Synthesis and Degradation Behavior of Poly(Glycerol Sebacate)-Isophorone Diisocyanate Scaffolds Reinforced with Hydroxyapatite for Biomedical Applications

Poly(glycerol sebacate) (PGS) is a biodegradable elastomer with high potential for tissue engineering. However, its limited structural stability and degradation control restrict broader biomedical applications. This study presents an integrated fabrication strategy for highly porous PGS-IPDI scaffolds reinforced with two types of hydroxyapatite of distinct origin (HAP_B and HAP_ICMB). By combining low-temperature urethane crosslinking with thermally induced phase separation and salt leaching, we obtained scaffolds with interconnected micro–macroporous architectures and exceptionally high porosity (up to 98%). The comparative incorporation of phase-pure nanometric HAP_B and biphasic HAP_ICMB enabled the identification of composition-dependent differences in water uptake, structural stability, and mineralization tendencies. Furthermore, degradation behavior was systematically evaluated in four physiologically relevant media (PBS, SBF, artificial saliva, Ringer’s solution), revealing distinct degradation pathways associated with each environment. The results provide new insight into how hydroxyapatite type and incubation medium collectively govern the long-term performance of chemically crosslinked PGS-based scaffolds.