ARI Projects

All ARI projects are Applied Preclinical Research or Applied Preclinical Development projects focused towards clinical applications.

Definitions (within the applied research):

  1. Exploratory Applied Preclinical Research is fundamental research, to solve major clinical problems over a extended timeframe (over 10 years)
  2. Translational Applied Preclinical research aims at developing a clinical applicable result in around 5 years and builds upon the fundamental applied preclinical research. This research is usually not possible without the previous fundamental applied preclinical research.

AOCMF​ 

Surface modification of PEEK to improve tissue integration to devices such as CMF patient specific implants

Problem
Osseointegration to PEEK devices such as CMF patient specific implants has been found to be limited, due to PEEK's inherent low surface energy and can therefore cause implant loosening as a result of fibrous encapsulation.

Goal
Investigation of plasma surface modification of PEEK to increase surface energy and the resulting effect on cell attachment and function, comparing to cpTi as the gold standard.​

AOCMF CPP​Back to Top

Evaluation of accuracy of CAD/CAM fabricated splints for orthognathic surgery

Problem
The clinical outcome in orthognathic surgery depends critically on accurate preoperative planning. The need for three-dimensional preoperative assessment has been documented over the past years and conventional planning has been added by a three-dimensional computerized approach. Computer-assisted virtual planning could on one hand replace existing conventional planning and model surgery and would on the other hand improve the accuracy of the clinical outcome. In conventional as well as in virtual approaches, surgical splints are usually used for transferring the surgical plan to the patient. Conventional splints are manufactured on the plaster cast models; whereas in computerized approaches this is achieved using CAD/ CAM (Computer-aided design/ Computer-aided manufacturing) techniques (i.e. manufactured Rapid Prototyping techniques). However, there is still controversy concerning the best approach to manufacturing of accurate CAD/ CAM splints.

Goal
To define a suitable workflow to produce Rapid Prototyping splints used for orthognathic surgery. To obtain an accurate virtual model of the dental surfaces, different radiological and surface scan modalities will be assessed. The best manufacturing process will be integrated into computerized planning procedures of given clinical cases.

Workflow for custom-made CAD/CAM titanium plates based on virtually planned maxillofacial reconstruction

Problem
The reconstruction of maxillofacial defects using prefabricated vascularized fibular grafts is still a technical demanding and time consuming procedure. Computer-Aided Surgery (CAS) techniques could significantly contribute to improve its preoperative assessment and planning and its intraoperative execution, thus resulting in better overall surgical outcome.

Goal
The goal of the study is to improve maxillofacial defect reconstruction by the definition and execution of an expert driven surgical CAS workflow, which will be tested in this project in a model surgery patient.​

​​AOSpineBack to Top

Surface modification of PEEK to improve tissue integration to devices such as CMF patient specific implants

Problem
Osseointegration to PEEK devices such as spine cages has been found to be limited, due to PEEK's inherent low surface energy and can therefore cause implant loosening as a result of fibrous encapsulation.

Goal
Investigation of plasma surface modification of PEEK to increase surface energy and the resulting effect on cell attachment and function, comparing to cpTi as the gold standard.

The effect of surface modification of PEEK on bacterial adhesion

Problem
The infection rate associated with devices composed of PEEK is not available from the literature, this makes the risk of infection difficult to manage. In addition the effect of changing the surface chemistry of PEEK on bacterial adhesion and the resulting infection rates are also not known.

Goal
To evaluate and compare the effect of different plasma surface modifications of machined and injection moulded PEEK on in vitro bacterial adhesion and biofilm formation.

Comparison of the osseous integration of two different materials used for ventral spondylodesis of the lumbar spine

Problem
Autogenous and xenogenous bone grafts are often used in spondylodesis. The healing is not always a success.

Goal
Histological, morphological and radiological investigations on autogenous and xenogenous bone grafts. The graft itself was evaluated for fractures and osteolysis to prove a correlation between the disc and graft area.

