RT Journal Article
SR Electronic
T1 Zwitterionic hydrogels modulate the foreign body response in a modulus-dependent manner
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 195719
DO 10.1101/195719
A1 LE Jansen
A1 LD Amer
A1 E Y-T Chen
A1 TV Nguyen
A1 LS Saleh
A1 TS Emrick
A1 WF Liu
A1 SJ Bryant
A1 SR Peyton
YR 2017
UL http://biorxiv.org/content/early/2017/09/28/195719.abstract
AB Reducing the foreign body response (FBR) to implanted biomaterials will enhance their in vivo performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost and ease of use. PEG hydrogels can elicit chronic inflammation upon implantation, but recent evidence has suggested that extremely hydrophilic, zwitterionic hydrogels can reduce the FBR to particles and gels. To expand on this approach, we synthesized hydrogels of co-monomers PEG and the zwitterion phosphorylcholine (PC) to quantify the combinatorial effects of modulus and hydrophilicity on the FBR. Surprisingly, hydrogels with the highest amount of zwitterionic co-monomer elicited the highest FBR we observed. Lowering the hydrogel modulus (165 kPa to 3 kPa), or PC content (20 wt% to 0 wt%), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment to these hydrogels. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design.HighlightsModulus and zwitterion content independently modulate the foreign body response to soft hydrogelsSoft PEG hydrogels synthesized with the zwitterionic PC co-monomer are pro-inflammatory as modulus is increasedThe chemical and physical properties of hydrogels influence the foreign body response via macrophage recruitment and protein adsorption