Musculoskeletal Tissue Regeneration

ESR project

3.6

Title of project

Inflammation as a tool for regenerative bone formation (iBone)

We offered

A 4-year PhD student position in the field of applied regenerative bone research, coordinated from the orthopedic department in Utrecht. The project will focus on preclinical animal studies to take the concept of inflammation induced bone formationto the next level .

Department

The Department of Orthopaedics UMC Utrecht

Description

Failure of the natural bone healing mechanism occurs in 10% of trauma and orthopedic surgeries. This necessitates additional bone reconstruction techniques to boost the healing response. The most applied strategy is to transplant patient’ own bone, however this technique has serious drawbacks in terms of costs, safety and efficacy. A broad range of bone graft substitutes has been developed during the past fifty years, but no satisfactory solution has been accomplished.

We investigated the feasibility of instigating bone regeneration with a controlled inflammatory response. The basis for this novel idea was the clinical observation that certain infectious conditions lead to huge amounts of new bone formation. In rabbit models, we followed a systematic approach to characterize and recreate the conditions that lead to new bone during infections. New bone formation was found when inactivated bacteria were applied with different techniques or with different archetypical bacterial strains. Taking this ‘top-down’ method further, we identified specific bacterial antigens and cytokines that are involved in inflammation-based bone stimulation. This is the basis of a patent application held by the UMC Utrecht.

Our discovery that immunomodulatory factors can be used as adjuvants to enhance bone grafts, initiated a joint effort with Kuros BV to improve their latest generation ceramic bone substitutes. Large comparative studies will be performed to identify natural antigens with optimal bone-inductive properties. To facilitate regulatory approval of the end product, artificial antigens and recombinant cytokines will also be evaluated that have already been tested in patients. Of these, pro-inflammatory synthetics are most easily harnessed for bone regeneration purposes. In this project we aim to first optimize the coating method to maximize its immunogenic and bone-inductive properties. In a final stage, the subset of novel and promising deliverables will be tested in direct comparison to the gold standard of autologous bone in a large preclinical bone healing model.

You will be part of a team of researchers with specific knowledge of orthopedic surgery, bone regeneration, and osteo-immunology. The project involves the development of optimal coating strategies for the pro- inflammatory agents on ceramic scaffolds. In the final stage, the most promising deliverables will be tested in direct comparison to the gold standard of autologous bone in a large preclinical bone healing model

Contact person & more information

Dr. J. Alblas, UMC Utrecht
J.Alblas@umcutrecht.nl

RESCUE

This project is part of RESCUE, a multidisciplinary, intersectoral and interdisciplinary PhD training programme in Regenerative Medicine and Stem Cells organised by UMC Utrecht (coordinator) and Utrecht University. RESCUE is partly funded by the European Commission under Horizon 2020's Marie Skłodowska-Curie Actions COFUND scheme. There are specific requirements with regards to English language and mobility for candidates who would like to take part in this programme. More information