 by skilled surgeons. This objective was largely matched, with an average score of 8.6 out of 10. The technology is promising, and it is not far from having a possible commercial impact.
Results on a highly controlled ultrasound stimulation platform allowed filing a patent and publishing two papers: one on its validation, on Ultrasonics, another one on its direct use on macrophages, on APL Bioeng. All KPIs (broad range of frequencies and intensities and a dose error < 2.5%) were matched.
The efforts on a smart wearable brace for therapy delivery and monitoring, in an internet-of-things framework allowed filing a patent, publishing a paper on Sci. Rep., another paper on IEEE Transl. Eng. Health Med. and preparing another publication currently under review on IEEE Open J. Eng. Med. Biol. The KPI was a usability score of at least 7 out of 10 by patients. The average score achieved was 8.8 out of 10. A start-up company was founded based on these results. It will pursue its commercial exploitation.
Dissemination activities were rich and successful. The project website received, on average, 500 visits per month, with visitors from 72 different countries. The Consortium organized four scientific workshops/simposia and participated in several events, with a total of 69 oral or poster presentations delivered. Overall, 23 publications were achieved on ISI journals. This constitutes an impactful result in the scientific community, covering all scientific and technical aspects of the project. Furthermore, the Consortium published eight conference proceedings and 28 conference abstracts.
The project communication campaign was intense and impactful, with several initiatives that reached a large number of citizens. An interview of the project Coordinator at the SuperQuark program reached 2.263.000 people (13% share of Italian TV audience on that day). Concerning social media, 953 followers were achieved on Facebook and Twitter. The Consortium members made 7 TV/radio interviews, 19 press news and 28 internet news. Four large non-technical events were organized to communicate the project concept and results to the general public.
The project achieved excellent exploitation outcomes. The Consortium filed a large portfolio of patents (4 patents: WO2020174395A1, WO2021014331A1, WO2022074632A1, WO2023275771A1), protecting the IP generated in a thorough way. A start-up was founded (MyEcho S.r.l. https://www.myechosrl.com/) which was born grounded on results obtained during the project course concerning wearable braces. The start-up has already received two national prizes (the “Most innovative spin-off company in Tuscany award”, assigned during the “Start Cup Toscana” event on 24/10/2023, and the “Lifebility award” obtained on 17/05/2023). A detailed exploitation roadmap and business plan were developed for the nanocomposite hydrogel, paving the way for its future exploitation.
Results on the novel handheld arthroscopic device allowed filing a patent, publishing a paper on Ann. Biomed. Eng. and preparing another publication currently under review on Sci. Rep. The KPI was a usability score of at least 7 out of 10 by skilled surgeons. This objective was largely matched, with an average score of 8.6 out of 10. The technology is promising, and it is not far from having a possible commercial impact.
Results on a highly controlled ultrasound stimulation platform allowed filing a patent and publishing two papers: one on its validation, on Ultrasonics, another one on its direct use on macrophages, on APL Bioeng. All KPIs (broad range of frequencies and intensities and a dose error < 2.5%) were matched.
The efforts on a smart wearable brace for therapy delivery and monitoring, in an internet-of-things framework allowed filing a patent, publishing a paper on Sci. Rep., another paper on IEEE Transl. Eng. Health Med. and preparing another publication currently under review on IEEE Open J. Eng. Med. Biol. The KPI was a usability score of at least 7 out of 10 by patients. The average score achieved was 8.8 out of 10. A start-up company was founded based on these results. It will pursue its commercial exploitation.
Dissemination activities were rich and successful. The project website received, on average, 500 visits per month, with visitors from 72 different countries. The Consortium organized four scientific workshops/simposia and participated in several events, with a total of 69 oral or poster presentations delivered. Overall, 23 publications were achieved on ISI journals. This constitutes an impactful result in the scientific community, covering all scientific and technical aspects of the project. Furthermore, the Consortium published eight conference proceedings and 28 conference abstracts.
The project communication campaign was intense and impactful, with several initiatives that reached a large number of citizens. An interview of the project Coordinator at the SuperQuark program reached 2.263.000 people (13% share of Italian TV audience on that day). Concerning social media, 953 followers were achieved on Facebook and Twitter. The Consortium members made 7 TV/radio interviews, 19 press news and 28 internet news. Four large non-technical events were organized to communicate the project concept and results to the general public.
The project achieved excellent exploitation outcomes. The Consortium filed a large portfolio of patents (4 patents: WO2020174395A1, WO2021014331A1, WO2022074632A1, WO2023275771A1), protecting the IP generated in a thorough way. A start-up was founded (MyEcho S.r.l. https://www.myechosrl.com/) which was born grounded on results obtained during the project course concerning wearable braces. The start-up has already received two national prizes (the “Most innovative spin-off company in Tuscany award”, assigned during the “Start Cup Toscana” event on 24/10/2023, and the “Lifebility award” obtained on 17/05/2023). A detailed exploitation roadmap and business plan were developed for the nanocomposite hydrogel, paving the way for its future exploitation.
The Consortium, at the end of the 5 years, demonstrated for the first time on animal models the efficacy of this new paradigm, which aims to be a game-changing approach in the field of osteoarthritis treatment. The updated results obtained at the end of the project confirm the potential of the proposed approach. Exciting in vitro results, published in ACS Nano, confirmed an important boost in chondrogenesis due to the combination of piezoelectric nanomaterials and ultrasound waves, as well as anti-inflammatory effects. These effects were confirmed by in vivo tests on osteoarthritis animal models. This represents a considerable jump ahead in the field. The 4 patents filed by the Consortium also guarantee a good portfolio of IP-protected technologies, which maximize their possible future exploitation. The potential impact of the project is enormous, as confirmed by the several hundreds of end-users that contacted the project partners, urgently asking for a solution to osteoarthritis. A future clinical translation of the project results will allow concretizing this potential.