Periodic Reporting for period 1 - NANOREMEDI (Functional Nano-Scaffolds for Regenerative Medicine)
Reporting period: 2022-09-01 to 2024-08-31
The Horizon Europe MSCA-Doctoral Network NanoReMedi “Functional Nano-Scaffolds for Regenerative Medicine” is run by an international consortium of universities in cooperation with the private sector. It provides innovative PhD level training on nanomaterials through a highly multidisciplinary approach involving several of state-of-the-art technologies and methodologies (computational and synthetic chemistry, nanomaterial production and characterization).
The research focus is on nanomaterials for regenerative medicine, a strong potential area for training a new generation of doctoral candidates (DCs) as future professionals crucial in the European nanotechnology field. To provide world-class training to 13 DCs, three case studies in regenerative medicine were selected:
1. Tissue engineered vascular grafts to replace damaged peripheral arteries.
2. Stem-cell based regenerative medicine for bone and cartilage repair
3. Facing with implantation failure of engineered tissues/scaffolds.
Nanoremedi website https://www.nanoremedi.eu/(opens in new window)
The research focus is on nanomaterials for regenerative medicine, a strong potential area for training a new generation of doctoral candidates (DCs) as future professionals crucial in the European nanotechnology field. To provide world-class training to 13 DCs, three case studies in regenerative medicine were selected:
1. Tissue engineered vascular grafts to replace damaged peripheral arteries.
2. Stem-cell based regenerative medicine for bone and cartilage repair
3. Facing with implantation failure of engineered tissues/scaffolds.
Nanoremedi website https://www.nanoremedi.eu/(opens in new window)
SCIENTIFIC research. NanoReMedi started with design and synthesis of libraries of peptides/peptidomimetics, i.e. peptides containing non-natural amino acids, or specific scaffolds, divided into two categories: i) peptides from natural amino (Aa) inspired by specific biological functions, or to be functionalized with different scaffolds to favor self-assembly; ii) peptidomimetics prepared from non-natural Aas tested to generate electro-spun fibers, gels, nanoparticles. The nanomaterials are addressed to four applications:
a) Cardiovascular tissue regeneration: Innovative peptide-based coatings, resisting to bacterial attachment, facilitating targeted cells adhesion or avoiding vascular obstruction, were prepared and linked to or blended with biocompatible/biodegradable polymers to improve fiber performance, elasticity/mechanical strength, generating improvement of some biological functions.
b) Hydrogels for cartilage: a series of peptides with chondrogenic/osteogenic activities were synthesized and functionalized with a sylil group for hydrogel networks. Furthermore, biodegradable silylated polymers were prepared to crosslink them into chemical hydrogels. Biomimetic hydrogels with good stability obtained by the sol-gel process will be tested for stem-cell based regenerative medicine.
c) Biofilm prevention: the development of innovative peptide-based coatings, serving to increase resistance to bacterial attachment facilitating targeted adhesion of muscle/endothelial cells, were prepared.
d) To deliver antimicrobial molecules, electrically responsive polymers/peptidomimetics were selected. The outcome of this research extend beyond conventional drug delivery methods, presenting a pathway towards overcoming challenges associated with antibiotic resistance.
TRAINING. The next generation of researchers requires a common knowledge and language for nanotechnology applied to nanomedicine. NanoReMedi organized multidisciplinary courses, workshops and Summer School to create future skilled researchers on nanotechnology.
a) Cardiovascular tissue regeneration: Innovative peptide-based coatings, resisting to bacterial attachment, facilitating targeted cells adhesion or avoiding vascular obstruction, were prepared and linked to or blended with biocompatible/biodegradable polymers to improve fiber performance, elasticity/mechanical strength, generating improvement of some biological functions.
b) Hydrogels for cartilage: a series of peptides with chondrogenic/osteogenic activities were synthesized and functionalized with a sylil group for hydrogel networks. Furthermore, biodegradable silylated polymers were prepared to crosslink them into chemical hydrogels. Biomimetic hydrogels with good stability obtained by the sol-gel process will be tested for stem-cell based regenerative medicine.
c) Biofilm prevention: the development of innovative peptide-based coatings, serving to increase resistance to bacterial attachment facilitating targeted adhesion of muscle/endothelial cells, were prepared.
d) To deliver antimicrobial molecules, electrically responsive polymers/peptidomimetics were selected. The outcome of this research extend beyond conventional drug delivery methods, presenting a pathway towards overcoming challenges associated with antibiotic resistance.
