Biodegradable, Biocompatible, and Crosslinkable Polymers Enable Biosafe and Sustainable Soft Gels and Nanogels for Biomedical Applications.

To date, more biodegradable polymers have been developed due to the growing recognition of the advantages of biodegradable and biocompatible polymers for biomedical applications. In this study, we introduce the synthesis and characterization of innovative polymers that incorporate biodegradable backbones composed of trimethylolpropane and adipic acid moieties and biocleavable side chains containing pyridyl disulfide groups. Notably, their synthesis is straightforward and catalyst-free under ambient conditions, minimizing potential toxicity and immune responses caused by catalyst residues in polymer materials. The new polymers have desired molecular weight (Mn: 18.8 kDa) with a narrow dispersion (PDI: 1.32) and offer complete biodegradability, biocompatibility, crosslinking capabilities, and opportunities for covalent chemical modifications. These features make them particularly suitable for use in biomedical materials and devices. Additionally, due to their unique properties, these polymers have been successfully formulated into polymeric gels and nanogels, which are biodegradable as well. Using a near-infrared fluorescent probe as a model cargo, we demonstrated the creation of a biosafe and sustainable nanogel system for agent delivery, with an average size of approximately 70 nm. In these nanogels, agent molecules are covalently attached to the scaffold, thereby avoiding uncontrolled premature release and burst release in the bloodstream and mitigating associated systemic toxicity and side effects. The nanogels can also be easily functionalized with targeting ligands for disease-specific delivery. These polymers induced minimal toxicity toward human cells and displayed excellent in vivo biocompatibility, highlighting the significant potential of their polymeric gels and nanogels for a broad spectrum of biomedical applications.