Injectable Ultrahigh Molecular Weight Fluorescent Copolymers for Bioimaging and Surgical Guidance

Abstract Injectable fluorescent polymers can enable real-time surgical guidance and bioimaging, but combining high transparency, low cellular uptake, clinically relevant viscosity, and hydrolytic stability remains challenging. Here, we report ultrahigh molecular weight (UHMW, >106 g mol−1) fluorescent copolymers synthesized by photoiniferter RAFT polymerization as injectable biomaterials for fluorescent ophthalmic viscosurgical devices (OVDs). Simulation results showed that fluorophore-rich segments collapse, promoting aggregation and self-quenching, and identified random monomer distribution with low fluorophore loading as key design criteria. Guided by these insights, N,N-dimethylacrylamide was copolymerized with fluorescein acrylate (0.1−1 mol %) to produce poly(DMA-co-FluA) with molecular weights up to 1.4 MDa and bright green fluorescence under blue illumination. Compared with (meth)acrylate analogues, the acrylamide backbone provided access to UHMW and optical clarity while offering greater intrinsic hydrolytic stability. The 1.4 MDa copolymer matched commercial Healon GV viscosity at ∼30 wt %, exhibited a pronounced frequency-dependent decrease in complex viscosity, reduced HEK293 cellular internalization, and enabled ex vivo porcine-eye OVD visualization and visual assessment of residual material.