Foreign Body Reaction to Subcutaneous Implants.

Subcutaneously implanted materials trigger the host's innate immune system, resulting in the foreign body reaction. This reaction consists of protein adsorption on the implant surface, inflammatory cell infiltration, macrophage fusion into foreign body giant cells, fibroblast activation and ultimately fibrous encapsulation. This series of events may affect the function of subcutaneous implants, such as inhibition of drug diffusion from long-acting drug delivery depots and medical device failure. The foreign body reaction is a complex phenomenon and is not yet fully understood; ongoing research studies aim to elucidate the cellular and molecular dynamics involved. Recent studies have revealed information about the specific role of macrophages and their differential activation towards pro- and anti-inflammatory states, as well as species differences in the timing of collagen deposition and fibrosis. Understanding of the diverse processes involved in the foreign body reaction has led to multiple approaches towards its negation. Delivery of tissue response modifiers, such as corticosteroids, NSAIDs, antifibrotic agents, and siRNAs, has been used to prevent or minimize fibrosis. Of these, delivery of dexamethasone throughout the implantation period is the most common method to prevent inflammation and fibrosis. More recent approaches employ surface modifications to minimize protein adsorption to 'ultra-low' levels and reduce fibrosis. However, the diverse nature of the processes involved in the foreign body reaction favor the use of corticosteroids due to their wide spectrum action compared to other approaches. To date, combination approaches, such as hydrophilic coatings that reduce protein adsorption combined with delivery of dexamethasone are the most effective.