Research

Our Approach

Musculoskeletal infection (MSKI) — including implant-associated infection, such as periprosthetic joint infection and fracture-related infection — remains one of the most challenging complications in orthopedic surgery. Treatment failure is driven by bacterial persistence across protected niches: biofilm, immune-shielded abscess communities, and bacteria residing within bone and host cells. These compartments evade conventional antibiotics and are the central barrier to effective treatment. The MSKI Laboratory integrates molecular biology, immunology, preclinical models, and advanced imaging to define mechanisms of persistence and develop targeted therapeutics.

In vivo bioluminescence imaging of Staphylococcus aureus infection in a mouse model of periprosthetic joint infection
In vivo bioluminescence: tracking bacterial infection at the knee joint implant site in a mouse model of periprosthetic joint infection.
Confocal microscopy of intracellular MRSA-GFP (green) within host cells; nuclei stained with DAPI (cyan) and actin (red)
Confocal microscopy: intracellular MRSA-GFP (green) within host cells (DAPI, cyan; actin, red).
Scanning electron microscopy of Staphylococcus aureus biofilm architecture on a titanium implant surface
Scanning electron microscopy: S. aureus biofilm architecture on a titanium implant surface.
Three-dimensional micro-CT reconstruction of infected mouse bone showing osteolysis and periprosthetic bone remodeling around an intramedullary titanium implant
3D micro-CT reconstruction: osteolysis and reactive bone remodeling surrounding an infected intramedullary femoral implant.

An Example of Our Therapeutic Focus

Anti-DNABII Monoclonal Antibody Therapy for Periprosthetic Joint Infection

Mechanism of anti-DNABII monoclonal antibody therapy: DNABII protein sequestration destabilizes the biofilm extracellular matrix, collapsing the scaffold and exposing bacteria to antibiotics and host immune clearance
Anti-DNABII antibody mechanism: sequestration of DNABII linchpin proteins collapses the biofilm scaffold, releasing bacteria for clearance.

Collapsing the Biofilm to Overcome Resistance

Biofilms render bacteria up to 8,000-fold more tolerant to antibiotics and are the central driver of treatment failure in implant-associated infection. DNABII proteins crosslink extracellular DNA (eDNA) at critical junctions, serving as the structural linchpin of the biofilm matrix. Anti-DNABII monoclonal antibodies sequester these proteins, causing rapid collapse of the biofilm scaffold and liberating bacteria from the biofilm that are sensitized to conventional antibiotics and exposed to host immune clearance.

Research Platforms

Agar zone-of-inhibition assay: a gentamicin-loaded titanium nanotube wire (left) creates a clearance zone in a Staphylococcus aureus lawn, while an unloaded wire (right) does not; a gentamicin paper disc serves as the positive control

Preclinical Models & Antimicrobial Assays

Clinically relevant mouse models of implant-associated infection, paired with in vitro biofilm systems and zone-of-inhibition assays, quantify antimicrobial efficacy from the bench to preclinical testing.

Fluorescence confocal microscopy of immune cells

Host–Pathogen Biology

Cell and molecular biology platforms dissect intracellular bacterial persistence, immune evasion mechanisms, and tissue-resident host defense.

Scanning electron micrograph of a coated and infected orthopedic implant surface harvested from a mouse model of periprosthetic joint infection

Implant Surface Characterization

High-resolution scanning electron microscopy characterizes implant surface topography, coating performance, biofilm, and bacterial adhesion at the material interface.

X-ray of mouse skeleton with an intramedullary femoral implant

Longitudinal Radiographic Imaging

Micro-CT and plain X-ray imaging enable serial assessment of peri-implant bone remodeling, osteolysis, and infection-associated pathology over the disease course.

In vivo bioluminescence imaging of Staphylococcus aureus infection at a knee joint orthopedic implant site

Longitudinal Bioluminescence Imaging

In vivo bioluminescence imaging of engineered luminescent bacterial strains permits real-time, non-invasive tracking of bacterial burden at the implant site, quantifying infection dynamics and therapeutic response within the same animal over time.

H&E histology of bone and periprosthetic tissue of distal femur harvested from a mouse model of periprosthetic joint infection

Histology & Immunohistochemistry

Histologic & immunohistochemical analyses characterize infection-associated tissue pathology, inflammatory cell infiltration, and bacteria and biofilm presence.

Sofija and Jorge O. Galante Orthopedic Building at Rush University Medical Center in Chicago

Clinical Studies

Biomarker discovery, diagnostics, and therapeutic evaluation.