Investigating Immunomodulatory Biomaterials for Preventing the Foreign Body Response

Abstract

Implantable biomaterials represent the forefront of regenerative medicine, providing platforms and vessels for delivering a creative range of therapeutic benefits in diverse disease contexts. However, the chronic damage resulting from implant rejection tends to outweigh the intended healing benefits, presenting a considerable challenge when implementing treatment-based biomaterials. In response to implant rejection, proinflammatory macrophages and activated fibroblasts contribute to a synergistically destructive process of uncontrolled inflammation and excessive fibrosis. Understanding the complex biomaterial-host cell interactions that occur within the tissue microenvironment is crucial for the development of therapeutic biomaterials that promote tissue integration and minimize the foreign body response. Recent modifications of specific material properties enhance the immunomodulatory capabilities of the biomaterial and actively aid in taming the immune response by tuning interactions with the surrounding microenvironment either directly or indirectly. By incorporating modifications that amplify anti-inflammatory and pro-regenerative mechanisms, biomaterials can be optimized to maximize their healing benefits in harmony with the host immune system.

Keywords: biomaterials; foreign body response; immunomodulation; macrophages.

Figure 1

Immune-focused foreign body reaction. This figure illustrates the different steps of the foreign body response due to biomaterial implantation. Plasma proteins within the body interact with the biomaterial triggering the initiation of immune cell recruitment, including lymphocytes, neutrophils, monocytes and eventually macrophages. Macrophages in turn release a variety of cytokines such as NF-κB, TNF-α, TGF-β, IL-1β, IL-6, and IL-8, which further enhance the recruitment of macrophages, promote phagocytosis, and contribute FBGC. The presence of FBGC leads to the secretion of proteases, acid hydrolases, ROS, fibroblasts, and generation of ECM, ultimately resulting in the development of a fibrotic capsule surrounding biomaterial.

Figure 2

Tunable properties of biomaterials. This figure depicts different tunable properties of biomaterials that promote tissue integration. Modifications are made to the composition of biomaterials through various approaches. These include altering (A) chemistry composition and flexibility, (B) implementing surface modifications, (C) adjusting the biodegradability properties and (D) modifying the delivery methods of the biomaterial. These are some strategies that aim to optimize the biomaterial characteristics and interactions with the host tissue. Reproduced with permission of reference [27].

Figure 3

Immune system inducing tissue regeneration. This figure depicts the immunomodulatory properties of biomaterials to mitigate the foreign body response. The immune system releases proinflammatory cytokines and anti-inflammatory cytokines to increase tissue regeneration to increase wound healing [70].