The microstructure of polyphosphoesters controls polymer hydrolysis kinetics from minutes to years

The stability and degradation rates of polymers in aqueous media are critical factors for their biomedical ap-plications, as they must remain intact for a specific period of time before degrading or degrading on-demand to prevent potential accumulation and harmful effects. Polyphosphoesters (PPEs) are highly compatible with bio-logical systems, and the ester bonds in the backbone allow for hydrolytic degradation. In this study, we have demonstrated that the degradation rate of various PPEs can be precisely controlled by minor modifications to the side-chain and the binding pattern around the phosphorous center in the polymer backbone. We synthesized a systematic library of water-soluble PPEs using ring-opening polymerization, resulting in polyphosphates and in -chain or side-chain polyphosphonates. Specifically, we investigated the degradation rates of side-chain poly-phosphonates with different side-chain structures (methyl, ethyl, allyl, iso-or n-propyl) at pH = 8 and pH = 11. Our results indicate that the degradation mechanism is influenced by the type and size of the side-chain, as well as the pH. At pH = 11, hydrophilicity is a key factor, while at pH = 8, electron density on the phosphorus is crucial, leading to a random chain scission or a backbiting mechanism. We also observed that changing the binding pattern of the phosphorus or incorporating additional breaking points allowed us to tune the half-life times of the polymer from less than a day to several years. This study highlights the versatile stability of water-soluble PPEs, making them a promising option for various applications that require different hydrolysis rates, such as tissue regrowth.

Automated summary

In this study, the degradation rate of polyphosphoesters (PPEs) with different side-chain structures under different pH conditions was investigated. The degradation mechanism was found to be influenced by the type and size of the side-chain and pH. By modifying the structure of the polyphosphonates or introducing additional breaking points, the half-life of the polymer could be tuned. This study highlights the versatile stability and controllability of water-soluble PPEs, making them promising for various applications, such as tissue regrowth.