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Regenerative Medicine Innovation Crossing - Research and Innovation Staff Exchange in Regenerative Medicine

Periodic Reporting for period 2 - REMIX (Regenerative Medicine Innovation Crossing - Research and Innovation Staff Exchange inRegenerative Medicine)

Reporting period: 2019-11-01 to 2023-04-30

REMIX Network is becoming a leading open-ended hub at international level on research and young researchers training on use of natural materials to fabricate innovative strategies to induce human tissue regeneration after trauma or specific pathologies, by designing future products based on natural resources and sustainable, low cost and available to a large population. In addition, we define and fabricated 3D in vitro models that can allow the reduction of animal tests and also predictive asses for the evaluation of drugs without having to resort to animal tests or to model diseases and their mechanisms (such as tumor models).
Training of students at all levels and young researchers was one of our priority actions, in order to provide them knowledge and experience for a new professional profile in the field of tissue engineering and regenerative medicine. In particular, learning the relevance of a multidisciplinary and multi-cultural working environment, and its impact on their future career.
REMIX Network has investigated extensively the potentialities of materials of natural origin for use in the regeneration of human tissues for biomedical and diagnostic purposes and to design protocols that can be picked up and scaled up by the biotechnological industry. The research is performed with a multi-disciplinary approach, welcoming inputs from material engineering, physics, biology, chemistry, medicine, and computational modelling.
We choose to research sustainable materials isolated from natural resources (such as silk, collagen and keratin), comprising industrial and food wastes, eventually combined with natural pharmacological molecules with long tradition of use in Asian Traditional Medicine. We intended to explore this wealth of knowledge, testing them rigorously and following the international standards to find out which ones can actually be used in Regenerative Medicine.

The REMIX project has organized exchanges of researchers (mainly PhD students and young researchers) between partner universities to conduct joint scientific research and exchanges of practices and experiences aiming at the achievement of the project's objectives and developping a more international profile within their studies.
The research activities were focused on the investigations and the developments of natural materials which can be applied under the use of Tissue Engineering and Regenerative Medicine (TERM) based procedures. Following this main object, the work was performed as follows:
• The natural biomaterials were selected and processed by using different processing methodologies.
• The fabrications TREM bioactive scaffolds with defined biological and physical properties were made based on the selected materials.
• Protocols and standard procedures were defined and optimized for material processing and characterizations, scaffold fabrications, in vitro evaluations of the materials and scaffolds.
• The investigations on the effects of the scaffolds built by different materials on the differentiation of stem cells using different progenitor cells and considering tailored possible applications.
At the end of the project, 7 natural materials were selected, 16 blends were prepared and tested, 25 protocols and procedures were defined for material processing, scaffold fabrication and in vitro evaluations, and 10 3D- in vitro models were selected and tested. 16 papers were published under the project and 2 patents were proved and 1 patent is under preparation.
During the project, winter/summer schools, workshops, and seminars were organized by the consortium and more than 150 researchers were trained. 56 secondments were implemented, including 17 mobilities of PhD students and young researchers. This exchange provided opportunities to build their future careers, especially for whom came from Asia to Europe. The collaborations within the consortium also extended involving third parties, including other universities and research institutions.
The strategies developed by REMIX led to the development of new projects with the local governments and nations and a new Horizon 2020 project. The scientific results of the project were diffused to the scientific community and also to the general public, by presenting in public events, TV, seminars, lectures, workshops, and conferences. The knowledge developed during the project also brought new collaborations with companies, which showed potential translations to industries and the market.
The project has made progress beyond the current state-of-the-art,by succesfully design and fabricate the following protocols and systems:
• A novel cross-linking method of silk fibroin hydrogel was established by using Au nanoparticles with antitumor properties.
• A new composite system based on millimeter-sized spheres of beta-tricalcium phosphate, hydroxyapatite, alginate and silk fibroin, which could be used for bone tissue engineering applications.
• A double controlled dermal delivery system was designed. The system is built by natural polymer with nontoxic and good biocompatibility. The fabrication method is easy, fast and low cost, as well as the material.
• Keratin from camel hair and goat cashmere was extracted, and the characteristics (no literature before) of the soluble and insoluble keratin were evaluated. In vitro biological studies performed showed good bioactivity in both sources.
• A porous microsphere of silk fibroin and gelatin for cell carrier.
• Extraction procedures to obtain calcium phosphate (CaP) from black chicken bone.
• CaP from black chicken bone combined with gellan gum to obtain hybrid scaffolds for osteochondral defect regeneration.
• New injectable dexamethasone-cyclodextrin complexes-loaded gellan gum hydrogels were developed for cartilage regeneration.
• New hydrogels based on silk fibroin and gellan gum, which present adequate properties to regenerate cartilage.
• Innovative films based on hyaluronic acid and chitosan, with or without inorganic nanoparticles, were produced with distinct formulations with potential for bone regeneration purposes.
• A temperature triggered drug (Sea Buckthorn oil) releasing patch for wound healing.

The project had a strong impact on the scientific community:
• The natural or nature-inspired biomaterials for TERM were actively investigated and developed.
• Intensive collaborations were built among European and Asian experts with different academic, scientific, and industrial backgrounds.
• The aim of the build-up of a research hub of nature-derived biomaterials/constructs/strategies for TERM was also realized.

The social impact is mainly referring to raising awareness of the general public and how the scientific research could be applied towards industrial production:
• Improvement of the working and career prospects of the ESRs involved in the secondments.
• Some projects developed product prototype which is ready for technology transfer and new health related products were under the development.
• UNITN silk project with Rovereto Municipality is also a platform to develop new products silk-based medical grade and to translate research into market.
• During Prof. Claudio Migliaresi secondment in Mongolia at MUST (March 2023), the project strategies and results were reported at the local TV.
• Prof. Antonella Motta was interviewed on natural polymers used in medicine at RAI Trentino on 13 October 2022 at Trento RAI center.
Kaewprasit’s attendance to a training course on Biomaterials and Tissue Engineering (WP1)
Sahapaiboonkit, Yamdech and Raggio during labwork at UNITN Wp2-3)
Prof. Migliaresi sec at Chonbuk 2020
Final Workshop Braga April 2023 group photo
PA moment of the round table at TICME conference (WP7)
Profs Sorada, Aramwit and Ekthul secondment at UNITN
Group photo at TICME Conference in Trento (WP7)
Books from REMIX consortium 2020
Steering Committee meeting at UNITN (WP6)
Dr. Bonani and Dr Raggio sec at Chulalongkorn 2018
Meeting at Chulalongkorn University Thailand
Steering Committee meeting at Chulalongkorn University (WP6)

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