Sections were stained with haematoxylin and eosin (H&E) and Picrosirius Red/Fast Green. All reagents were purchased from Sigma-Aldrich. Sections were also stained for the pan-leukocyte marker CD45 using anti-mouse CD45 antibody clone: 30-F11 (BioLegend, UK) and detection using HRPlabelled goat anti-rat IgG (Vector Laboratories, USA). The DAB substrate kit (Vector Laboratories, UK) was used according to manufacturer's instructions. After final dehydration, slides were mounted with DPX mountant (Sigma-Aldrich) and analyzed using a Nikon Eclipse TE2000 inverted microscope or a LMD7000 microscope (Leica microsystems, UK). Measurements were obtained using Fiji and included the total area of the gel, the thickness of the layer of infiltrate and fibrosis surrounding the gel, and the thickness of the material/cell overlap layer. The number of foreign body giant cells were counted manually as shown in Figure . Titanium measurements and biodistribution. Titanium was measured in blood, urine and tissue samples with a Thermo Element 2 magnetic sector field HR-ICP-MS (Thermo Fisher Scientific, Germany). Calibration standards were prepared by dilution from a custom stock solution (QMX Laboratories Limited, UK) with a titanium concentration traceable to NIST SRM 3162a Lot 130925.