Irrigation procedures for increased patient safety in vertebroplasty

Problem
Risk factors in vertebroplasty are fat embolisms and cement leakage. With rising acceptance of prophylactic augmentation of adjacent vertebrae in the osteoporotic spine, these risks will only increase.

Goal
Lavage prior to cement injection carries potential to reduce fat embolisms, injection forces and cement extravazation. The goal of the project is to develop an irrigation system for fat removal which can be embedded into the established clinical vertebroplasty procedure.

​​AOTrauma AOTECBack to Top

Ostesynthesis SKILL training technology

Problem
Human society these days is widely 'IT-centered' with cell-phones, video-games, the Internet. All these media ask for skills that were not necessary a decade ago. On the other hand, mechanical manual skills rapidly decline within the young computer fixated generation.

Goal
Learning modules need to be created and developed with which the (medical) students learn the basic hands on skills of (bio)mechanics and material properties. Also basic knowledge about how certain tools are properly used and maintained (drill bits, chisels, machines etc.) needs to be communicated to the new IT centered generation.

Osteosynthesis training kit

Problem
In AO-courses, participants learn to use tools and implants and to apply them properly. These courses need a huge organization, are not for free and make the participants travel to certain places.

Goal
Some aspects of teaching and learning in osteosynthesis are better done 'on-site', with inexpensive hardware and without a time consuming setup. A kit, made of simplified bone, implant and soft-tissue elements to teach, assess and understand the fundamental elements of osteosynthesis could help to solve the task.

AOTrauma AOTRCBack to Top

The effect of surface topography on stainless steel external fixator pins

Problem
The incidence of infection after external fixation with Electropolished Stainless Steel pins is high. The smooth surface of the EPSS pins may not allow maximal tissue integration allowing bacteria to easily colonise the pin tract. The topography of EPSS ex-fix pins may not be optimal to allow integration.

Goal
To determine the influence of stainless steel external fixation pins surface topography on tissue response and infection prevention.

​Development of a non-invasive imaging probe to identify bacteria

Problem
The diagnosis of infection surrounding an orthopedic implant has significant consequences, however, diagnosis of infection is not always easy and current diagnostic methodologies do not distinguish infection from inflammation in most cases.

Goal
To develop pre-op diagnostic tool to identify bacteria and distinguish from inflammation.

The Immune Response to Bacterial Contamination of Orthopaedic Implant Materials

Problem
The presence of any implant compromises local host immune responses and decreases inoculum required for infection by up to 100'00 fold. However, it is unclear as to whether different implant materials have different influence on this risk.

Goal
Identify the role of material choice in the immune response to infection for the most commonly used orthopaedic implant materials.​

Development of preclinical models of infection after osteosynthesis

Problem
A wide range of preclinical models of infection are available, however few have focused on the problem of infection after osteosynthesis.

Goal
Establish and validate both small and large preclinical models of implant related osteomyelitis after osteosynthesis.

Comparison of the clinical features, bacterial genotypes and outcomes of patients with implant related osteomyelitis due to Staphylococcus aureus and Staphylococcus epidermidis

Problem
Numerous bacterial virulence factors have been associated with disease severity for numerous infectious diseases, however, this has not been determined for infections after osteosynthesis.

Goal
Establish a collection of clinical bacterial isolates and follow up patient data to identify the bacterial virulence characteristics associated with implant related osteomyelitis.​

Cement augmentation methods for improved fracture fixation in osteoporotic bone

Problem
Osteoporosis challenges osteosynthetic fracture treatment. Post-operative failure of the fixation is frequently seen at various anatomical regions. Improved implant purchase is required to reduce the failure risk in order to allow for early and confident mobilization of the elderly patient.

Goal
Enforcement of the fixation with injectable biomaterials like bone-cements carries potential to significantly enhance the implant anchorage. New cement augmentation concepts are developed and evaluated with strong regard to the clinical application.

Artificial Retaining Telecasting

Problem
Natures' concept to heal a fracture is perfect with regards to stabilization and 'rebuilding' but not with respect to the time line introduced.

