In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (¹H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1β, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.

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.