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  • Glial scar mimicry on a digital microfluidics platform

    Glial scar mimicry on a digital microfluidics platform

Introduction | Spinal cord injury-on—a-chip

Spinal cord injury is an untreatable issue that affects millions of people every year all around the world. It results in partial or integral loss of mobility, confining a person suffering from it to live on a wheelchair or bedridden. On a molecular level, upon impact, the body reacts with the formation of a scar and a strong immune response that overtime becomes a chronic inflammation [1] However, the mechanisms of the injury remain poorly understood, hindering the disease’s progression prediction and, subsequently, the development of an effective treatment. The physical properties of the scar tissue are crucial for the molecular environment within the injury. We hypothesize that the density and tension of the scar fibers can be an inducing factor for the inflammatory response upon infiltrating cells.

Most spinal cord injury studies are conducted either with cell cultures on a plate, simple hydrogels that do not precisely replicate biological condition or in vivo studies that are extremely invasive for animals. We develop a microfluidic platform with scar tissue-mimicking hydrogel to study the mechanical cues for the inflammatory response of the organism.

Project | hydrogel synthesis and integration into a digital microfluidics platform

This project will be integrated in a bigger study targeting the replication of a spinal cord injury on-a-chip. We aim to replicate the physical characteristics of a glial scar and its influence on the inflammatory response of the organisms, namely macrophage polarization and support of chronic inflammation [2]. The first hydrogels will be produced with neutral synthetic scaffolds, replicating only the physical properties of the scar [3]. Subsequently, the hydrogel will be improved by incorporating more complex morphologies, regulating fiber orientation, heterogeneity of the tissue and capillary hydrogels, or, alternatively, a cell co-culturing within the hydrogel. You will be responsible for learning cell culture and microfabrication of fluidic chips, working towards bringing them together.

Figure 1. The cross section of the microfluidic platform where hydrogel patterns with different stiffness will be used to culture macrophages to determine the cell-material interactions.

 

Goal | milestones and achievements

The goals of this project are:

  1. To functionalize and characterize hydrogels with different density and tension, as well as structural heterogeneity, aiming to mimic a scar tissue.
  2. Study cell interaction with hydrogel in terms of cell viability and inflammatory biomarkers.

References

 

  1. Spinal cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses, Michael B. Orr, John C. Gensel, Neurotherapeutics, 2018
  2. Using extracellular matrix for regenerative medicine in the spinal cord, Fabio Zomer Volpato et al. Biomaterials, 2013
  3. Cell invasion in digital microfluidic microgel systems, Bingyu B. Li, et al, Science Advances, 2020