Goal
A technology is required, which helps nature to undertake the task quicker. Mechanical stabilization needs to be introduced as early as possible, as it is the case with the implants used today.

Prophylactic reinforcement of the proximal femur to prevent secondary hip fractures

Problem
Hip fractures represent a major health concern. The incidence will only increase with the aging of the population. The risk for fracturing of the contra-lateral hip increases after a first hip fracture had occurred.

Goal
To develop and evaluate concepts for prophylactic stabilization of the unfractured femur in order to avoid secondary trauma in osteoporotic bone.

Intra-operative assessment of bone quality

Problem
Bone quality is known as important indicator determining the biomechanical stability after fracture fixation. Particularly in osteoporotic bone, failure of the osteosynthesis occurs frequently.

Goal
Intra-operative measurement of the bone quality carries potential to markedly support the decision making process regarding choice of fixation hardware or operational technique in order to optimize the fracture fixation. The goal is to develop and evaluate a concept to locally analyse the mechanical competence of trabecular bone structures for prediction of the implant purchase.​

A novel approach for simplified computer aided surgery, exemplified on navigated guide wire placement for proximal femur fractures

Problem
Current solutions for computer aided surgery lack of wider acceptance due to considerable disadvantages regarding complexity, costs and effectiveness.

Goal
A simplified Computer Aided Surgery system shall be developed utilizing a conventional C-arm as imaging and navigation means rendering additional tracking and imaging equipment unnecessary. The concept aims to improve surgical routine tasks and shall be exemplified on advanced guide-wire placement for enhanced fixation of osteoporotic hip fractures.

Development of a dynamizable internal fixator system for large animal bone research with biofeedback technology

Problem
Various attempts have been made to mechanically stimulate the fracture to take advantage of fostered bone formation. However, the phenomenon is not fully understood and requires further investigation. For both, research and clinical application, biofeedback systems characterizing the healing process are gaining importance, but feasible solutions are still missing.

Goal
The goal of the project is to further develop and extend the portfolio of a recently introduced plating concept to serve as an advanced implant system for bone research using large animal models by stimulating and monitoring of the healing process.​

Biomedical Services for trauma network - Cancellous bone compaction

Problem
Cancellous bone compaction surrounding a blade implant is believed to enhance the implant anchorage. Up to date this was never proven.

Goal
To investigate the potential of compacted spongy bone to improve the cut-out resistance in DHS-Blade application.

Human Morphology Services

Problem
Many projects rely on medical image data (CT, MRI). Acquisition and preprocessing of such data is expensive and time consuming. With respect to ethical and economical reasons it makes sense to reuse data and know-how in different projects, mainly within the AO network.

Goal
Sustainable umbrella project for collecting medical image data and know how in image processing and analysis for efficient use in related projects. Within R&D projects and fellowships we offer services/support in:

  • medical image processing and analysis
  • 3D statistical bone shape analysis (e.g. used for optimized implant design)
  • database of CT-scans and 3D bone models
  • computed preoperative planning
  • medical rapid prototyping ​

Analysis of an infraacetabular screw corridor (Subproject of Human Morphology Services)

Problem
Acetabular surgery is one of the most challenging complex surgeries performed in orthopedic trauma. This includes the complexity of the surgical approach, the risk of neurovascular injury, and the three dimensional challenge of reducing and fixing the fracture itself. Achieving the goal of perfect fragment reduction and rigid fixation is difficult and furthermore, early joint movement should be allowed to avoid further postoperative complications (e.g. joint stiffness, muscle hypotrophy, thrombosis and pneumonia).

Goal
To analyze if there is a sufficient secure path to place an infraacetabular screw in most human pelvises. If generally applicable an optimal entry point of the screw related to the pelvic brim, the symphysis and other anatomic landmarks can be determined. Optimal angles of a drill or guide wire in the screw path should be calculated. The best position of an X-ray image intensifier in at least 2 or 3 different planes is to be determined, so that an adequate placement of the screw can be verified.​

Simplified approach for distal interlocking

Problem
Difficulty of nail interlocking resulting in high X-ray exposure and surgery time.

