The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

Abstract

The foreign body response describes the non-specific immune response to implanted foreign materials (Coleman et al., 1974; Anderson, 2001; Luttikhuizen et al., 2006). It is characterised by the infiltration of inflammatory cells to the area to destroy or remove this material, followed by the repair or regeneration of the injured tissue. However, if the foreign material cannot be phagocytosed and removed, the inflammatory response persists until the material becomes encapsulated in a dense layer of fibrotic connective tissue (Anderson, 2001) which shields it from the immune system and isolates it from the surrounding tissues. The foreign body response has developed as a protective mechanism to limit exposure to toxic or allergenic materials, but also presents a problem for modern medicine. Biomedical devices now serve in a vast number of medical applications, including orthopedic, dental and breast implants, pacemakers, sutures, vascular grafts, heart valves, intraocular and contact lenses, controlled drug delivery devices and biosensors. This response is common to all medical devices or prostheses implanted into living tissue, and ultimately results in fibrosis or fibrous encapsulation which compromises the efficiency of the device and frequently leads to device failure (reviewed in Anderson et al., 2008). For example, the contraction of the myofibroblast-rich capsules around breast implants leads to ‘implant shrinkage’ (Abbondanzo et al., 1999) while encapsulating tissue prevents the diffusion of molecules to biosensors or from implanted drug delivery pumps (Anderson et al., 2008). The response to implanted materials varies depending on their physicochemical properties (eg shape, size, surface chemistry, morphology and porosity; see Morais et al (2010) for review). Jones et al (2007; 2008) have shown that macrophage adhesion and fusion is higher on hydrophobic surfaces than hydrophilic/neutral surfaces while McBane and co-workers (McBane et al., 2011) found that compared with 2-dimensional films, 3-dimensional porous polyurethane scaffolds induced a low inflammatory, wound healing phenotype and may * Jane Mooney, Bing Zhang, Sani Jahnke, Sarah-Jane Le, Yu-Qian Chau, Qiping Huang, Hao Wang, Gordon Campbell and Julie Campbell Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia  552 Regenerative Medicine and Tissue Engineering - Cells and Biomaterials reduce the negative effects of the foreign body reaction. However despite attempts to identify non-immunogenic implant materials, or to mask surface properties of the implant material with biocompatible coatings (Quinn et al., 1995; Shive & Anderson, 1997; Draye et al., 1998; Paradossi et al., 2003), the inflammatory response cannot be completely avoided (Cao et al., 2008). This is thought to be due to the adsorption of proteins such as fibrinogen, complement and antibodies to the material immediately after implantation (Kao et al., 1999; Hu et al., 2001; Gretzer et al., 2006). Thus as outlined by Wisniewski et al (2001), the key to long-term functionality of implanted devices such as glucose sensors is modulation of the tissue response. In order to do this, it is important to first understand the mechanisms underlying the foreign body response to implanted biomaterials, the cells involved and their molecular mediators.