Abstract
A wide range of implanted biomaterials, tissue engineered scaffolds, and devices interact with the immune system via complex and not well-understood mechanisms. This is due, in part, to the diversity of tissue- and cell-specific elicited responses that are broadly characterized as the foreign body response (FBR). In general, FBR leads to encapsulation by a collagenous and largely avascular capsule that limits functions and lifespan of implants. This outcome is especially at odds with tissue engineering and regenerative medicine strategies that intend to integrate with or recruit cells from the native tissue environment to build or restore functional tissue. The FBR and other unwanted inflammatory processes may also add further damage to the already injured or diseased environment.
It is appreciated that biomaterial sources such as native or synthetic, and properties including porosity, topography, stiffness, charge, and wettability can impact the FBR. 1 Interactions between implant surfaces and other components and proteins and cells in tissues involve the innate immune system with macrophages playing a central role in mediating FBR outcomes. Polarization of macrophages and acquisition of activation states unique to the FBR have attracted extensive interest and numerous studies have shed light on this process. 2 Moreover, many investigators have developed strategies to modulate macrophage polarization toward attenuation of the FBR in the context of tissue engineered constructs. 3 In some cases, balanced macrophage activity between prohealing and proinflammatory phenotypes is essential to tissue repair.4–6 Collectively, findings from these studies highlight the importance of this cell type and innate immunity in general. Importantly, it is recognized that the successful employment of tissue-engineered constructs relies on enhancement of tissue remodeling and overall growth without excessive fibrosis or other unwanted reactions.
Engagement of components of adaptive immunity in the FBR, including T and B cells, has also been demonstrated, 7 specifically, the participation of these cell types in pro- or anti-fibrotic responses toward natural or synthetic biomaterials. Therefore, it is important to consider communication between the innate and adaptive arms of immunity and their cross-talk with cells of mesenchymal origin responsible for extracellular matrix deposition and remodeling. These processes can be altered in many pathological conditions such as diabetes or autoimmune diseases, suggesting that FBR outcomes can be influenced by the overall status of the immune system. For example, implant studies in diabetic animals showed an exacerbated FBR.
Interestingly, distinct approaches targeting either components of the immune system or employing biomaterial modifications have resulted in almost complete amelioration of the FBR in experimental systems. For example, biomechanical stimulation, inhibition of inflammatory signals, and controlling scaffold porosity, or surface chemistry have been shown to limit encapsulation and, in some cases, improve implant/cell functions.8–11 Collectively, these studies highlight the importance of both immunity and biomaterial properties in driving the FBR or beneficial healing and should inform the development of strategies with clinical potential.
The focus of this special issue is centered on the above themes and aims to contribute to our understanding of the immune response in the context of the FBR and how it might hinder or enhance tissue-engineering goals. It contains descriptions of approaches involving modulations and modifications of immune reactions and biomaterial properties, respectively. These include immunomodulatory strategies and exploration of biomechanical and other inputs in cell- and tissue-specific approaches.