Goal
Development of a novel approach to ease the interlocking of intramedullary nails using an image intensifier and a custom made software algorithm, thereby reducing X-ray exposure and procedure time.

In vitro investigation of species and source dependent responses of osteoblast cells to internal fixation materials

Problem
While human cells are the ideal cell culture model for biomaterial studies issues regarding supply and donor variability are obstacles in their routine implementation. Other sources such as immortalized cell lines and primary non-human cells are considered attractive alternative cell culture models. However, variation in the source and species of the cells makes extrapolation difficult. Currently, very few studies have attempted to investigate species dependent and source dependent response of osteoblast cell culture models to clinically available implant materials.

Goal
In vitro investigation of species and source dependent responses of osteoblast cells to internal fixation materials to identify most/least applicable model for cell-material interaction studies.​

The effect of surface topography on stainless steel external fixator pins

Problem
The incidence of infection after external fixation with Electropolished Stainless Steel pins is high. The smooth surface of the EPSS pins may not allow maximal tissue integration allowing bacteria to easily colonise the pin tract. The topography of EPSS ex-fix pins may not be optimal to allow integration.

Goal
To determine the influence of stainless steel external fixation pins surface topography on tissue response and infection prevention

Development of a non-invasive imaging probe to identify bacteria

Problem
The diagnosis of infection surrounding an orthopedic implant has significant consequences, however, diagnosis of infection is not always easy and current diagnostic methodologies do not distinguish infection from inflammation in most cases.

Goal
To develop pre-op diagnostic tool to identify bacteria and distinguish from inflammation.

The Osteogenic Potential of Reamer Irrigator Aspirator Harvested Material and the Fate of the Reamed Bone

Problem
Osteogenic potential of the RIA harvested material is not yet completely characterized. Ways to boost this oteogenic potential have not been scientifically investigated.

Goal
To assess the osteogenic potential of RIA harvested material in vitro, and to assess ways to boost this osteogenic potential. Fate of the harvested site will also be investigated 3 months post-operatively.

Paravertebral venous PMMA leakage after vertebroplasty does not necessarily cause endothelial cell layer necrosis

Problem
During vertebroplasty, which is frequently used as a therapy in traumatic spine injuries, injection of PMMA can leak out and cause damage to the surrounding areas.

Goal
To investigate the distribution of PMMA leakage during vertebroplasty, and the soft tissue reaction next to it. This project also serves as "project scouting" because we document with one case report that we are capable to embed and investigate PMMA cement in cancellous bone.

Characterization of fibrocartilage differentiation at the attachment sites of the coracoclavicular ligaments. A study on human cadaveric tissue

Problem
The coracoclavicular ligament complex is considered as the prime restraint support of the acromioclavicular joint against superior and posterior translation of the distal clavicle with respect to the scapula. Despite the clinical importance of the coracoclavicular ligament complex, its structure and molecular composition have not been comprehensively studied.

Goal
To analyse the immunohistochemical labeled patterns of the extracellular matrix of the coracoclavicular ligaments in order to relate the molecular composition of the attachment sites to their mechanical environment. Ligaments were exposed from twelve fresh-frozen human cadaveric samples. Cryosections of methanol-fixed, decalcified tissue were made and the sections then labeled with a panel of monoclonal antibodies directed against collagens, proteoglycans and proteins of vascular components.​

Synthesis of a biodegradable scaffold to improve the integration in osteochondral defects and critical size defects in bone

Problem
The functional integration of engineered osteochondral implants into cartilage and bone tissues is still a major challenge. It is hypothesized that the implantation of a scaffold with well-defined structure (e.g. regional organization) and properties could improve the integration and healing of osteochondral defects. Similarly, the regeneration of the annulus fibrosus (AF) is challenging because of the tissue complexity, its mechanical and structural anisotropic properties and the actual limited knowledge about AF cell biology.

Goal
To create a construct for osteochondral defect repair with specialized bone and cartilage regions. To create an AF patch with mechanical and structural properties suitable for sealing of the nucleus pulposus and allowing AF repair via a cell therapy approach.

