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3D Printed-Matrix Assisted Chemically Modified RNAs Bone Regenerative Therapy for Trauma and Osteoporotic Patients

Project description

Chemically modified RNAs and 3D printing in bone regenerative therapy

The ultimate goal of this EU-funded cmRNAbone project is to develop reliable bone regenerative technology to treat widespread bone traumatic injuries and osteoporosis-induced bone fragile fractures. Researchers aim to create a novel bone regenerative therapeutic approach using a combination of chemically modified RNAs and 3D printing technologies. Chemically modified RNAs of the growth factors targeting neurogenesis, vasculogenesis and osteogenesis will be synthesised together with vectors based on lipids and polysaccharide nanocapsules for the RNAs' delivery. Delivery of the vectors will be achieved with a 3D bioprinting process using hyaluronan-calcium phosphate biomaterial ink that can be loaded with vectors and able to be released later. This bio-ink will provide osteoinductivity and laminin-derived peptides for guiding sensory neurons and endothelial cells' ingrowth. The project aims to achieve preclinical proof of concept for selected drug candidates and prepare a first-in-human clinical trial.

Objective

Due to life style changes and ageing of our industrialized nations, bone traumatic injuries and osteoporosis induced fragile fracture are an enormous medical and socio-economic challenge. State-of-the-art therapies have failed until now in keeping their promises of reliable bone regenerative solutions.
The cmRNAbone project aim to create a novel bone regenerative therapeutic approach based on combination of chemically modified RNAs (cmRNAs)-vectors embedded in a 3D-printed guiding biomaterial ink tailored to patients need. To achieve our goal, sema3a, vegf, pdgf-bb and bmp7 cmRNAs targeting neurogenesis, vasculogenesis and osteogenesis will be synthesized, vectors based on lipids and polysaccharide nanocapsules for the delivery of cmRNAs will be developed. A functional Hyaluronan-Calcium Phosphate biomaterial ink that 1) can be loaded with cmRNAs-vectors and release them, 2) having intrinsic osteoinductivity and presenting laminin-derived peptides for guiding sensory neurons and endothelial cells ingrowth, and 3) being amenable to an extrusion-based 3D-bioprinting process will be formulated in conjunction to a 3D-printer for fabrication of patient specific regenerative solution. In the following step, a large effort will focus on deciphering regenerative mechanisms and optimizing dosage and ratio of cmRNAs, loading of cmRNAs-vectors in the ink, 3D-printing, etc, to demonstrate regenerative capabilities in vitro and in vivo. Selected candidate formulations will be taken to clinically relevant preclinical proof of concepts. Finally, an overreaching effort on preparing a 1st in human trial will be taken, consisting on partners facilities auditing and clinical experts group support, etc, to ensure that GMP-like production for all regenerative tools, and regulatory and commercial strategies are realized.

Call for proposal

H2020-SC1-BHC-2018-2020

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Sub call

H2020-SC1-2019-Single-Stage-RTD

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Coordinator

AO-FORSCHUNGSINSTITUT DAVOS
Net EU contribution
€ 710 750,00
Address
Clavadelerstrasse 8
7270 Davos platz
Switzerland

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Region
Schweiz/Suisse/Svizzera Ostschweiz Graubünden / Grigioni / Grischun
Activity type
Research Organisations
Links
Other funding
€ 0,00

Participants (13)