Perspectives on the Inflammatory, Healing, and Foreign Body Responses to Biomaterials and Medical Devices

James Anderson1 and Stephanie Cramer2,    1Department of Pathology and Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA,    2Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

An overview presents early host responses to biomaterials immediately following implantation. Inflammation, wound healing, and foreign body reaction (FBR) constitute a tissue-response continuum occurring over the first days and weeks following implantation. The extent of tissue injury caused by implantation varies with implantation procedures and the host response can be time-dependent, organ-dependent, and species-dependent. Early resolution of acute and chronic inflammatory reactions lead to transient granulation tissue and wound healing, while a FBR at tissue/material interface is initiated by monocyte/macrophage adhesion with fusion of macrophages forming foreign body giant cells. Inflammation generally resolves in the first weeks following implantation leading to fibrous capsule development and fibrous encapsulation of the implant. The early host responses following implantation provide the basis for determining host–device biocompatibility and ultimately lead to success or failure of a biomaterial or medical device.

Keywords

Inflammation; biomaterials; foreign body giant cell; macrophage; wound healing

Contents

Introduction

The host response to biomaterials, medical devices, and prostheses ultimately determines the success or failure and the downstream efficacy of the respective implant in the clinical setting. Table 2.1 provides a global perspective of in vivo complications of medical devices and provides both material-dependent and biologically dependent (i.e., host response-dependent) modes and mechanisms of failure, many of which are interactive and synergistic. Inflammation, healing, and foreign body reactions (FBRs) are the earliest host responses following implantation and provide the basis for determining host–device compatibility.

The most commonly used term to describe an appropriate host response to biomaterials in the form of a medical device is biocompatibility. A simplistic definition of biocompatibility is those materials which do not induce an adverse tissue reaction. A more helpful definition of biocompatibility is the ability of a material to perform with an appropriate host response in a specific application (Williams, 1987, 2008). This definition is helpful in that it links material properties or characteristics with performance (i.e., biological requirements, specific applications, specific medical device, or biomaterial used as a medical device). The “appropriate host response” implies identification and characterization of tissue reactions and responses that could prove harmful to the host and/or lead to ultimate failure of the biomaterial, medical device, or prosthesis through biological mechanisms. Viewed from the opposite perspective, the “appropriate host response” implies identification and characterization of the tissue reactions and responses critical for the successful use of the biomaterial or medical device. Biocompatibility assessment is considered to be a measure of the magnitude and duration of the adverse alterations in homeostatic mechanisms that determine the host response (Anderson, 2001). Safety assessment or biocompatibility assessment of a biomaterial or medical device is generally considered to be synonymous.

Inflammation, wound healing, and the FBR are generally considered part of the tissue or cellular host response to injury (Kumar et al., 2005). Table 2.2 lists the sequence/continuum of these events following injury. Overlap and simultaneous occurrence of these events should be considered (e.g., the FBR at the implant interface may be initiated with the onset of acute and chronic inflammation). From a biomaterials perspective, placing a biomaterial in an in vivo environment requires injection, insertion, or surgical implantation, all of which injure the tissue or organ involved.

The placement procedure initiates a response to injury by the tissue, organ, or body, and mechanisms are activated to maintain homeostasis. Obviously, the extent of injury varies with the implantation procedure. A more detailed description of the innate immune-response contribution to these initial events is provided in Chapters 6 and 7. The degrees to which the homeostatic mechanisms are perturbed, and the extent to which pathophysiologic conditions are created and undergo resolution, are a measure of the host response to the biomaterial and may ultimately determine its biocompatibility. Although it is conceptually convenient to separate homeostatic mechanisms into blood–material or tissue–material interactions, it must be remembered that the various components or mechanisms involved in homeostasis are present in both blood and tissue, are inextricably linked, and are a part of the physiologic continuum. Furthermore, it must be noted that the host response is tissue-dependent, organ-dependent, and species-dependent.

Blood–Material Interactions/Provisional Matrix Formation

Immediately following injury, changes in vascular flow, caliber, and permeability occur. Fluid, proteins, and blood cells escape from the vascular system into the injured tissue in a process called exudation. The changes in the vascular system, which also include the hematologic alterations associated with acute inflammation, are followed by cellular events that characterize the inflammatory response. The chemical factors that mediate many of the vascular and cellular responses of inflammation and the initial host response are described in detail in numerous reviews and in Chapter 5.

Blood–material interactions and the inflammatory response are intimately linked; in fact, early responses to injury involve mainly blood and vasculature. Regardless of the implantation site, the initial inflammatory response is activated by injury to vascularized connective tissue (Table 2.3). Inflammation serves to contain, neutralize, dilute, or wall-off the injurious agent or process (Inflammation: Basic Principles and Clinical Correlates, 1999) In addition, the inflammatory response initiates a series of events that may heal and reconstitute the implant site through replacement of the injured tissue with native parenchymal cells, fibroblastic scar tissue, or a...