Dealing with the Foreign-Body Response to Implanted Biomaterials: Strategies and Applications of New Materials

Macrophage phenotypes in tissue repair and the foreign body response: Implications for biomaterial-based regenerative medicine strategies.

The immune microenvironment in cartilage injury and repair

All implanted biomaterials are targets of the host's immune system. While the host inflammatory response was once considered a detrimental force to be blunted or avoided, in recent years, it has become a powerful force to be leveraged to augment biomaterial-tissue integration and tissue repair. In this review, we will discuss the major immune cells that mediate the inflammatory response to biomaterials, with a focus on how biomaterials can be designed to modulate immune cell behavior to promote biomaterial-tissue integration. In particular, the intentional activation of monocytes and macrophages with controlled timing, and modulation of their interactions with other cell types involved in wound healing, have emerged as key strategies to improve biomaterial efficacy. To this end, careful design of biomaterial structure and controlled release of immunomodulators can be employed to manipulate macrophage phenotype for the maximization of the wound healing response with enhanced tissue integration and repair, as opposed to a typical foreign body response characterized by fibrous encapsulation and implant isolation. We discuss current challenges in the clinical translation of immunomodulatory biomaterials, such as limitations in the use of in vitro studies and animal models to model the human immune response. Finally, we describe future directions and opportunities for understanding and controlling the biomaterial-immune system interface, including the application of new imaging tools, new animal models, the discovery of new cellular targets, and novel techniques for in situ immune cell reprogramming.

Immunomodulatory Biomaterials for Tissue Repair.

© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Macrophages play a central role in orchestrating immune responses to foreign materials, which are often responsible for the failure of implanted medical devices. Material topography is known to influence macrophage attachment and phenotype, providing opportunities for the rational design of “immune-instructive” topographies to modulate macrophage function and thus foreign body responses to biomaterials. However, no generalizable understanding of the inter-relationship between topography and cell response exists. A high throughput screening approach is therefore utilized to investigate the relationship between topography and human monocyte–derived macrophage attachment and phenotype, using a diverse library of 2176 micropatterns generated by an algorithm. This reveals that micropillars 5–10 µm in diameter play a dominant role in driving macrophage attachment compared to the many other topographies screened, an observation that aligns with studies of the interaction of macrophages with particles. Combining the pillar size with the micropillar density is found to be key in modulation of cell phenotype from pro to anti-inflammatory states. Machine learning is used to successfully build a model that correlates cell attachment and phenotype with a selection of descriptors, illustrating that materials can potentially be designed to modulate inflammatory responses for future applications in the fight against foreign body rejection of medical devices.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.201903392

Immune Modulation by Design: Using Topography to Control Human Monocyte Attachment and Macrophage Differentiation

Summary Implanted medical devices often elicit adverse foreign body responses whereby macrophages play a central role. Here, we identify simple polymers that instruct different immunological responses by modulating macrophage attachment and polarization to pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotypes. These immune-instructive polymers were discovered using in vitro high-throughput polymer microarray screening of diverse (meth)acrylate and (meth)acrylamide libraries. The bioinstructive polymer function is validated in vivo within a murine foreign body model. Differential tissue response from polymers coated on silicone tubing is consistent with in vitro macrophage pro- and anti-inflammatory responses. Polymer structure-cell response relationships are modeled using machine learning to reveal molecular descriptors useful for describing immune-instructive polymers. Analysis of the protein layer adsorbed to polymers from media suggests that thicker layers may relate to M1-like phenotype whereas the reverse relates to M2-like response. Such simple polymers are readily translatable into immune-instructive biomaterials for application in the medical device and regenerative medicine fields.

Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo

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Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo