Foreign Body Response

What is the foreign body response?

immune meditated response to an implant material resulting in dense fibrosis scaring

When is the foreign body good?

Fighting infection, protecting the material, shrapnel/debris

Steps of the foreign body response

• Adsorption of autologous(from own body) proteins(seconds)

• Recruitment of macrophages (minutes)

• Formation of early granuloma(small, typically noncancerous area of inflammation) (hours)

• Establishment of foreign body granuloma (days)

• Vascularization of foreign body granuloma (weeks)

Why is thick granuloma potentially harmful?

1. Bad for implants with bio-functional surfaces (limits transport)

2. Bad for tissue homeostasis

How to assess the FBR?

1. in vitro - add protein soup, study adsorption investigate surface properties

2. Ex vivo - take tissue from an organism and study interactions

3. In vivo - implant, sacrifice, histology

How to dampen FBR

1. Surface engineering

2. Elute immunohematology drugs

How can we dampen the FBR? Surface engineering

a) Engineer surface charge (modify WEDL) to modulate which proteins are adsorbed

b) Create rough surfaces to suppress macrophage attachment

c) Orthogonally append hydrophilic polymers to suppress fouling

d) Make surface hydrophobic (in some cases)

e) Append extracellular matrix proteins to mimic native tissues

Encapsulate immunomodulatory drugs

a) Suppress macrophage activation (and inflammation)

b) Reduce recruitment of new macrophages, decreasing granuloma size

c) Increase production of vascular endothelial growth factor (VEGF)

• VEGF promotes angiogenesis, or blood vessel formation

• Blood vessels help remove toxins and increase blood flow to

granuloma, further reducing inflammation

Encapsulate immunomodulatory drugs Limitations

Anti-inflammatory drugs downregulate endogenous

VEGF, which can inhibit angiogenesis long-term

biofilms

Forms on medical devices, implants, and surgical tools. Very difficult to kill once formed and can lead to chronic inflammation and infection.

What factors affect biofilm formation?

• Surface free energy (wettability)

• Would it be hydrophobic or hydrophilic?

• Hydrophilic would promote, hydrophobic would prevent

• But both super hydrophobic and –philic surfaces have been shown to prevent biofilm formation

• Surface charge (WEDL)

• Surface roughness / topography