? The implantation of biomaterials into soft tissues leads to the development of the foreign body response (FBR) that can interfere with the function of the implant and eventually lead to implant failure. In general, due to the FBR a largely avascular and dense collagenous capsule forms around biomaterials and scaffolds. A hallmark of the FBR is the formation and persistence of foreign body giant cells (FBGC) on the surface of the implant, a process that is indicative of a chronic inflammatory response. In addition, FBGC have been shown to cause extensive surface damage to a variety of biomaterials and cause the release of microparticles that can have toxic effects. Furthermore, a role for FBGC in promoting biomaterial encapsulation has been proposed. Thus, unlike a wound healing response that is self-limiting, the FBR can last for the duration of the implantation period. Despite the prominence of FBGC at implantation sites, little is known about their formation in vivo. We have found that MCP-1-null mice display compromised FBGC formation that is associated with reduced biomaterial damage.
In Specific Aim 1 of this proposal we aim to fully characterize the FBR in the MCP-1-null mice.
In Specific Aim 2 we will focus on monocyte recruitment and FBGC formation and, by selective temporal inhibition of MCP-1, we will dissect its contribution to these processes.
In Specific Aim 3 we will utilize an in vitro assay to investigate the molecular and biochemical cues that are influenced by the lack of MPC-1. Finally, in Specific Aim 4 a gene delivery approach will be employed to limit FBGC formation, increase foreign body capsule neovascularization and shift the FBR towards a wound healing phenotype. It is expected that a shift towards a wound healing-like response should enhance biocompatibility by preventing damage and extending the lifespan of implants. Overall, this application proposes a novel approach to target the FBR, primarily by the selective targeting of host-derived molecular processes. ? ?
| Loye, Ayomiposi M; Kinser, Emily R; Bensouda, Sabrine et al. (2018) Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass. Sci Rep 8:8758 |
| MacLauchlan, Susan C; Calabro, Nicole E; Huang, Yan et al. (2018) HIF-1? represses the expression of the angiogenesis inhibitor thrombospondin-2. Matrix Biol 65:45-58 |
| Morris, Aaron H; Stamer, Danielle K; Kunkemoeller, Britta et al. (2018) Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds. Biomaterials 169:61-71 |
| Shayan, Mahdis; Padmanabhan, Jagannath; Morris, Aaron H et al. (2018) Nanopatterned bulk metallic glass-based biomaterials modulate macrophage polarization. Acta Biomater 75:427-438 |
| Kunkemoeller, Britta; Kyriakides, Themis R (2017) Redox Signaling in Diabetic Wound Healing Regulates Extracellular Matrix Deposition. Antioxid Redox Signal 27:823-838 |
| Padmanabhan, Jagannath; Augelli, Michael J; Cheung, Bettina et al. (2016) Regulation of cell-cell fusion by nanotopography. Sci Rep 6:33277 |
| Sawyer, Andrew J; Kyriakides, Themis R (2016) Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization. Adv Drug Deliv Rev 97:56-68 |
| Morris, Aaron H; Chang, Julie; Kyriakides, Themis R (2016) Inadequate Processing of Decellularized Dermal Matrix Reduces Cell Viability In Vitro and Increases Apoptosis and Acute Inflammation In Vivo. Biores Open Access 5:177-87 |
| Moore, Laura Beth; Sawyer, Andrew J; Saucier-Sawyer, Jennifer et al. (2016) Nanoparticle delivery of miR-223 to attenuate macrophage fusion. Biomaterials 89:127-35 |
| Padmanabhan, Jagannath; Kyriakides, Themis R (2015) Nanomaterials, inflammation, and tissue engineering. Wiley Interdiscip Rev Nanomed Nanobiotechnol 7:355-70 |
Showing the most recent 10 out of 42 publications