​Use of a Reamer Irrigator Aspirator​ device for autograft harvesting for the treatment of critical sized bone defects

Problem
Can Reamer Irrigator Aspirator (RIA)​ harvested material (boosted or non-boosted) be used to treat large bone defects?

Goal
To assess RIA harvested material (boosted and non-boosted) in the treatment of critical size bone defect models in the iliac crest (phase 1) and tibia (phase 2)

Effect of arginine deficiency on development of avascular non-unions

Problem
Treatment of non-unions

Goal
To investigate the role of NO Synthase on non-union development using a knock-out model.

Repair of osseous defects by resorbable implants in a knee model

Problem
Bone substitute behavior in cancellous bone is not fully understood.

Goal
To histologically assess the behavior of bone substitute in a cancellous drill hole model.

AOVetBack to Top

Development of an external fixator for large animals (calves)

Problem
The current transfixation pin cast system can be associated with severe pin loosening in calves

Goal
To develop using finite element analysis a new transfixation pin cast system and to biomechanically test the strain at the pin/bone interface.

Metallurgical evaluation of the TPLO plate in dogs with malignant tumors compared to healthy animals

Problem
Stainless steel cast TPLO plates may lead to sarcomas in dogs.

Goal
Histological, morphological and chemical investigations of different plates and tissue reactions in collaboration with EMPA to assess if there is a correlation between TPLO implants and tissue reaction.​

AOERBBack to Top

Ex Vivo and In Vitro Culture Models of Human Osteblast-Like Cells and the Effects of TGFbeta3 and Serum-Free Culture

Problem
Many features of the complex bone tissue are missing in 2D cell culture. A 3D tissue such as bone is characterized by interactions between different cell types with each other and the extracellular matrix. Therefore, we believe the effects of growth factors such as TGFbeta3 need to be investigated in a 3D situation prior to animal studies.

Goal
3D in vitro and ex vivo culture models of human osteoblast-like cells and effects of serum free culture and TGFbeta3.

Investigation of the in vitro differentiation potential of mesenchymal stem cells (MSC) in response to the surface microtopography of implant materials

Problem
Despite many studies showing the effect of surface properties on osteoblast behaviour pertaining to osseointegration, very little information has been accrued regarding a materials influence on innate stem cell differentiation and functionality. This is an important aspect of the cell-material interface given that mesenchymal stem cells are one of the first cells to contact an device upon implantation and therefore govern subsequent tissue responses.

Goal
Assess the innate ability of surface microtopography and material type to modulate mesenchymal stem cell differentiation.

Research Implant System

Goal
Establish a "golden Standard" with standardized implant systems for experimental studies of fracture healing with exactly defined, reproducible mechanical conditions.

  • Definition of the Microsite Layout for the website.
  • Definition of measuring parameters to validate the goal "golden standard in research studies"

Nucleus pulposus and annulus fibrosus cells: Cellular phenotype characterization and in vitro differentiation from mesenchymal stem cells

Problem

  • The molecular characteristics of intervertebral disc (IVD) cells, namely nucleus pulposus (NP) and annulus fibrosus cells, are still not adequately defined.
  • In spite of evidence for mesenchymal stem cell (MSC) differentiation towards IVD cells, the optimal differentiation conditions are not known.
  • Knowledge about molecular pathways leading to disc degeneration is limited so far.

Goal

  • To identify molecular markers that may characterize IVD cells and distinguish those from cartilage cells.
  • To identify in vitro culture conditions for differentiating MSCs towards the expression of this "disc-like" phenotype.
  • To develop a large molecular/proteins data bank on degenerative changes of IVD.

Survival and Differentiation of Bone Marrow Derived Mesenchymal Stem Cells into Disc Cells when Injected into an Intervertebral Disc Organ Culture

Problem
The impact of load and nutrition on intervertebral disc (IVD) regeneration by using mesenchymal stem cell is not known at the tissue level, i.e. on whole IVDs cultured in vitro.

