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 Fe₃O₄. However, the effects of Fe₃O₄ loading on degradation and biosafety remain unclear, which limits the in vivo translation of PGD/Fe₃O₄ composites. This study aimed to clarify the relationship between Fe₃O₄ content, degradation behavior, and gastrointestinal biosafety, thereby informing the design of PGD/Fe₃O₄ devices. Five formulations containing 0, 5, 10, 20, or 40 wt% Fe₃O₄ 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 Fe₃O₄ incorporation without altering the principal polyester backbone. Under both degradation conditions, the degradation percentage and medium acidification decreased with increasing Fe₃O₄ 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 Fe₃O₄ loading improved structural persistence during degradation but narrowed the biosafety window. Within the present formulation set, composites containing up to 20 wt% Fe₃O₄ provided the most favorable balance between degradation behavior and intestinal biosafety, supporting their further development for biomedical devices.