Molecular Weight-dependent Diffusion, Biodistribution, and Clearance Behavior of Tetra-armed Poly(ethylene glycol) Subcutaneously Injected into the Back of Mice

Four-armed poly(ethylene glycol) (PEG)s are essential hydrophilic polymers extensively utilized to prepare PEG hydrogels, which are valuable tissue scaffolds. When hydrogels are used in vivo , they eventually dissociate due to the cleavage of the backbone structure. When the cleavage occurs at the cross-linking point, the hydrogel elutes as an original polymer unit, i.e., four-armed PEG. Although four-armed PEGs have been utilized as subcutaneously implanted biomaterials, the diffusion, biodistribution, and clearance behavior of four-armed PEG from the skin are essential. This paper investigates time-wise diffusion from the skin, biodistribution to distant organs, and clearance of fluorescence-labeled four-armed PEGs with molecular weight ( Mw ) ranging from 5–40 kg/mol subcutaneously injected into the back of mice. Changes over time indicated that the fate of subcutaneously injected PEGs is M w-dependent. Four-armed PEGs with M w ≤ 10 kg/mol gradually diffused to deep adipose tissue beneath the injection site and distributed dominantly to distant organs, such as the kidney. PEGs with M w ≥ 20 kg/mol stagnated in the skin and deep adipose tissue, and were mainly delivered to the heart, lung, and liver. The fundamental understanding of the M w-dependent behavior of four-armed PEGs is beneficial for preparing biomaterials using PEGs, providing a reference in the field of tissue engineering. ### Competing Interest Statement The authors have declared no competing interest.