Goal
To investigate how MSC will survive and differentiate into disc cells on IVD in a whole organ culture system.​

Endothelialized grafts for bone critical size defects treatment

Problem
Bone formation highly depends on osteogenic cells at the implant sites, but vascularisation is also crucial. The use of endothelial progenitor cells (EPC) together with bone marrow stromal cells (BMSC) seems a promising approach for successful cell grafting of critical-sized bone defects. One of the major problems preventing the clinical application is the time needed to expand the isolated EPC to the required numbers.

Goal
To isolate and characterize EPC from BMSC and peripheral blood.​

Biological approach for treating large bone defect

Problem
Critical size bone defects, being more than 1.5 times larger than the bone diameter, do not heal if left untreated. This constitutes a major challenge for trauma surgeons. There has been little recent progress towards the development of improved, clinically useful products.

Goal
To heal a critical size defect in a preclinical model via a biological approach (polymer scaffold with autologous cells and platelet rich plasma)

Identification and selection of osteogenic, chondrogenic and angiogenic cells from a heterogeneous population of mesenchymal stem cells

Problem
Identification of phenotypically homogeneous cells from a mixed population of stem cells is currently not possible.

Goal
The construction of a virus which is able to distinguish between the osteogenic and chondrogenic cells depending on the fluorescent color generated by the different cells.​

The effect of mechanical stimulation and biological factors on human mesenchymal stem cell chondrogenesis and hypertrophy

Problem
Methods for stable differentiation of human mesenchymal stem cells (MSCs) into resting chondrocytes for tissue engineering are not available.

Goal
To investigate the effects of mechanical load in combination with biological factors on the osteochondral differentiation of human MSCs.​

Ex-vivo culture of Bone Marrow Stromal Cells in a new bioreactor, to study the stem cell niche

Problem
The natural mesenchymal stem cell niche is still largely unknown.

Goal
Investigation of the stem cell niche using a bioreactor system. The aim of the project is to build a new bioreactor system which is able to maintain the culture of fresh and active bone marrow. Cells will then naturally attach to the enclosed polyurethane scaffold with the aim that an in vivo like niche is recreated. This would enable numerous studies to be investigated in the long term such as stem cell homing and maintenance of multipotency.

Thermoresponsive hydrogels based on natural polysaccharide

Problem
The most common approach to stable polysaccharide hydrogels is to chemically crosslink the linear polysaccharide to avoid rapid degradation and clearance from the implant site of unmodified polysaccharide. However, there are still technical drawbacks to overcome notably to engineer and ensure that the hydrogel can be injected and jellified in the desired biological tissue site. In addition, biological entities, such as cells and active agents, encapsulated in these solutions are usually exposed during crosslinking to reactive toxic moieties, such as free radicals and highly reactive chemical groups.

Goal
To develop thermoresponsive injectable hydrogels based on natural polysaccharide​

​​Extramural FundedBack to Top

AORF: Evaluation of a multi-modality image computing concept for the conduction of a prospective clinical multicenter study (AORF F-09-1H)

Problem
In Graves' ophthalmopathy, the orbital manifestation of Graves' Disease, the degree of exophthalmos reduction is difficult to predict, showing large variable operative results with existing surgical strategies; i.e. the degree of postoperative ocular globe retrusion may be too much or too little, and this is associated with functional and aesthetic problems. From the literature and clinical experience there are hints that the individual orbital anatomy may affect the degree of exophthamos reduction.

Goal
Development of individualized anatomy based surgical strategies for decompression surgery/orbital enlargement in Graves' Ophthalmopathy patients.

Study 1 in CT data of unaffected orbits (finished):

  1. Define morphological orbital parameters relevant for the choice of the surgical technique.
  2. Creation of orbital reference data in CT.

Study 2 performed in 10 Graves' Ophthalmopathy (ongoing):

  1. Technical feasibility study of image fusion of preoperative CT data and postoperative MRI data.
  2. Elaboration of a working sheet for a prospective clinical multicenter study.

Study 3. Prospective clinical multicenter study (if applicable).

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