Adverse local tissue reactions (ALTRs) associated with metal particulate debris and/or ions released from modular junctions and other metal interfaces (e.g. prosthesis/bone) are the result of immune responses which have presented as granulomas, necrotic tissue, pseudotumors, etc. Although wear and corrosion (?tribocorrosion?) have long been recognized as the problems endangering the long term survival of orthopedic implants, much remains unknown about the interaction of host tissue with degradation products. We hypothesize that metal degradation products resulting from tribocorrosion are dynamically bioreactive (i.e. time-dependent), where implant debris is initially highly bioreactive and then decreases over time as it becomes more electrochemically stable. Once validated in this study, our development of a ?Tribocorrosion Bioreactor? will allow direct mechanistic investigations between degradation products and cells, and will enable preclinical testing of meta-stable tribocorrosion products that are generated in situ. Here, we will evaluate if real time metal tribocorrosion products are excessively reactive aseptic stimuli eliciting both innate (macrophage) and adaptive (lymphocyte) immuno-reactivity and, thus, differ from more time-stabilized complexes formed from the same debris. Demonstrating the phenomenon of time-dependent implant debris reactivity is critical to understanding the clinical impact of freshly produced metal implant debris from both wear and corrosion. It will provide a significant leap forward into the next generation of in vitro testing of orthopedic materials.

Public Health Relevance

A tribocorrosion bioreactor that will result in meta-stable wear debris that closely reflects true in vivo generated degradation products, unlike current manufactured and/or isolated particles, will improve the predictive value of preclinical in vitro testing. It will further advance our mechanistic understanding of the reactivity of implant debris in general and help to avoid metal interfaces which generate harmful debris, as may occur in improperly designed modular junctions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB024039-01A1
Application #
9455400
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Rampulla, David
Project Start
2017-09-30
Project End
2019-07-31
Budget Start
2017-09-30
Budget End
2018-07-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Orthopedics
Type
Schools of Medicine
DUNS #
068610245
City
Chicago
State
IL
Country
United States
Zip Code
60612