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Materialteknologi

Limb wounds in horses are common, however healing is exceedingly slow and fraught with complications. Contrary to body wounds, limb wounds demonstrate only a small amount of wound contraction. The specialist procedure of applying split-thickness skin grafts to limb wounds stimulates wound contraction by unknown mechanisms. The objective of this project is to identify those mechanisms to develop a treatment strategy for equine limb wounds for use in general  practice. Limb wounds are severely impacting animal welfare due to an extended healing/treatment duration, and the risk of euthanasia due to a poor functional outcome. By stimulating wound contraction, healing time will be reduced, and the functional outcome improved, directly benefitting the welfare of wounded horse and reducing treatment cost for the owner. Aim: To identify dermal components stimulating wound contraction, and to develop this knowledge into future state-of-the-art treatment of equine limb wounds for use in general practice. Hypotheses: i) Application of dermal fractions to collagen gels seeded with equine fibroblasts will increase gel contraction in vitro; ii) Application of dermal fractions to experimental limb wounds in vivo, will increase wound contraction resulting in a faster healing time versus wounds treated by conventional methods. Methods: i) The contractile effect of different dermal components will be assessed in a collagen gel/ fibroblast model; ii) Identified dermal components will be tested in a standardized experimental limb wound model in vivo (n=5). Ultimately, results from this project are expected to improve wound treatment in horses, directly impacting animal welfare by reducing healing time and improving the functional outcome of wounded horses. This will also directly benefit horse owners and caretakers and making veterinarians able to offer better treatment solutions.

HESTEFORSK - Raskere og bedre sårheling hos hest med autologe hudkomponenter

En av de vanligste, men minst studerte, utfordringene med å bli eldre er problemer med å kommunisere. Mange eldre sliter spesielt med pragmatiske ferdigheter, som å forstå undertekst, eller tilpasse det de sier til personen de snakker med. 

La oss si at en lege må gi en alvorlig beskjed til en pasient. For å gjøre det litt lettere å takle, bruker legen vagere språk, som "kanskje" i stedet for "sannsynligvis". Mens yngre voksne ofte tar hensyn til høflighetsstrategier i måten de tolker det som blir sagt på, har eldre ofte vanskelig for å forstå når noen snakker indirekte. Mange eldre voksne har vanskelig for å forstå ikke-bokstavelig språk og kan misforstå alvorlighetsgraden av diagnosen. Dette kan påvirke beslutningen deres om behandling, noe som kan føre til utilsiktede konsekvenser. 

Siden god kommunikasjon er viktig både i viktige medisinske samtaler og i hverdagen, er det viktig at vi finner ut hva som gjør at eldre kan ha vansker med å forstå og bli forstått. RESILIENCE skal hjelpe til med denne utfordringen ved å samle data om praktiske, kognitive og språklige ferdigheter hos voksne i alderen 18-90 år over tid. Dette vil gi oss en stor mengde data om pragmatiske, kognitive og språk ferdigheter og gjøre det tilgjengelig for forskning. Med denne dataen som grunnlag har vi følgende mål: 

• Forstå hvordan praktiske evner endrer seg generelt gjennom voksenlivet. 
• Finne ut hvilke mekanismer som påvirker pragmatiske evner på forskjellige tidspunkter i livet.
 • Utvikle en teoretisk modell som forklarer hvordan pragmatiske ferdigheter endrer seg med alderen.
 • Lage algoritmer som kan forutsi hvordan pragmatiske evner vil utvikle seg for enkeltpersoner i årene som kommer. 
• Utvikle og teste et verktøy som kan måle pragmatisk helse (både pragmatiske ferdigheter og deres underliggende mekanismer), noe som kan åpne  for å iverksette tiltak. 

Dette vil gi oss muligheten til å forstå bedre hvordan folk kan utvikle pragmatisk resiliens gjennom livsløpet.

A cornerstone of human communication is our reliance on pragmatic skills to guide linguistic interactions (e.g., reasoning about others' mental states to bridge the gap between what is said and intended in conversation). However these skills are highly sensitive to age-related decline, leading to miscommunication and uninformed decision making in the older adult population. This raises an important question, one which has puzzled linguistics and psychologists for decades: if pragmatic competence is fundamental to communication, why do individuals vary so much in this capacity? 

Traditionally, psychologists have approached pragmatic competence from a cognitive angle, reasoning that individual differences in executive functions (i.e., the cognitive skills associated with goal-directed actions) are what underlie effective pragmatic behavior. In a similar vein, language scientists have taken a linguistic approach, reasoning that one’s language background (e.g., the frequency with which individuals shift between languages) shapes pragmatic skills by enhancing sensitivity to the communicative context. This focus on either cognitive or linguistic influences has resulted in two expansive yet disparate areas of research.

