Hydrogen bonds govern hydrolytic degradation and bulk properties of electrospun poly(ester-arylate) scaffolds

Understanding biomaterial degradation at the molecular level is crucial for designing scaffolds for regenerative medicine. This study elucidates the influence of hydrogen bonding on the in vitro degradation of electrospun poly(ester-arylate). Degradation exhibits an initial rapid phase (67% loss in number-average molecular weight ( M n ) by day 50), followed by a slow phase (an additional 11% M n loss by day 200). Despite progressive chain scission, the glass transition temperature ( T g ) increases from 30 to 56 °C, accompanied by broad endothermic transitions. Spectroscopic analyses reveal the formation of hydrogen bonding by degradation products containing alcoholic and carboxylic end groups. Molecular dynamics (MD) simulations provide quantitative validation of both intra- and intermolecular hydrogen bonding. These interactions form transient hydrogen-bonding networks that restrict the mobility of degraded polymer segments and thereby explain the erosion mechanism and thermal signatures. By establishing a mechanistic link between a molecular-level structural feature (hydrogen bonding) with macroscopic degradation behavior (chain scission, network formation, and change in mobility), this work provides design principles for developing next-generation biodegradable scaffolds in drug delivery and regenerative medicine.