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Preclinical research

OSapp expansion continues

In 2021, the virtual osteosynthesis software tool and interactive online learning platform, OSapp, expanded the range of virtual biomechanical models that it features and established several internal AO collaborations. OSapp meets a real need among surgeons in training and their mentors for support in learning, exploring, and understanding biomechanical principles of implant fixations and bone healing.

Free to use, it includes guided and unsupervised learning experiences that offer an interactive, visual way of understanding the biomechanical principles behind multiple basic fixation concepts, based on Stephan Perren's strain theory. It can be integrated further into AO educational offerings—especially those with a hybrid component, as AO President Florian Gebhard explained on AO TV during the AO Davos Courses 2021.

OSapp is being developed to integrate with other AO platforms such as AO Milestones, where it will be incorporated through the fundamentals module. Pilot projects hyperlinking with the AO Surgery Reference (for the cortical lag screw module) and supplementing the AO Skills Lab (for the station on plate mechanics) have demonstrated OSapp's potential to enhance the impact and value of existing AO educational offerings.

Officially launched at the AO Davos Courses 2020, OSapp sparked intense worldwide interest online, was showcased at the German Congress of Orthopaedics and Traumatology (DKOU) 2021, and had a dedicated booth at the AO Davos Courses 2021. OSapp is developed at the AO Research Institute Davos (ARI) with resources from the Strategy Fund within the AO Innovation Translation Center (AO ITC).

ARI strengthens cooperation with BBCE

International cooperation between institutes and universities plays an essential role in scientific research. At the AO, research is by its very nature both cross-border and interdisciplinary. The AO Research Institute Davos (ARI) in 2021 continued to strengthen its research cooperation with the Baltic Biomaterials Centre of Excellence (BBCE), with which it is working to establish a joint center for advanced biomaterials development in Latvia.

Working with the BBCE gives ARI the opportunity to contribute to the establishment of a biomaterials center of excellence in Europe. Founded on a principle of sharing best practices in research, the BBCE's primary objective is to build research capacity in the Baltic area.

The project has a wide variety of subject-specific topics, such as biomaterials research, drug delivery, and 3D biomaterials printing, and includes general research-relevant areas such as lab management, quality control systems, intellectual property (IP) management, and knowledge transfer.

Due to the COVID-19 pandemic in 2020 and for much of 2021, this joint work was carried out online.

In August 2021 the first visit was possible: ARI hosted five students and two supervisors, who were the winners of the BBCE BIO-GO-HIGHER Latvian High School National Science Competition. They were awarded the opportunity to travel to Davos and participate in ARI laboratory activities for three days.

An additional two visits took place in November and December when members from the different BBCE Riga Institutes shared expertise in biomaterials research excellence and best practices in research more broadly.

Longer planned visits, of three to six months, by students and postdocs from Latvia coming to work alongside ARI researchers were also finally possible. These visits are at the core of this cooperation and are an opportunity for both partners to learn from each other in laboratory settings and discussion groups.

While ARI is at the heart of this joint work, the Development Incubator and the AO's Clinical Evidence unit under the AO ITC also gave lectures to BBCE participants. Health-care professionals from Riga also attended the AO Davos Courses last year.

Find out more about the latest visit as part of this initiative here.

SPF sheep facility delivers lasting investment in research excellence

In 2021, ARI's preclinical research facility opened the doors to its highly anticipated specific-pathogen-free (SPF) sheep facility, directly adjacent to the AO center in Davos. This state-of-the-art, 6,575-square-meter zone expansion houses the first SPF sheep flock outside North America.

It is a particular achievement that this vital contribution to the city's position as a leading global research and innovation hub was completed during such challenging times. An investment on this scale demonstrates the AO's commitment to the highest animal welfare standards in research, and patient-outcome-focused R&D.

The facility also has a built-in biogas project to reduce methane output and produce renewable green energy and heat.

Research with impact

Six scientists from ARI rank among the most-cited researchers in the world across all scientific fields, according to researchers at Stanford University.