RESILIENCE will unite these disciplines to pursue a longstanding debate on what underlies pragmatic resilience and decline using a large-scale, interdisciplinary and longitudinal approach. By gathering data on adults' (ages 18-90) pragmatic, cognitive and language skills over multiple time points, we will develop a comprehensive theoretical model that explains how cognitive and linguistic systems interact to shape pragmatic competence as we age, and create algorithms that predict the trajectory of an individual’s pragmatic abilities in upcoming years. Based on these results we will design a multidimensional tool that detects the earliest signs of pragmatic deficits, leading to future interventions, allowing us to uncover the paths to pragmatic resilience.

Uncovering the paths to pragmatic resilience

Hovedmålet med kreftbehandling er å eliminere kreftceller og dette er tradisjonelt oppnådd ved kirurgi, bruk av giftige medikamenter (cellegift) og stråling. En ny og betydningsfull tilnærming til kreftbehandling kalt immunterapi, har derimot fått mye oppmerksomhet det siste tiåret; Her forsøker leger og forskere å utnytte immunsystemet vårt for å målrettet  ødelegge kreftceller. En nøkkelaktør i denne banebrytende tilnærmingen er en gruppe «drapsmenn» i immunsystemet kjent som cytotoxiske T-lymfocytter (CTL-er). Disse cellene har en bemerkelsesverdig evne til å oppdage kreftceller ved å gjenkjenne unormale molekyler på overflaten av kreftcellene - molekyler som friske celler ikke har. Når CTL-er gjenkjenner kreftcellene ødelegger de dem ved å frigjøre giftige molekyler som initierer kreftcellenes selvdestruksjon. 
 
Selv om betydelige innsats har blitt dedikert til å forstå hvordan CTL-er aktiveres og hvordan de gjenkjenner kreftceller, vet vi mindre om de påfølgende hendelsene inne i kreftcellene som fører til deres død. Fra før vet vi at CTL-er kan initiere to forskjellige typer celledød i kreft: den første, kalt apoptose, er en stille og ordnet prosess der kreftcellene krymper og brytes opp uten å varsle immunsystemet; den andre, kalt pyroptose, er en mer dramatisk prosess som involverer dannelse av åpninger i cellemembranen, noe som fører til at cellene svulmer opp og sprekker. Under denne cellebristen blir innholdet inne i cellene frigitt i omgivelsene, og dette kan fungere som 'faretegn' som kan stimulere en sterkere immunrespons mot kreftcellene. Betydningen av denne cellebristen for å forsterke anti-tumorresponsene vil bli undersøkt i dette prosjektet. 
 
Videre er vi fascinert av muligheten for å avdekke ytterligere, ennå ukjente, former for celledød indusert av CTL-er. Utforsking av disse dødsrelaterte prosessene i kreftcellene kan potensielt øke effektiviteten av immunterapi og bidra betydelig i den pågående kampen mot kreft.

The primary goal of most cancer therapies is to induce cancer cell death. Immunotherapy relies on the cytotoxic activity of lymphocytes such as natural killer cells (NKs) and cytotoxic T lymphocytes (CTLs) to achieve this. While a significant amount of research in immunotherapy focuses on the events within cytotoxic lymphocytes or at the interface between cytotoxic lymphocytes and cancer cells, less is known about the molecular mechanisms that orchestrate cancer cell death, particularly in the case of CTL-mediated death.
CTLs are known to induce two types of cell death in cancer: non-inflammatory apoptosis and proinflammatory pyroptosis. Pyroptotic cancer cells release proinflammatory signals that attract immune cells to the tumor site, thereby enhancing the anti-tumor response. Cell lysis is a common outcome of pyroptotic cell death. It is unclear whether lysis can be decoupled from pyroptosis in cancer cells and whether the proinflammatory properties of pyroptotic cancer cell death depend on lysis. Moreover, it remains unknown whether CTLs can induce other forms of cell death in cancer, apart from apoptosis and pyroptosis.
Studying the mechanisms of CTL-mediated cancer cell death is challenging because CTLs selectively target cells expressing specific antigens. However, given the critical role of CTLs in immunotherapy, it is essential to deepen our understanding of CTL-induced cancer cell death.
This project aims to develop novel methodologies to investigate the death mechanisms that are initiated by CTLs. In addition, we will identify new pathways and mediators involved in CTL-induced cancer cell death. Furthermore, we will assess the contribution of proinflammatory cell death and lysis in promoting anti-tumor responses in vivo. Overall, this research will improve our knowledge of the molecular mechanisms of CTL-mediated cancer cell death and potentially reveal novel targets to enhance the efficacy of cancer immunotherapy.

