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 Infection developing after fracture fixation is one of the persisting and debilitating complications of orthopedic trauma surgery, and its importance grows with the rise of antibiotic-resistant bacterial strains. I dedicated my PhD to finding and testing endogenous non-antibiotic compounds called metabolites, based on emerging evidence that they uphold and tune immune cell function – making metabolites exciting new ingredients in biomaterials engineering to modulate the biology of bone healing and infection. 

The complexity of bone infections and metabolism is daunting, but it’s exactly what drives me to design meaningful in vitro studies.

Infection is one of the persistent complications of orthopedic trauma surgery – developing in more than ¼ of open fractures.

Fracture related infection (FRI) is a bacterial infection of bone and surrounding tissue developing after fracture and reconstruction surgery. It causes non-union and implant failure, and greatly increases morbidity in patients. Managing FRI is complicated by the diffusion-limiting physiology of bone, the ability of bacteria to form biofilms on dead bone and implant surfaces, and surging microbial antibiotic resistance - all limiting the effect of systemic antibiotic treatment. Current treatment therefore relies on two-step revision surgery: removing the implant, debriding infected tissue, and inserting antibiotic loaded spacers; followed by a second surgery, after the infection is resolved, to remove the spacer and re-implant fixation hardware. Current research focuses on developing antimicrobial materials for permanent implantation, preventing infection or enabling one-step revision surgery.

My work as a PhD student is dedicated to finding and testing non-antibiotic compounds on their ability to prevent and combat FRI, and to incorporate them into calcium phosphates for bone regeneration. Specifically, I focus on endogenous small molecules called metabolites (e.g. cysteine) to avoid the challenges of antibiotic resistance. As a relatively new research area, metabolites have been recognized to play a pivotal role in immune cell regulation – for example they drive macrophage polarization to either pro- or anti-inflammatory phenotypes. My goal is to find metabolite changes characteristic of FRI and test if substitution of depleted metabolites restores macrophage function. I started this journey at the Baltic Biomaterial Center of Excellence (BBCE), using our metabolomics facility to screen for depleted metabolites in FRI samples from our collaborators at the AO Research Institute. Together, we established in vitro experiments to study bacteria-macrophage crosstalk and assess how selected metabolites influence this crosstalk. This more complex setup brings our experiments closer to patient-like conditions, and is aimed at finding metabolites that ultimately improve the function of immune cells challenged with bacteria.

Using metabolites as active ingredients in biomaterials engineering is an exciting new approach to modulate the biology of bone healing and infection. We are currently analyzing in parallel how exactly our favorite metabolites influence macrophage biology, and developing amorphous calcium phosphate-metabolite composites to test the resulting materials.

Theresa Schiemer

Affiliation:
Riga Technical University, Baltic Biomaterial Center of Excellence

Country:
Latvia

E-mail:
Theresa.schiemer@rtu.lv

LinkedIn Profile:
linkedin.com/in/theresa-schiemer-b06102243