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HypOrth European research project relies on specialist collaboration
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Editor’s Note: This article by Christoph H. Lohmann, MD, PhD, and Aare Märtson, MD PhD, is the second in a series of articles in Orthopedics Today Europe about activities of the EFORT Basic Research Group.
Total joint arthroplasty is one of the most important procedures in musculoskeletal reconstructive surgery. Loosening, for various reasons, may be a major complication with impact on patients, health care providers and medical technology industries.
The European collaborative project HypOrth pursues two major goals: HypOrth intends to improve the understanding and diagnosis of complications associated with an implant, primarily focusing on adverse immune reaction and infection; and based on these insights, the project will develop innovative approaches for renewals in orthopaedic total joint arthroplasty (TJA) with improved biocompatibility and aims to develop hypoallergenic material for endoprostheses. The HypOrth project is built upon the cooperation of leading specialists, such as orthopaedic surgeons, immunologists, molecular biologists, modelers and data analysts, together with material scientists and a prosthesis manufacturer that will connect medical, scientific and technical areas. The consortium consists of eight partner organizations from seven European countries.
The project team is supported by a scientific advisory board, which includes five experts that represent the key aspects of activities of the project. This board shall not only ensure the highest standard of research and monitor the progress of the project by taking part in the annual meetings, but will also ensure the compliance with all necessary ethical regulations. Whenever appropriate, it will consult the consortium and make recommendations on how to best improve project performance.
Objectives
One of the main objectives of HypOrth is the investigation of immunological mechanisms of aseptic loosening of orthopaedic endoprostheses. In our previous work, we showed the appearance of diffuse and perivascular infiltrates of T- and B- lymphocytes and plasma cells, massive fibrin exudation and accumulation of macrophages. However, the mechanisms leading to these signs of adverse immune reaction are not yet understood based on a 2005 study by Willert and colleagues and on a 2013 study by Lohmann and colleagues.
A further objective is to identify cytokines, which are altered in patients with adverse immune reaction. We hypothesize there is a set of differentially expressed or regulated cytokine biomarkers that discriminate the immune response associated with the induction of allergic sensitization from non-allergic immune response and infection. Additionally, the results will be used for creation of a computational model for adverse immune reaction.
Patient samples will be collected at two large TJA centers. The cytokine levels will be compared between patient pools and groups. Evaluated data will be used for mathematical modeling of regulatory network of adverse immune reaction.
The computational model will be developed that allows us to predict the risk for an adverse immune reaction (AIR) based on genetic, immunological, and biomechanical patient and material data. To achieve a predictive computational model of AIR, the following steps will be taken:
identification of the relevant genes and cytokines from the patient data to establish a reasonable input vector HOPV (HypOrth patient data vector) for the model;
construction of a set of stochastic and structural equations to describe a model for the occurrence of an AIR based on the HOPV;
extension of the set of equations by incorporation of biomechanical data; and
implementation of two versions of the complete model: a preoperative and intraoperative vector modeling (cHOPV); and ideally, a predictive vector model only based on preoperative data (pHOPV).
Summary
The aims of HypOrth are the following:
- identification of AIRs to implant material and differentiation of AIR from low-grade infection in the context of prosthesis loosening; inclusion of epidemiological and clinical expertise and the finding of diagnostic biomarkers for AIR;
- understanding mechanisms of AIR and develop predictive computational models;
- finding of predictive biomarkers for application in personalized medicine;
- testing of conventional and new material combinations for implant and coating on different cell systems: bone cells and immune cells for biocompatibility, antibacterial properties and evoking immunological parameters, including the newly identified biomarkers; and
- evaluation of data and production of prototypic hypoallergenic implant.
The following are some recent publications from HypOrth in chronological order of publication:
- Metsna V, et al. Acta Orthop. 2014;doi:10.3109/17453674.2014.931198.
- Singh G, et al. Bone Joint J. 2015;doi:10.1302/0301-620X.97B7.35163.
- Drynda A, et al. J Biomed Mater Res A. 2015;doi:10.1002/jbm.a.35330.
- Chamaon K, et al. J Biomed Mater Res A. 2016;doi:10.1002/jbm.a.35549.
- Singh G, et al. Acta Orthop. 2016;doi:10.1080/17453674.2016.1188346.
- Drynda A, et al. J Biomed Mater Res B Appl Biomater. 2016;doi:10.1002/jbm.b.33770.
- Singh G, et al. Bone Joint J. 2016;doi:10.1302/0301-620X.98B8.36663.
- References:
- Lohmann CH, et al. J Bone Joint Surg Am. 2013;doi:10.2106/JBJS.L.01273.
- Willert HG, et al. J Bone Joint Surg Am. 2005;doi:10.2106/JBJS.A.02039pp.
Image: Lohmann CH
- For more information:
- Christoph H. Lohmann, MD, can be reached at Department of Orthopaedics, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany; email: christoph.lohmann@med.ovgu.de.
- Aare Märtson, MD, PhD, can be reached at Tartu University Hospital, Department/Clinic of Traumatology and Orthopaedics, Puusepa 8, Tartu 51014, Estonia; email: aare.martson@kliinikum.ee.
Disclosures: Lohmann reports he receives personal fees from Waldemar Link GmbH and Mathys Medical and grants from Foundation Endoprothetik and BMBF. Märtson reports royalties from W. Link (Link Academy) for providing education programs, receives royalties for lectures and grants for travel from DePuy Synthes.