The function and efficacy of implanted devices and biomaterials, such as cardiovascular devices, biosensors, and tissue engineering material, can be compromised by host responses to foreign material. These immune responses include inflammation, chronic activation of the immune system, and formation of fibrous capsules around the biomaterial or implant. Current approaches to diminish these responses have been only partially successful, and there is a need to explore alternative strategies. In this study, we will investigate the use of LAIR-1 binding sites in collagen to modulate inflammation and foreign body response. Collagen, the most abundant protein in natural extracellular matrices (ECM), can modulate the function of cells through its native interaction sites. One such interaction involves the leukocyte-associated Ig-like receptor (LAIR-1), a transmembrane glycoprotein that has been shown to inhibit the activation of many types of immune cells. We hypothesize that local immune responses to implanted surfaces, such as inflammation, fibrosis, and wound-healing, can be modulated by attaching LAIR-1 binding ligands to these surfaces. To test our hypothesis, we propose the following aims: (1) fabricate surfaces conjugated with LAIR-1 sites, (2) evaluate the ability of LAIR-1 binding sites to inhibit macrophage activation in vitro, and (3) evaluate the in vivo immunological response to implanted material containing LAIR-1 binding sites. We will utilize our collagen synthesis technology that uniquely enables us to fabricate full-length collagen variants with precisely-defined sequences and locations of cell interaction sites. In vitro investigations will evaluate the effects of LAIR-collagen interactions on macrophages by quantifying activation markers. Material implantation studies will examine the effects of LAIR-collagen interactions on macrophages, neutrophils, other immune cells, and the foreign body response using histology, in vivo bioluminescent imaging, and immunofluorescence. This work will develop and evaluate a new class of biomimetic materials that are tailored to specifically interact with and inhibit the activity of immune cells. This strategy is designed to mitigate chronic inflammation of implantable materials. Such materials could increase the longevity and function of implantable devices in the body and could be used as immunomodulatory substrates for tissue engineering.
This work will develop and evaluate a new class of materials that is tailored to specifically interact with and inhibit the activity of immune cells. This strategy is designed to mitigate chronic inflammation of implantable materials. Such materials could increase the longevity and function of implantable devices in the body and could be used as immunomodulatory components for regenerating tissue.
|Kim, Yoon Kyung; Chu, Shu-Hui; Hsieh, Jessica Y et al. (2017) Incorporation of a Ligand Peptide for Immune Inhibitory Receptor LAIR-1 on Biomaterial Surfaces Inhibits Macrophage Inflammatory Responses. Adv Healthc Mater 6:|