T-cell-mediated proinflammatory cell death and lysis in cancer

Sink er et essensielt mikronæringsstoff som kreves for funksjonen til hundrevis av proteiner involvert i et bredt spekter av biologiske prosesser. Etter inntak av sink fra kosten reguleres nivåene i kroppen nøye gjennom absorpsjon, sekresjon og ekskresjon via spesialiserte proteiner, såkalte sinktransportører, i tarmen. Enhver ubalanse er skadelig for menneskers helse, spesielt er tarmen følsom for sinkfluktuasjoner, hvilket påvirker tarmbarrieren og kan føre til inflammatoriske sykdommer og kreft i tarmen. 
På molekylært nivå er de presise mekanismene som styrer funksjonen til de ulike sinktransportørene fortsatt uklare. Hos mennesker finnes det over tjue slike proteiner, og de fleste inneholder områder rike på aminosyren histidin. Disse histidinene mistenkes å spille en avgjørende rolle i å binde sink. Nylig oppdaget vi et enzym som modifiserer disse områdene ved å sette metylgrupper på histidin, og viste at metylerte histidiner har en lavere affinitet for sink. Dette prosjektet har som mål å identifisere nye mekanismer som regulerer sinknivåer gjennom histidinmetylering av sinktransportører, å utvikle forskningsverktøy for effektiv studie av histidinmetylering, og å legge grunnlaget for nye behandlinger av tarmsykdommer.

The delicate balance of zinc levels in the body is essential for human health. Zinc is absorbed and excreted via intestinal zinc transporter proteins, and perturbations of this process are associated with pathologies, including inflammatory diseases and cancers of the bowel. The precise molecular mechanisms regulating zinc transport, however, remain a major knowledge gap. Based on the recent discovery of an enzyme methylating histidine residues in zinc transporters, and drawing on preliminary findings which demonstrate reduced affinity of methylated histidines to zinc, this project aims to identify novel mechanisms regulating zinc homeostasis through histidine methylation. We will examine the regulation and effect of histidine methylation on zinc transport in intestinal cell culture and organoids, and examine how knockout of the methylhistidine-generating enzyme affects the integrity and pathology of the intestinal tract in mouse models. In addition, we will identify reader proteins specifically recognizing methylhistidines and develop anti-methylhistidine antibodies and inhibitors to use as tools for detection, enrichment, and inhibition of histidine methylation. Such tools are urgently needed by the international research community, as none are currently available commercially. Overall, this project will lead to great advances in the field of protein regulation, and may uncover novel mechanisms in intestinal zinc transport and pathology.

Zinc transport regulation through histidine methylation

Noen av oss tåler stressende livshendelser godt. Andre derimot utvikler vedvarende fysiske og psykiske plager som følger av stress. Hvor godt vi håndterer stress avhenger av et komplekst samspill mellom miljøfaktorer, sosiale forhold, biologisk sårbarhet og indre motstandskraft. Forskning på stressreaksjonene til dyr og pasientgrupper som til vanlig lever under mye stress viser at en gruppe signalstoffer i kroppen som aktiverer det samme hjernesystemet som cannabis – endocannabinoidene – kan begrense styrken på stressreaksjoner og bidra til at man raskere kommer seg til hektene. I dette prosjektet skal vi undersøke hvordan mestring av stress på kort og lang sikt henger sammen med nivåer av endocannabinoider i kroppen for å forstå hvorfor noen personer er mer motstandsdyktige mot stress enn andre. I den ene studien følger vi pasienter som skal gjennomgå en stressende, men veldig vanlig, situasjon: kirurgi. Her måler vi pasientenes opplevelse av stress, samt mentale og fysiske helse, fra tiden før til to år etter operasjonen og undersøker hvordan dette henger sammen med nivåene deres av endocannabinoider og andre stresshormoner. I den andre studien bruker vi data fra et eksperiment hvor deltakerne har blitt utsatt for psykososialt stress til å undersøke om endocannabinoidnivået deres påvirker hvordan de reagerer på stress, og om stresset i seg selv kan påvirke kroppens produksjon av endocannabinoider. Til syvende og sist er målet med studien å vurdere hvorvidt målinger av endocannabinoidnivåer kan brukes til å forebygge helseplager og til å evaluere behovet for økt oppfølging etter alvorlig stressende påkjenninger i livet.

In the face of major life stressors, some individuals cope well whereas others develop ill health and long-term adverse outcomes. Predicting who needs additional support in response to major life stressors is essential for targeted prevention and more efficient allocation of resources. The endocannabinoid system is emerging as a promising target for understanding vulnerability and resilience to stress. This system appears to buffer stress in two ways: by limiting the magnitude of the stress response, and by facilitating recovery after a stressful event. While the early findings are intriguing, they mainly stem from studies in rodents and small clinical groups with high stress burden. What role endocannabinoids have more globally for human resilience, health and well-being remains elusive. 

In this project we address this gap by leveraging comprehensive experimental and clinical data on two potent stress models: psychosocial stress and surgery. Drawing on these unique datasets, which combine experimental control with ecological validity, we will decipher how endocannabinoid levels influence people’s stress response and recovery across minutes, days, weeks and years. The project represents a novel directional shift for endocannabinoid research and will (i) determine the value of endocannabinoid levels as a biomarker to predict outcomes after surgery, (ii) quantify sex differences, (iii) assess endocannabinoid interplay with opioid analgesics, sex hormones and other stress markers (iv) spearhead open and reproducible science practices in endocannabinoid research, and (v) make this fine-grained and novel data available through an interactive web application. 

