Distant tissue samples were collected (including brain, heart, kidney, liver, lung and spleen) to measure systemic levels of titanium. Gross macroscopic assessment at termination showed negligible changes in external as well as internal appearance of the injection site (Figure ). The small variation in gel mass (~0.2-0.3 g) between animals is likely due to variation introduced during injection and processing for histology (Figure ). Gel size remained largely constant over the duration of the experiment (Figure ). These results show that TiTannic gels are stable in vivo, which is in agreement with the in vitro disassembly studies (Figure and). TiTannic gels elicit a mild but persistent foreign body reaction. After excision, gels were processed for histology and stained with haematoxylin & eosin (H&E) to assess immune cell accumulation around the gel and Picrosirius red to visualize collagen deposition and the formation of a fibrotic capsule. The entire gel underneath the skin and embedded in subcutaneous tissue is shown in gave the foreign body capsule a homogenous appearance. Foreign body giant cells also started to appear at the border of the gel. From week 2 onwards, areas of increasing overlap between the gels and surrounding tissue were observed. This started as small pieces of gel within the surrounding infiltrate and developed towards cells which appear to have taken up pieces of gel (based on the change in color of their cytoplasm) (Figure ). A thin but homogenously organized fibrotic capsule was visible at later time points. As expected, most cells surrounding the gel stained positive for CD45, a pan-leukocyte marker (Figure ). The thicknesses of inflammatory infiltrate (Figure ) and fibrotic layer (Figure ) follow a similar curve with an early increase and a gradual decline over time. As expected, fibrosis develops with a brief delay as a result of immune cell infiltration. On the other hand, the thickness of the overlap layer between gel and cellular infiltrate increases over time (Figure ), as does the number of foreign body cells (Figure , Figure ).