# The role of CoCr nano metal degradation products (DPs) on alteration of DNA replication and repair mechanism in neural cell environment: Toxicology aspects

> **NIH NIH R03** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $79,950

## Abstract

Project Summary: The biological and environmental impacts of nanoparticles have been a great
health concern for decades. It is paramount for our well-being to evaluate the fundamental aspects of
the biological interactions of nanoparticles with cells and tissues. There is a gradual increase in the
number of reports on neurological clinical complications such as sensory disturbances (auditory
disturbances and visual loss), polyneuropathy and hypothyroidism, cardiomyopathy etc., associated
with degradation products (DPs) from Total Joint Replacements (TJRs). The recent reports on
polyneuropathy associated with CoCr nanoparticles highlight the importance of a mechanistic
evaluation of their interaction with neural cells, in the case of total hip replacement (THR). In fact, the
generated DPs from the implants are not just metal particles/debris alone, they may present as metal-
protein complexes, free metallic ions, inorganic metal salts/oxides and organic storage forms such as
hemosiderin. In addition, the bioactivity will vary significantly based on their physicochemical
characteristics. Unfortunately, these issues were not addressed in most of the previous investigations.
The primary reason for this knowledge gap is the limitations in simulating in vitro experimental set-up to
maintain the physiological environment.
The central hypothesis of this study is that the complex metal DPs may have significant role in inducing
neurodegeneration. The complex form of DPs generated from hip simulator will be the potent in vitro
model to study the implant mediated neurotoxicity and neurodegeneration in comparison to that of
processed DP as well as single type of metal ions. Hence, the proposed work has a high clinical
significance, as our primary goal is to determine the mechanisms by which physiologically relevant
CoCr wear nanoparticles cause neuronal dysfunction. With the support of strong preliminary data, the
hypothesis will be tested by pursuing two specific aims: Aim 1: To evaluate the physico-chemical
characteristics of DPs: We hypothesize that the DPs generated from the hip simulator will have
physico-chemical characteristics different from commercially available processed wear particles. This
aim will address the generation and characterization of physico-chemical characteristic of DPs from the
hip simulator to that of commercially available wear particles. Aim 2: To investigate neural cell toxicity
under acute and chronic exposure of DPs in a dynamic environment using Bioreactor on iPSC derived
neural cells: We hypothesize that CoCr DPs will cause genomic and mitochondrial DNA damage along
with oxidative stress, which further leads to neurodegeneration and may induce peripheral neuropathy.
The current aim will address the toxicity of DPs to iPSC derived neural cells, by maintaining the
dynamic in vivo joint condition. Two sub-aims are: 2a) Evaluation of neural cell response to CoCr
nanoparticles through toxicology tools 2b) Evaluation of molecular ...

## Key facts

- **NIH application ID:** 9928512
- **Project number:** 5R03NS111554-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Divya Rani Bijukumar
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,950
- **Award type:** 5
- **Project period:** 2019-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928512

## Citation

> US National Institutes of Health, RePORTER application 9928512, The role of CoCr nano metal degradation products (DPs) on alteration of DNA replication and repair mechanism in neural cell environment: Toxicology aspects (5R03NS111554-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928512. Licensed CC0.

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