This project represents an ambitious effort to understand endocannabinoids’ role in stress resilience and will determine the value of endocannabinoids as a predictive biomarker and potential target for individualized treatment.

Deciphering endocannabinoid stress buffering in humans: 
Mechanistic and clinical investigations

Borderline Personality Disorder: Memory and Identity in Adolescence

BOLD MINDS aspires to enhance the understanding of vulnerability factors underlying the emergence of borderline personality disorder (BPD), with an ultimate aim of increasing the potential for young individuals to receive early, evidence-based help when their mental health is at risk. BOLD MINDS will achieve this by investigating whether disruptions in two aspects of autobiographical memory (AM), narrative identity (NI) and involuntary AM (IAM), are associated with BPD features and problem behaviours in adolescents concurrently and over time. In doing so, BOLD MINDS will strengthen the understanding of mechanisms underlying the emergence of BPD in adolescence and lay a groundwork for developing evidence-based early interventions for BPD. While currently limited, the study of AM in this field is essential for two reasons. Firstly, because the aspects of AM under investigation, NI and IAM, are known to be involved in identity formation and emotion regulation which represent two key psychological processes that are disrupted in adults with BPD and are linked to problem behaviours such as self-harm and suicidality. Secondly, because promising research is emerging on the use of AM targets in the treatment of emotional disorder in adults, and provides a strong model for future treatment development with vulnerable adolescents. In addition, this timely research program aligns with calls from international organizations to prioritize early interventions to promote adolescent mental health. BOLD MINDS will adopt and adapt state-of-the-art ecological momentary assessment and analytical techniques and work at the crossroads of clinical and cognitive psychological perspectives, allowing for a multidimensional approach to understanding BPD vulnerability. Training-through-research and formalized training of the experienced researcher will prepare her for a permanent academic position and the founding of her own research lab specializing in AM and early interventions for BPD.

Bilingual Experiences, Cognitive Ageing and underlying Mechanisms

The goal of the Bilingual Experiences, Cognitive Ageing and underlying Mechanisms (BECAME) project is to examine the functional neuroplastic mechanisms underlying mitigatory effects of bilingual experience on age-related cognitive decline. While evidence is available for structural brain changes supporting bilingualism-induced effects on cognitive aging (CA), functional mechanisms underlying such effects are not yet well understood. BECAME aims to fill this gap by investigating the trajectory of bilingualism-induced functional neuroplasticity across the adult lifespan (ages 18-85), crucially adopting an individual differences approach related to measurable degree of bilingual engagement. Importantly, although such benefits are thought to be rooted early in the lifespan, evidence for the timeframe and conditions of their early emergence is scarce. The choice of including the whole adult lifespan allows us to investigate these mechanisms and their emergence more directly from a lifespan perspective. I combine behavioral testing with brain recordings via electroencephalography (EEG). EEG is widely used in cognitive neuroscience to assess brain activity and the degree of communication between brain regions (functional connectivity) in response to stimuli and at rest. Combining behavioral and EEG modalities will allow me to test bilingualism’s effect on functional connectivity, as well as its consequences for functional efficiency, the minimum required neural activation to successfully perform a task. This will enable a detailed, evidence-based account of the protective effects observed in older-aged bilinguals, and how they are built from earlier life stages. By illuminating the relationship between multilingualism and resulting neurocognitive adaptations, BECAME will enable to capitalize on it as a health initiative, with manifold societal implications and the potential to be translated into actionable policies exploiting multilingualism to ameliorate effects of CA.

WHeelchair Activity Monitoring project (WHAM)

Wheelchair users (WCU) are three to five times more inactive than the general population, leading to a high risk of developing preventable secondary conditions. Although physical activity (PA) guidelines have been specifically developed for WCU, we lack systematic approaches to implement them in practice, as well as valid algorithms to monitor PA change in WCU through sensor-based solutions. Accordingly, the overall scientific aim of the WHeelchair Activity Monitoring project (WHAM) is to advance PA research and practice in WCU by developing valid digital markers for monitoring of and providing feedback on PA, paving the way for implementation and intervention. I will accomplish this through combining the complementary research fields of 1) behavioural intervention studies focusing on increasing PA in WCU (core competence University of British Columbia, UBC; outgoing phase) and 2) sensor-based PA monitoring (core competence Norwegian University of Science and Technology, NTNU; returning phase – consolidated by non-academic placement at Maastricht Instruments, which develop research prototypes including PA monitors). WHAM’s scientific aim is achieved through three objectives: 1) Measure the effect of a pragmatic exercise intervention trial on self-reported physical activity levels and cardio-respiratory fitness, 2) Develop valid algorithms for tracking PA markers in WCU, and 3) Co-create a framework that outlines how PA can be conjointly monitored and provided feedback on in WCU. This fellowship will enable me to become established as an internationally recognized researcher in the field of “physical activity and disability”, while bringing together ongoing national disjointed research activities in this field. Altogether, my overall ambition is to contribute to reducing inequalities in daily-life participation among WCU compared to the rest of the population.

