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Next generation hydrogel for bone tissue engineering

Alternative title: Smarte hydrogeler for å stimulere beintilvekst

Awarded: NOK 2.3 mill.

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Project Period:

2021 - 2024

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Treatments of musculoskeletal defects is a major burden to the healthcare providers, and with an aging population it is expected to increase. This gives an extraordinary demand for improved medical devices to treat these defects, preferably through minimally invasive procedures with shorter hospitalization time. Simultaneously the newest EU regulations for medical devices limits the use of human and animal derived products, exacerbating the need for potent, synthetic biomaterials. In this project we aim to develop an injectable hydrogel for rapid bone regeneration. To stimulate the bone growth, we will use a cell-friendly polymer with inorganic particles and the bioactive biomolecule incorporated. The project is lead by Material Biomimetic AS, who leverage their expertise within biomaterials and product commercialization. The collaboration partners are Politecnico di Milano who contributes with hydrogel expertise and The Institute of Clinical Dentistry, University of Oslo for their clinical knowledge and expertise of in vitro characterization of medical product. Various combinations of hydrogels and alternatives to the nucleating agents within the hydrogel have been assessed in the period. An advanced in silico modeling has been completed on how this system will affect biomineralization.

In this project, we aim to develop an injectable biocompatible hydrogel loaded with a bioactive peptide (NuPep™) that can be injected directly into the bone or at defect site to quickly regenerate bone. Injectable scaffolds play an important role in tissue regeneration since they provide numerous advantages over pre-formed scaffolds and are currently used for regeneration of craniofacial and dental tissues, which consist of alveolar bone, temporo-mandibular joint, periodontal ligament, dentin, and pulp. We aim hope that the gel developed can be used for this type of application, but also for orthopaedic application, which tends to be more technologically challenging. A very interesting orthopaedic application is intercage filling in spinal fusion, which is estimated to be a €1.15Bn European market that grows by more than 8% every year . Many hydrogels are used in synthetic ECM, some are even commercially available, like TrueGel3D, which is a blend of dextran, polyvinylalcohol and polyethyleneglycol (PEG). Gelation speed, gel stiffness and the density of cell binding motifs can be fine-tuned by adjusting the amount of cross-linker, while thiol-reactive cross-linkers, photo-, enzyme or thermosensitive cross-linkers can be used to modulate the local network density to affect cell behaviour. There is not a universal hydrogel for every cell type, but synthetic gels offer consistency between experiments as fine-tuning of microenvironments around cells and tissue occurs. A very important aspect is the cross-linking of the gel. Hydrogels prepared by physically crosslinked methods are usually reversible gels and are relatively easy to produce without any crosslinking agents during synthesis process but are usually associated with a quick degradation. Alternatively, chemically crosslinked hydrogels are stable elements as the covalent bonds exist in between the polymer chains, giving them a longer degradation time.

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