Understanding the host response to cell-laden poly(ethylene glycol)-based hydrogels

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Immunology

Background:

• Poly(ethylene glycol) (PEG)-based hydrogels are utilized as in situ cell carriers for tissue engineering applications.
• The foreign body reaction (FBR) is a critical host response that can influence the success of implanted biomaterials.

Purpose of the Study:

• To investigate the hypothesis that the FBR affects encapsulated cells within PEG hydrogels and subsequently influences the FBR's severity.
• To elucidate the interaction between encapsulated fibroblasts, macrophages, and PEG hydrogels in the context of the FBR.

Main Methods:

• Fibroblasts were encapsulated in RGD-modified PEG hydrogels, and macrophages were cultured on top to simulate in vivo interactions.
• Macrophage inflammatory phenotype was induced using lipopolysaccharide.
• Cell-laden and acellular PEG hydrogels were implanted subcutaneously in mice for 2, 7, and 28 days.

Main Results:

• Activated macrophages altered fibroblast gene expression, reducing extracellular matrix production while increasing VEGF and IL-1β.
• Fibroblasts modulated macrophage phenotype, upregulating iNOS, IL-1β, and TNF-α.
• Encapsulated fibroblasts initially secreted collagen but showed decreased tissue deposition and cellularity over time; encapsulated fibroblasts increased acute inflammation but not fibrosis.

Conclusions:

• The host response, particularly the FBR, significantly impacts encapsulated cells within PEG hydrogels.
• There is a complex interplay between encapsulated cells and the host immune system that can affect tissue engineering outcomes.
• The findings highlight the critical need to consider the host response when designing synthetic scaffolds for tissue regeneration.