Despites dental pulp capping materials should meet the certain requirements, the available materials have one or more shortcomings—poor biocompatibility and rheological properties, fail to maintain pulp vitality and to simulate reparative dentine formation and expensive etc. Mineral trioxide aggregate (MTA) is widely used material because of its beneficial properties. However, its composition bismuth oxide, which is suspectable to toxicity, has an impact on rheological properties. This emphasizes the necessity of looking for inexpensive alternatives to materials that meet the specifications. This project's goal and novelty are to investigate the potential processing of the dental pulp capping cement, which is made of strontium silicate (SrSiO3), strontium fluoride (SrF2), piezoelectric material (PZM) and tricalcium silicate (Ca3O5Si) and its rheological properties and hemocompatibility. Because SrSiO3, SrF2, PZM and Ca3O5Si have the promising properties. This project's work packages are split into four categories based on the interdisciplinary approach since it involves the synthesis and characterization of PZM, the processing and characterization of cement, the identification of rheological parameters utilizing ISO standardizations, and hemocompatibility, and acquiring new transferrable skills. Additionally, the interactions among the selected compounds will be determined. The scientific impact of this project is comprehending the physical properties and the immune system's response to evaluate the cement's suitability as a replacement for existing materials, as well as resulting in further uses in dentistry and medicine. The societal impact is providing millions of patients in Europe with predictable and outstanding treatment outcomes each year to maintain pulp vitality and health. Eventually, it will ease the financial load on millions of patients who need dental care, will be avoiding inflated medical expenses and misuse of the patent (economic impact).

SrSiO3-based Dental Pulp Capping Cement

Per- og polyfluorerte stoffer (PFAS) er en stor gruppe menneskeskapte kjemikalier med høyt fluorinnhold som antas å ha negative helseeffekter. Kilder til PFAS kan være produksjon av vann-, varme- og flekkbestandige produkter og disse kjemikaliene er en del av hverdagen vår. PFAS påvirkning av biologiske systemer er ikke fullstendig forstått. Noen PFAS er antatt å øke risikoen for å utvikling av ikke-alkoholisk fettleversykdom (NAFLD) og øke risikoen for diabetes. 

For å forstå hvordan PFAS påvirker organene våre ønsker vi å bruke små laboratoriedyrkede organmodeller, kalt organoider. Disse miniatyrorganene kan dyrkes fra menneskelige stamceller og tilbyr et kontrollert miljø for å studere hvordan PFAS påvirker f.eks lever og bukspyttkjertelen vår, uten bruk av dyreforsøk.

For å studere helseeffekter må vi kunne måle nivået av biomolekyler som fettstoffer i leveren og hormoner i bukspyttkjertelen. Til dette trenger vi å utvikle analytiske verktøy for å måle effektene. Først vil vi bekrefte at når leverorganoidene eksponeres for enkelte PFAS-forbindelser utvikles det NAFLD-lignende sykdom ved å sammenligne den biokjemiske profilen (proteiner og metabolitter) til organoider av lever med PFAS-eksponerte organoider. Deretter vil vi utvide den analytiske verktøykassen for å undersøke hvilke metabolske veier som påvirkes, og om effekten er den samme i NAFLD-induserte og PFAS-eksponerte organoider. Vi vil også eksponere insulinproduserende bukspyttkjertelorganoider for PFAS for å undersøke effekten av PFAS på hormonproduksjon. Når effektene av PFAS-eksponering på lever- og bukspyttkjertel-organoider er etablert, vil organoidene bli samkultivert i en chip, og effektene av PFAS-eksponering vil bli undersøkt og sammenlignet med individuelle organoider.

Persistent organic pollutants (POPs) are believed to contribute to metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and type 1 diabetes. HE-POP aims to investigate the effects of per- and polyfluoroalkyl compounds (PFAS), a type of POPs), on organ function in a controlled environment.

Organoids are multicellular laboratory-grown miniature organs, that are grown from stem cells. HE-POP will use organoids to examine how PFAS affects our organs and develop cutting-edge bioanalytical tools and methodology to measure these effects using liquid chromatography-mass spectrometry. HE-POP hypothesizes that PFAS negatively affects organ function, as evidenced by changes in hormone and lipid levels characteristic of NAFLD and type 1 diabetes. 

Organoids offer a controlled environment to study the effects of PFAS on the liver and pancreas, without the use of animal models. HE-POP aims to gain evidence of the negative effects of PFAS on organ function through controlled experiments on organoids and aid in understanding the biological mechanisms underlying NAFLD and type 1 diabetes.