Research quality can be difficult to assess, but this ranking demonstrates that ARI research is high quality and high impact. This means that ARI research kick-starts lines of inquiry later picked up by researchers elsewhere and makes ARI a prime choice for inclusion in consortia that achieve successful applications for grant-based funding.

In October 2021, Stanford published a database of over 100,000 of the most-cited authors from around the world in all scientific fields in 2020, based on Scopus citation metrics. ARI Director Professor Geoff Richards, Vice Director Professor Mauro Alini, ARI Program Leader Regenerative Orthopaedics Professor Martin Stoddart, Deputy Program Leader Regenerative Orthopedics Dr Sibylle Grad, Focus Area Leader Infection Biology Dr Fintan Moriarty, and Focus Area Leader Polymers and Surfaces Dr David Eglin, were all recognized.

One example of this research excellence is the publication in Nature Reviews Disease Primers on nonunion bone fractures, which achieved an impact factor of 53, well above the usual range for orthopedic research publications which is around 2.5 or 3. These rankings indicate that ARI is able to achieve clinically relevant results while also attaining globally recognized academic excellence.

Explore a selection of ARI's notable research published in 2021

Bone infection: a clinical priority for clinicians, scientists and educators

Eur Cell Mater. 2021 Oct 18;42:312-333.

Moriarty TF, Muthukrishnan G, Daiss J L, et al.

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The influence of biomechanical stability on bone healing and fracture-related infection: the legacy of Stephan Perren

Injury. 2021 Jan;52(1):43-52. doi: 10.1016/j.injury.2020.06.044. Epub 2020 Jun 26.

Foster AL, Moriarty TF, Zalavras C, et al.

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Butyrate Inhibits Osteoclast Activity In Vitro and Regulates Systemic Inflammation and Bone Healing in a Murine Osteotomy Model Compared to Antibiotic-Treated Mice

Alexandra Wallimann, Walker Magrath, Brenna Pugliese, et al

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Biomechanical analysis of recently released cephalomedullary nails for trochanteric femoral fracture fixation in a human cadaveric model

Arch Orthop Trauma Surg. 2021 Nov 8.

Torsten Pastor, Ivan Zderic, Dominic Gehweiler, et al.

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Angular stable locking in a novel intramedullary nail improves construct stability in a distal tibia fracture model

Injury accepted 2 November 2021, Available online 6 November 2021

Ivan Zderic, Boyko Gueorguiev, Michael Blauth, et al

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Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via SOX9 and PPARG, but Not RUNX2

Int J Mol Sci. 2021 Apr 30;22(9):4785. doi: 10.3390/ijms22094785.

Della Bella E, Buetti-Dinh A, Licandro G, et al.

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Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis

Stem Cell Res Ther. 2021 Jan 7;12(1):11. doi: 10.1186/s13287-020-02062-2. PMID: 33413584

Wangler S, Kamali A, Wapp C et al

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A Hyaluronic Acid Hydrogel Loaded with Gentamicin and Vancomycin Successfully Eradicates Chronic Methicillin-Resistant Staphylococcus aureus Orthopedic Infection in a Sheep Model

Antimicrob Agents Chemother. 2021 Mar 18;65(4):e01840-20 doi: 10.1128/AAC.01840-20. Print 2021 Mar 18.

Willemijn Boot, Tanja Schmid, Matteo D'Este et al

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The waves that make the pattern: a review on acoustic manipulation in biomedical research alternatives

Nat Rev Dis Primers. 2021 Aug 5;7(1):57. doi: 10.1038/s41572-021-00289-8.

Wildemann B, Ignatius A, Leung F, et al

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Bacteriophage Therapy for the Prevention and Treatment of Fracture-Related Infection Caused by Staphylococcus aureus: a Preclinical Study

Microbiol Spectr . 2021 Dec 22;9(3):e0173621. doi: 10.1128/spectrum.01736-21. Epub 2021 Dec 15.

Jolien Onsea, Virginia Post, Tim Buchholz, et al

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