Norwegian Marine Biopolymers as Injectable Hydrogels for Tissue and Organ Repair – TUNIGUIDE

The project developed injectable, in situ gelling hydrogel formulations based on Norwegian marine biopolymers, tunicate nanocellulose fibrils and alginate, for tissue and organ repair and regeneration. Donor organ shortages are a serious global problem resulting in high mortality rates of people on transplant waiting lists and leads some people to obtain organs through illegal, unethical pathways. Tissue engineering, in which biomaterials are combined with cells, offers an alternative to help resolve this healthcare problem. We generated hydrogels, materials composed of a hydrophilic polymer network capable of high hydration that can be tuned to deliver therapeutic agents or cells to damaged sites. We assessed different variants of these nanocellulose/alginate hydrogels and evaluated their rheological properties, injectability, and, at site retention, both in vitro and in in vivo animal models. Our studies found that these hydrogels were qualified as biocompatible products, according to ISO 10993-5,12,20. The hydrogels also passed the tests for pathogenic micro-organisms (bioburden) and endotoxin detection, according to FDA and European Pharmacopeia standards. We also found that tunicate nanocellulose/alginate hydrogels were biocompatible in a Wistar rat study and were found to be non-irritant in comparison to controls of commonly used Gortex surgical meshes. In contrast to surgically implanted materials, injectable hydrogels provide new avenues of minimally invasive delivery that will reduce healing time, reduce scarring and decrease the risk of post-operative infections. Full realization of this approach will significantly lower costs for hospitals and result in less pain for patients. These are important translational aspects in bringing regenerative treatments into the clinic.

The biomaterials market driving tissue engineering is expected to grow to 207 billion USD by 2024. Through this project, we have developed 3 new versions of modified tunicate nanocellulose (TUNICELL) biomaterials. Two of these, TEMPO-mediated oxidized TUNICELL (TTC), and carboxymethylated TUNICELL (CTC) have now been released on the market. A third variant, periodate oxidized TUNICELL, to serve as a base platform for grafting of biologically active agents, is now undergoing scale up and quality control assessments with an anticipated market release in 2024. The ambition is to capture 5% of the biomaterial hydrogel market. For targeted end-user groups, hospitals, clinicians and patients, achieving project goals will reduce transplants and implants, lower costs, mean faster recovery and reduced pain for patients, require fewer skilled personnel and less specialized equipment in operating theatres and translate to easier adoption in medical billing practices. Through our project publication and outreach activities, the tissue engineering research community has been apprised of the advantages of using TUNICELL hydrogels in their applications and have developed competence in the use of such hydrogels. As a testament to this, 7 additional publications in internationally peer-reviewed journals, using TUNICELL variants, by early adopter groups outside of the project itself, have appeared during the project period. Broader societal impacts include development of marine biotech, stimulation of low trophic aquaculture, and with scale-up, opportunities to produce local, high value feed ingredients, advanced, sustainable biomaterials applications and reduced pressures on terrestrial land use. At the end of 2022, Ocean TuniCell AS was awarded the Bergen Commune company start-up prize, and the activities and results in the TUNIGUIDE project contributed towards reception of this award.

This project will develop biocompatible, injectable, in situ gelling hydrogel formulations based on Norwegian marine biopolymers, tunicate nanocellulose fibrils and alginate, for tissue and organ repair and regeneration. Donor organ shortages are a serious global problem resulting in high mortality rates of people on transplant waiting lists and leads some people to obtain organs through illegal, unethical pathways. Tissue engineering, in which biomaterials are combined with cells, offers an important alternative to help resolve this global healthcare problem. Hydrogels, materials composed of a hydrophilic polymer network capable of high hydration, yet retaining structural integrity, are attractive biomaterials in that they are biocompatible and can be tuned to deliver therapeutic agents or cells to damaged sites. Biocompatible hydrogels can act as scaffolds supporting growth of cells to promote tissue or organ repair. In contrast to surgically implanted materials, injectable hydrogels provide a new avenue of minimally invasive delivery that will reduce healing time, reduce scarring and decrease the risk of post-operative infections. Realization of this approach would significantly lower costs for hospitals and result in less pain for patients. These are important translational aspects in bringing regenerative treatments into the clinic and will involve development of biocompatible, GMP accredited biopolymers with application-specific, tunable properties. The project focus will be in tuning the injectability, in situ gelling properties and release rates to guide bioactive components for specific therapeutic applications. Studies designed to control fibril lengths, orientation/alignment, surface modifications and crosslinking kinetics, will be carried out to optimize flow and diffusion properties for specific tissue applications. Selected preclinical assessments will be carried out in 3 different tissue types.