TRAINING. The next generation of researchers requires a common knowledge and language for nanotechnology applied to nanomedicine. NanoReMedi organized multidisciplinary courses, workshops and Summer School to create future skilled researchers on nanotechnology.
US National Institute of Health defined regenerative medicine as “the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects”. People aged over 65 are expected to make up more than 40% within 20 years increasing the demand for regenerative medicine. Nanotechnology is crucial for restoring functions and regeneration of diseased tissues/organs. The case studies selected for NanoReMedi contribute to new nanomaterials addressing specific problems:
1. Biodegradable composite vascular grafts to replace damaged peripheral arteries.This occlusive disease is one of the major cardiovascular disease (annual mortality: 23.3 million by 2030; involves 4-12% of adults, 55-70 years-old; burden of mortality: 10-15%). Treatment for patients unresponsive to medical therapy relies on costly surgical or endovascular revascularization by autologous vein by-pass surgery, requiring an invasive harvest, limited by low availability of autologous vessels. Synthetic vessels, matching the native tissue mechanical/structural properties, represents a more-compliant/cost-effective improved strategy. Advanced materials mimicking the mechanical/biologic properties of the vascular walls-forming tissues represent a viable solution, providing vascular surgeons with a source of “physiological” safe/durable conduits.
2. Stem-cell based regenerative medicine for bone and cartilage repair. Treatment of full-thickness cartilage defects, which cartilage/sub-chondral bone damaged, is a difficult challenge. Typical treatments involve repeated corticosteroids and visco-supplementation injections in joints, providing temporary pain relief and functionality improvement, cell therapies promoting cartilage regeneration, but with some limitations due to phenotype stability and large production issues. Mesenchymal stem cell-based therapies are an attractive alternative. Novel biomimetic hydrogels with finely tunable properties are attractive alternatives: osteochondral scaffolds stimulating the regeneration of the damaged tissues with long lasting therapeutic effects would be most cost-effective.
3. Facing with implantation failure. Bacterial infections affect over 250 million people worldwide per year. Recently, the World Health Organization published a list of 12 different bacterial strains resistant to many antibiotics. For implants, these strains may lead to the formation of a biofilm, providing the bacteria with superior survival properties, including resistance to antibiotics, inducing severe infection and implant failure. Effective counteraction is based on peptide nanostructures, working as both antimicrobials and electro-responsive carriers, preventing antibiotic resistance. The combination of antimicrobial peptides and peptide-based nanocarriers is expected to overcome the main drawbacks of the current therapeutic approach.
1. Biodegradable composite vascular grafts to replace damaged peripheral arteries.This occlusive disease is one of the major cardiovascular disease (annual mortality: 23.3 million by 2030; involves 4-12% of adults, 55-70 years-old; burden of mortality: 10-15%). Treatment for patients unresponsive to medical therapy relies on costly surgical or endovascular revascularization by autologous vein by-pass surgery, requiring an invasive harvest, limited by low availability of autologous vessels. Synthetic vessels, matching the native tissue mechanical/structural properties, represents a more-compliant/cost-effective improved strategy. Advanced materials mimicking the mechanical/biologic properties of the vascular walls-forming tissues represent a viable solution, providing vascular surgeons with a source of “physiological” safe/durable conduits.
2. Stem-cell based regenerative medicine for bone and cartilage repair. Treatment of full-thickness cartilage defects, which cartilage/sub-chondral bone damaged, is a difficult challenge. Typical treatments involve repeated corticosteroids and visco-supplementation injections in joints, providing temporary pain relief and functionality improvement, cell therapies promoting cartilage regeneration, but with some limitations due to phenotype stability and large production issues. Mesenchymal stem cell-based therapies are an attractive alternative. Novel biomimetic hydrogels with finely tunable properties are attractive alternatives: osteochondral scaffolds stimulating the regeneration of the damaged tissues with long lasting therapeutic effects would be most cost-effective.
3. Facing with implantation failure. Bacterial infections affect over 250 million people worldwide per year. Recently, the World Health Organization published a list of 12 different bacterial strains resistant to many antibiotics. For implants, these strains may lead to the formation of a biofilm, providing the bacteria with superior survival properties, including resistance to antibiotics, inducing severe infection and implant failure. Effective counteraction is based on peptide nanostructures, working as both antimicrobials and electro-responsive carriers, preventing antibiotic resistance. The combination of antimicrobial peptides and peptide-based nanocarriers is expected to overcome the main drawbacks of the current therapeutic approach.