Poster Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

Modulating innate immune responses to biomaterial-induced inflammation (#177)

Susan N Christo 1 2 , Kerrilyn R Diener 1 2 3 , Akash Bachhuka 4 , Agnieszka Mierczynska-Vasilev 4 , Krasimir Vasilev 4 , John D Hayball 1 2 5
  1. Sansom Institute, University of South Australia, Adelaide, SA, Australia
  2. Experimental Therapeutics Laboratory, Hanson Institute, Adelaide, SA, Australia
  3. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia
  4. Mawson Institute , University of South Australia, Adelaide, SA, Australia
  5. School of Medicine, University of Adelaide, Adelaide, SA, Australia

The use of biomaterial implants is an established part of medical practice, and has wide spread applications such as scaffolds for tissue repair, cardiac pacemakers, and glucose biosensors. However, the functionality of these biomaterials can be compromised by the development of a foreign body response (FBR); an acute sterile inflammatory reaction that may result in fibrotic encapsulation of the device. The aim of this study was explore two approaches in modulating the negative FBR outcomes.

The first approach was to determine the mechanisms that key innate immune cells play to initiate and drive the FBR. We first optimised the injection of PMMA beads (150 µm diameter) as an in vivo model of biomaterial implantation, negating the technical complications of surgical implants. Using this model, we found that AIM2 and NLRP3 inflammasomes played a role in the recruitment of macrophages and neutrophils, suggesting IL-1B is central to perpetuating the FBR. Furthermore, we observed that the beads had aggregated in vivo, allowing this ‘encapsulated’ biomaterial to undergo immunohistochemical analysis for proteins associated with the FBR including albumin, fibrinogen and collagen, as well as the presence of immune cells. We hope that further understanding these mechanisms will allow therapeutic interventions that target the respective pathways.

The second approach was to investigate the potential of modulating biomaterial surface characteristics prior to injection. The immobilisation of gold nanoparticles (up to 68 nm diameter) with different chemical coatings generated 16 individual surfaces. Comprehensive analysis of primary neutrophil and macrophage functionality was performed ex vivo, revealing that ‘rougher’ acidic surfaces were able to more dramatically reduce cytokine production. We are currently performing preliminary in vivo assessment of how acidic rough coatings affect biomaterial-induced inflammation. The outcomes of this project will allow rationally designed and manufactured biomedical implants with substrate surface characteristics that will enhance utility, function and clinical application.