HE-POP has fundaments in UN sustainable development goals, specifically #3, #12, and #14/15, seeking an understanding of diseases with worldwide prevalence, and understanding how POPs affect our life and surroundings and help enable the right regulatory actions and replacement chemicals.

HE-POP: Studying the Health Effects of Persistent Organic Pollutants, Using Mass Spectrometry, Organoids, and Organ-On-A-Chip

Midlene fra IS-NAD-Samarbeid med NORAD-land fordelt på år

Midlene fra IS-NAD-Samarbeid med NORAD-land fordelt på fylker

Midlene fra IS-NAD-Samarbeid med NORAD-land fordelt på fagområde

Lege

El-Komy, Mohamed Egyptisk spes 2007

Our aim is to go into Phase 2 clinical trials and above of combined ATMPs focussing on:
- technologies ready to undergo interventional clinical trials in patients/end users assessing the usability and clinical performance, and/or
- technologies that have demonstrable safety/performance profiles and should undergo clinical validation in view of their inclusion into guidelines for specific clinical pathways.
- Delivery of safe and clinically validated combined ATMPs that are compliant with current European regulatory requirements. The related regulatory work should be considered as an essential component and the proposed work should involve consultation/interaction with competent regulatory agencies such as the European Medicines Agency (EMA) or national regulatory agency. Applicants are encouraged to seek regulatory and/or Health Technology Assessment (HTA) advice as appropriate.

We will include innovative treatments for any medical condition that are ready to be assessed for clinical efficacy (performance and clinical benefit) in a specific indication on a big number of patient cohorts; already existing market solutions are not in the scope of this topic.

PES-RIA: Clinical trials of combined Advanced Therapy Medicinal Products (ATMPs)

Antimikrobiell resistens (AMR) – bakteriers utvikling av resistens mot antibiotika, mirakelmedisinen de siste 100 årene – er en økende global trussel. De skyldige er mange, men resultatet er det samme: bakterier får styrker som overmanner antibiotikabehandlinger og gjør dem ineffektive og til og med ubrukelige. En studie fra 2019 fortelleross at 141 000 dødsfall i høyinntektsland var direkte knyttet til bakteriell AMR. To krefter driver frem spredningen av AMR. Den ene er svekkelsen av behandlinger gjennom utviklingen av patogener, fremskyndet av menneskelig atferd. Den andre er fraværet av farmakologisk innovasjon for å svare på en slik ny evolusjon. Det samlede resultatet er et innovasjonsøkosystem som ikke ligger i forkant av den utviklende faren. Her skal vi gjøre en forskjell. I prosjektet  vil vi presenteres en ny modell som kan undersøke nye teknologier som reduserer bruken av antibiotika ved fjerning av bakterier på infiserte implantater. Vår nye modell vil redusere bruken av forsøksdyr

The increasing use of biomaterials and medical devices has led to the emergence of new families of diseases related precisely to the use of these new technologies. Titanium dental implants are made with rough surfaces that facilitate good bone integration, but this approach also promotes bacterial adhesion and biofilm formation, and thus, infections. Preventive measures involve surface modifications of titanium implants, regenerative materials to counteract infection-induced bone loss, and debridement of implant surfaces. It is an intricate balance to find the right combination between the implant material, cleaning methods, and regeneration of bone loss. There is a high rate of colonisation of these surfaces due to the induction of biofilm-growing microorganisms, which are progressively resistant to antimicrobial therapies. The accumulation of microbes and biofilm formation, both in teeth and dental implants, triggers an inflammatory process characterized by the destruction of tooth/implant supporting bone. Unless biofilms are appropriately controlled, they accelerate their physiological heterogeneity and a series of complex interactions follows that results in chronic inflammation and loss of adjacent tissues. The condition thus often develops into a vicious circle with a great toll on the general health of the patients. The only way to break the cycle is through rigid biofilm control.  
MISFAITH aims to develop a dynamic multispecies biofilm model that can be used to model and test 3 novel methods for tackling the challenges associated with biomaterial-induced infections. Success in MISFAITH will have an enormous impact on the dental biomaterials field since as it would shift current treatment procedures to regenerative outcomes, resulting in better treatments and higher patient satisfaction, and less use of antibiotics. Therefore, if successful, the project outcomes will have an enormous social impact and potential for patient welfare.

