Understanding and Controlling the Immune Response to Implantable Biomaterials

When non-biological (e.g., synthetic) materials are implanted into higher organisms, they elicit a foreign body response (FBR) that begins with non-specific protein adsorption, followed by inflammation, and eventual resolution with the formation of an avascular fibrous capsule that walls off the implant from the surrounding tissue. Despite extensive studies describing the FBR, the molecular and cellular mechanisms that lead to the FBR are not well understood. Our group utilizes transgenic mouse models to study pathways and innate immune cells to identify those that are responsible for the FBR. In the context of tissue engineering when cells are present within a scaffold, the severity of the FBR can negatively impact cells and their ability to produce new tissue. Our group is working to identify pathways that lead to the FBR and to use this knowledge to develop new materials that attenuate the FBR. More recently, we have extended our studies to microparticles as a potential delivery vehicle to target immune cells. Our overarching goal is to develop biomaterials, which when placed in vivo, attenuates inflammation, facilitates host tissue remodeling at the material-tissue interface, and promotes functional integration of the device and tissue engineering scaffold.

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E. Grey, J. McClendon, J. Suresh, S. Alper, W.J. Janssen, S.J. Bryant. Thiol-Ene Microparticles: Their Synthesis, Characterization, and Uptake by Macrophages. ACS Biomaterials Science & Engineering. 9(7): 4223-4240 (2023).

L.S. Saleh, L.D. Amer, B.J. Thompson, T. Danhorn, J.R. Knapp, S.L. Gibbings, S. Thomas, L. Barthel, B.P. O’Connor, W. Janssen, S. Alper, S.J. Bryant. Mapping macrophage polarization and origin during the progression of the foreign body response to a poly(ethylene glycol) hydrogel implant. Advanced Healthcare Materials. 11(9): e2102209 (2022). DOI: 10.1002/adhm.202102209.

L.S. Saleh, C. Vanderheyden, A. Frederickson, and S.J. Bryant. Prostaglandin E2 and its receptor EP2 modulate macrophage activation and fusion in vitro. ACS Biomaterial Science and Engineering. 6(5): 2668-2681 (2020).

L.D. Amer, L.S. Saleh, C. Walker, S. Thomas, W.J. Janssen, S. Alper, S.J. Bryant. Inflammation via myeloid differentiation primary response gene 88 signaling mediates the fibrotic response to implantable synthetic poly (ethylene glycol) hydrogels. Acta biomaterialia. (2019).

D. Faulón Marruecos, L.S. Saleh, H.H. Kim, S.J. Bryant, D.K. Schwartz, J.L. Kaar. Stabilization of fibronectin by random copolymer brushes inhibits macrophage activation. ACS Applied Bio Materials (2019).

Swartzlander MD, Blakney AK, Amer LD, Hankenson KD, Kyriakides TR, Bryant SJ. Immunomodulation by mesenchymal stem cells combats the foreign body response to cell-laden synthetic hydrogels. Biomaterials. 41:79-88 (2015).