cmRNAbone - 3D Printed-Matrix Assisted Chemically Modified RNAs Bone Regenerative Therapy for Trauma and Osteoporotic Patients
Third-party funded project
Project title cmRNAbone - 3D Printed-Matrix Assisted Chemically Modified RNAs Bone Regenerative Therapy for Trauma and Osteoporotic Patients
Principal Investigator(s) Banfi, Andrea
Co-Investigator(s) Jaquiéry, Claude Armand
Schaefer, Dirk Johannes
Organisation / Research unit Departement Biomedizin / Cell and Gene Therapy (Banfi),
Bereich Operative Fächer (Klinik) / Chirurgische Forschung (Heberer)
Project start 01.01.2020
Probable end 31.12.2023
Status Active
Abstract

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.

Financed by Commission of the European Union
   

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10/08/2020