Multispecies biofilm for investigate non-antibiotic therapies in dentistry (MISFAITH)

Behandling av skjelettdefekter er en stor samfunnskostnad, og med en økt andel eldre i
befolkningen øker behovet for behandling betraktelig. Det gir en stor etterspørsel for nye og bedre
medisinske produkter, helst gjennom minimalt invasive metoder for kortere sykehusopphold.
Samtidig begrenser det nye EU regelverket bruken av menneske- og dyrederiverte produkter, som
øker behovet for velfungerende, syntetiske biomaterialer.
Målet med dette prosjektet er å lage en hydrogel som kan injiseres direkte inn i defektområdet
for rask regenerasjon av skadet benvev. For å stimulere benvekst vil vi bruke et celle-vennlige
polymer blandet med inorganiske partikler og et bioaktivt biomolekyl.
Prosjektet er ledet av Material Biomimetic AS som står for biomateriale og kommersiell
ekspertise. Vi samarbeider med Politecnico di Milano som står for ekspertise på hydrogels og det
Odontologiske Institutt, Universitetet i Oslo som står for det kliniske perspektivet og in vitro testing
av produktkandidatene. PhD graden blir en dobbelgrad, der kandidanten vil forsvare sin avhandling
både i Milano og i Oslo

I perioden er det blitt forsket på ulike kombinasjoner av hydrogeler og alternativer til nuklearingsagent i hydrogelen. Det er fullført ein avansert in silico modellinger på hvordan dette systemet vil påvirke biomineralisering.

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.

Next generation hydrogel for bone tissue engineering

The main objective of this Eurostars project is to develop a new injectable hydrogel loaded with a bioactive peptide (NuPepTM) and an inorganic phase (e.g. Smartbone® microparticles) that can be injected directly into the bone defect site for a faster bone regeneration. Injectable scaffolds provide numerous advantages over pre-formed scaffolds (implanted through surgeries). The gel to be developed will target 2 medical applications: craniofacial/dental treatments and orthopaedic applications – namely spinal fusion. Each of these applications have specific challenges (e.g. at mechanical level) and it is expected that specific formulations for each application will be required in order to reach optimal regeneration. The new product rely on promising technologies, NuPep (innovative bioactive peptides) and Smartbone® (an osteoconductive and angioconductive bone substitute), that were developed and are being exploited by the members of the team that will form the Eurostars consortium. Such technologies have demonstrated huge potential to efficiently regenerate bone in a controlled process, avoiding side effects such as cancer development. We believe that the combination of these technologies in an injectable system will disrupt bone regeneration existing systems by inducing a controlled regeneration while being administered through minimal invasive procedures. The Eurostars project enable us to: 1) formulate the ideal combination of gel, peptides and inorganic phase to each envisaged application, 2) characterize the physical and biological properties of the final products; 3) obtain safety and performance data on in vitro + in vivo models, i.e. pre-clinical testing on craniofacial and spinal fusion bone regeneration. The Eurostars program will provide the necessary financial input to develop and validate our injectable system, which has a huge potential to positively disrupt current methods, positioning the system for clinical trials initiation.

OsteoPepGel

The ultimate goal in tissue engineering for wound healing is to produce a material that promotes complete and scar free regeneration of a functional outer barrier (e.g. mucosa or skin). In humans, mucosa and skin represents about one seventh of the body mass. Almost any trauma, infection or surgical procedure involve breaking this outer barrier and produce an ulcer. In healthy persons and under normal conditions, skin and mucosa rapidly regenerate and restore tissue integrity with complete epithelial coverage. Should however the situation be challenged by extensive trauma, burns, infections, chronic inflammation, metabolic disease or other pathologies the result are ulcers that heal very slowly or not at all, often with debilitating or even life-threatening consequences to the patient. Epithelial cell growth and migration are orchestrated by the underlaying dermis, a mesoderm derived, connective tissue, and regeneration of the mesodermal component is an absolute necessity for proper wound healing. Several strategies have been developed to restore dermal function. These include collagen membranes, decellularized dermis from donors or synthetic graft alternatives. So far, these approaches have been unreliable at best and auto-grafts and transplants (that both create their own problems with donor site morbidity, risk for disease transfer and infections and graft rejection) remain the only predictable method for treating hard-to-heal ulcers today. The major reasons for the failures of these approaches are most probably lack of physical strength combined with poor integration with the subjacent tissues and lack of biological signals that can home in precursor cells (e.g. stem cells and fibroblasts) from surrounding healthy tissues, and finally, the lack of biological signals for epidermis formation.

DermaG: next generation wound dressing

Corticalis AS has developed NuBone Gel - a novel and patented gel for the abolishment of oral biofilms that, in severe cases, induce bone degradation, tooth loss and dental implants failure. Our product’s biomimetic mode of action and its multiple effect, both antibacterial and abrasive to enable debridement, allows for an ultra-effective, safe and predictable biofilm removal. Corticalis will lead the project, which will focus on product maturation, preparation of the market launch and commercialization of our non-antibiotic-based product.
The main barriers for Corticalis going forward are related to prevailing technical and market-related challenges. This project will enable performing the final optimization on packaging, preparing a pilot production to supply testing activities and clinical studies to reach the CE certification, demonstrating the product to end-users (dentists, hygienists, dental surgeons and patients), and preparing the market launch in Europe and US.
The EIC Accelerator program provides a unique opportunity for Corticalis to showcase the potential of our innovation and gain market intelligence. The completion of the project objectives is important for ensuring a successful entrance to the market and commercialization of our innovative gel product.

