A three-dimensional in vitro model to quantify inflammatory response to biomaterials

Area of Science:

• Biomaterials Science
• Immunology
• Tissue Engineering

Background:

• In vivo models are standard for biomaterial-host response, but in vitro models offer better control and cost-effectiveness for quantifying cellular and molecular contributions.
• Existing in vitro models often lack the complexity to fully recapitulate physiological healing environments.

Purpose of the Study:

• To develop and validate a 3-D in vitro co-culture model using human fibroblasts and monocytes.
• To investigate the foreign body response to biomaterials by monitoring cellular morphology and inflammatory cytokine production.
• To establish a versatile platform for studying material-host interactions and predicting patient-specific biocompatibility.

Main Methods:

• Co-culturing human fibroblasts and monocytes in a 3-D tissue model.
• Observing morphological changes in cells.
• Quantifying inflammatory cytokine production using multiplex quantitative protein analysis.
• Challenging the co-culture model with poly(lactic-co-glycolic acid) (PLGA).

Main Results:

• Monocultures of fibroblasts or monocytes produced minimal cytokine release.
• Co-culturing fibroblasts and monocytes led to significant morphological changes and increased inflammatory cytokine release.
• In the presence of poly(lactic-co-glycolic acid), co-cultured cells secreted elevated levels of IL-1β, IL-6, GM-CSF, and TNF-α.

Conclusions:

• The 3-D in vitro co-culture model effectively mimics cellular interactions and inflammatory responses relevant to biomaterial implantation.
• This model serves as a foundation for a flexible platform to study material-host interactions with engineered cells or reporter systems.
• The model shows potential for predicting patient-specific biocompatibility by utilizing individual patient cells.