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NANO2021-Nanoteknologi og nye materiale

Injectable biomaterials for dental tissue engineering

Alternative title: Injiserbare biomaterialer for dental vevsregenerasjon

Awarded: NOK 8.8 mill.

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Project Period:

2019 - 2023


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The InjecTE project aimed to develop and test injectable biomaterials that can direct the body's own stem cells to repopulate, differentiate and replace lost tissue around and in the tooth root itself. The classic therapeutic approaches are to remove and inactivate, in order to eliminate inflammation and stop tissue destruction, rather than to facilitate endodontic and periodontal tissue regeneration. Such a strategy does not lead to the regeneration of lost tooth tissue, which can affect the vitality and lifespan of the tooth. Although progress has been made, rebuilding the structure and function of lost tooth tissue is challenging. Injectable materials offer several advantages in endodontic and periodontal regeneration, as these can easily infiltrate the tissue space that is empty after root canal or periodontal treatment. Furthermore, the materials can act as a delivery system for cells and stimulants, directly reaching the diseased site with minimal invasiveness. The ideal material should be biocompatible and degradable, but durable enough that the body's own cells have made enough extracellular matrix to take over the task. Various compositions of injectable cross-linked nanocomposite biomaterials have been developed and characterized. For endodontic regeneration, a hydrogel with varying degrees of hyaluronic acid and components that stimulate mineralization was chosen. The effect of the various combinations on pulp cells was tested with traditional in vitro methods, with simulated body fluid, and in root canals from extracted teeth. The gel solution which proved to be optimal with regard to cell growth and mineralization in vitro, did not work as well in vivo. Signs of a cytotoxic reaction lead further testing of a gel variant without a cross-linker, and with stimulating agents. In vivo endodontic evaluation, and characterization of ingrown cells, blood vessels/nerves is currently ongoing. For periodontal regeneration, a bioactive hemostatic cryogel based on platelet lysate (PL) and aldehyde-functionalized cellulose nanocrystals (a-CNC) has shown promise. Periodontal ligament cells stimulate osteogenic differentiation by specific combinations of PL and CNC in vitro. In blood, a tendency to swelling of the cryogel is observed, which is not optimal in a clinical setting. Various optimizations of the gel were tested to avoid errors, but the experiments did not give promising enough results until this was tested in vivo.

The project goals were to develop and characterize the in vitro and in vivo effects of new therapeutic strategies inducing endodontic and periodontal regeneration Various variants of biocompatible, biodegradable and injectable hydrogens were generated, and the effects were tested in vitro on commercially available human primary cells and in vivo in various experimental models. The project has been very interdisciplinary, and involvement and advice from clinical stakeholders, employees at the Faculty of Dentistry/UiO, has been obtained throughout the project period. The results in this project has been disseminated to academia and the scientific community through numerous open access high-impact peer-reviewed scientific publications. Due to the pandemic, the number of presentations at international conferences have, however, been fewer than anticipated. The pandemic caused problems related to our plans related to physical meetings and mobility between partners, organization of specific symposiums in the area of the project proposal etc. We hope that the results communicated through this project will lead to the development of newer treatment strategies in dentistry, and thus have an impact on the preservation of teeth and improvement of oral health of the patients

InjecTE is a multidisciplinary project assembling international leading researchers in biomaterials science, tissue engineering and regenerative medicine, molecular and cell biology, dentistry, and industrial development of biomaterials and medical devices aiming at developing and testing new advanced biomaterials for periodontal and endodontic regeneration. Such materials would have a huge impact in the dental biomaterials field since they would change current healing therapies to regenerative outcomes. These would render the patients better treatments and higher satisfaction with the dentists. Therefore, if successful, the project outcomes will have an enormous social impact and potential for commercialization. The project plan comprises the following tasks, to develop and characterize injectable crosslinkable biomaterials; evaluate the differentiation of stem cells and potential to regenerate dental tissues in vitro; study endodontic regeneration and periodontal regeneration in vivo. The project plan also comprises dissemination and communication activities, an efficient project management and a commercialization strategy. This project is well-timed, fundamental, in the forefront of current international research in this field, and has societal implications. This project is highly interdisciplinary, involving all aspects from basic science to enhance human health and well-being. Each group involves one young talented researcher and international experience for the young researchers is planned.

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Funding scheme:

NANO2021-Nanoteknologi og nye materiale