New, ultra-efficient, non-antibiotic gel for clinical decontaminations of ailing bone anchored implants and teeth

Deterioration of building materials driven by fracture evolution and corrosion, imposes huge economic burdens to Europe. Corrosion alone accounts for worldwide expenditure over 1 trillion US dollars, amounting to 3-4 % of the GDP of devel-oped countries. NanoHeal will focus on the development of strategies for self-healing of cements used in the construction industry and in biocompatible implants. Inspired by biomineralization in nature, we propose that the interfacing of organic compounds with minerals will bring a new paradigm to design cementitious materials.
Healing in construction and biogenic materials can be achieved by controlled dissolution and growth at mineral interfaces under nanoconfinement. Building knowledge in this research area is therefore of utmost importance. Recent results show that organic molecules and membranes at mineral-fluid interfaces drastically modify nucleation and growth of the adjacent solid surfaces . Classical theories fail to predict these observations, highlighting the need for improved concepts, theories and models to design self-healing materials. 
Organic molecules are ubiquitous in limestone, chalk and biominerals. They are also used as admixtures in the cement industry. However, their role in construction materials is not well understood, while biomolecules are clearly of key im-portance in shaping biogenic minerals. We believe that learning the main lessons of how organic molecules interact with biogenic minerals will offer new routes to design stronger materials with the ability to heal themselves. This is the key scientific aim of NanoHeal, which will be achieved by combining unique experimental and computational modelling capa-bilities.

NanoHeal: Nano-tailoring organo-mineral self-healing materials

The RAPIDSCAF project relates to the TOPIC: Biological scaffolds for tissue regeneration and repair (RIA) (identifier: NMBP-21-2020), refer to the Call topic domain “Implementation of innovative manufacturing technologies (e.g. 3D printing) for affordable fabrication of patient-specific scaffolds planned in respect of the foregoing.”
Techniques of the fabrication of 3D scaffolds are subdivided into a conventional and rapid prototyping. Conventional techniques of scaffold fabrication include the construction of porous polymer structures, but it is difficult to obtain complex structures with tunable microscale and macroscale using these methods. Rapid prototyping is related to CAD/CAM techniques and 3D printing. These methods provide with much better resolution and precision, yet have numerous problems for application in real life.
One of the technologies of rapid prototyping suitable for scaffold production is photopolymerisation using ultra-short pulse lasers. This technology is superior in resolution, precision and versatility which may be achieved. More, it allows required macro to micro scale manufacturing, such as production of larger size scaffold with surface modification in micro/nano scale. Therefore it may enable not only better osteoblast attachment for bone mimicking scaffolds, but also provide required functional properties for stem cells or medical additives induction and at the same time enable true personalisation of the scaffold with reference to unique patient. Another important advantage of this technology is freedom of production (not regular 3D printing layer by layer) and possibility to merge different materials in one scaffold. Polymers themselves are good material for scaffolds because their chemical properties can be modified by introducing various chemical moieties that produce derivatives possessing enhanced adhesion, crosslinking, and biodegradability properties.

Fast universal production technology of multifunctional bio-scaffolds RAPIDSCAFF

The aim of the 3D printed active personalized implants (3D-API) is to develop next generation strategies for osteoarticular tissue engineering combining 3D printing, stem cell application and drug delivery. Our vision is to develop a composite implant mimicking natural osteoarticular healing. We aim to develop revolutionary in situ 3D printer enabling formation of scaffold absolutely tailored to the defect properties of each particular patient. In addition, the technology will improve the performance of healing due to the combination of 3D printing and drug delivery systems. The active behaviour of implant will be based on the regulated release of active molecules at exact time (temporal control of release) and space (spatial control of release) stimulating embedded cells. Performance of implants will be verified in a complete pre-clinical setup and the project will bring the technology to TRL5. The 3D-API consortium brings together multidisciplinary academic and private sector teams covering the entire range of competences required to develop these innovative new therapeutic approaches. A balance of academic and SME partners will ensure it has all the requisite skills in fundamental science and its translation to marketable products to bring the goals of this proposal to fruition. It includes companies involved in development of drug delivery systems (INCU), 3D bioprinting (Regemat3D), stem cell biology (Orthosera) and biomaterials for tissue engineering (Corticalis). The clinical applicability of the products will be ensured through the involvement of 3D printing (IBEC, BIONEER, SZECH, SOTON), polymer chemistry (KEM), drug delivery (HSRW), biological (stem cell biology – BIONEER, IEM, Donau University) and clinical experts (Donau University). The professional dissemination and project management will be guaranteed by EURICE (?). T

IS-NAD-Samarbeid med NORAD-land

El-Komy, Mohamed Egyptisk spes 2007

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IS-NAD-Samarbeid med NORAD-land

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