Degradation behavior and biosafety of PGD/Fe3O4 shape-memory composites: An in vitro and in vivo study

Poly(glycerol dodecanoate) (PGD) is a biodegradable shape-memory elastomer that can be rendered magnetically responsive by incorporating Fe 3 O 4 . However, the effects of Fe 3 O 4 loading on degradation and biosafety remain unclear, which limits the in vivo translation of PGD/Fe 3 O 4 composites. This study aimed to clarify the relationship between Fe 3 O 4 content, degradation behavior, and gastrointestinal biosafety, thereby informing the design of PGD/Fe 3 O 4 devices. Five formulations containing 0, 5, 10, 20, or 40 wt% Fe 3 O 4 were prepared and designated as ION-0, ION-5, ION-10, ION-20, and ION-40. The composites were evaluated by FTIR, SEM/EDS, lipase-mediated degradation under dynamic and static conditions, Caco-2 assays, and 70-day oral exposure in mice. FTIR confirmed Fe 3 O 4 incorporation without altering the principal polyester backbone. Under both degradation conditions, the degradation percentage and medium acidification decreased with increasing Fe 3 O 4 content. Conditioned degradation media from ION-0, ION-5, ION-10, and ION-20 preserved Caco-2 viability and proliferation and maintained ZO-1 and Occludin expression, whereas ION-40 reduced junctional marker expression despite limited overt cytotoxicity. After daily gavage for 70 days, no obvious pathological lesions were observed in the heart, liver, spleen, lung, or kidney in any group, except for the intestine, where evident ileal injury and decreased ileal ZO-1 and Occludin expression were observed in the ION-40 group, whereas the other groups remained well tolerated. Overall, increasing Fe 3 O 4 loading improved structural persistence during degradation but narrowed the biosafety window. Within the present formulation set, composites containing up to 20 wt% Fe 3 O 4 provided the most favorable balance between degradation behavior and intestinal biosafety, supporting their further development for biomedical devices. • Fe 3 O 4 slowed PGD enzymatic degradation in a loading-dependent manner • PGD through 20 wt% Fe 3 O 4 preserved intestinal barrier tolerance • 40 wt% Fe 3 O 4 impaired Caco-2 junctions and induced ileal injury • A practical Fe 3 O 4 loading window was defined for GI-facing PGD devices