Nowadays, no barrier membrane serves all purposes of bone augmentation. This study aimed to fabricate a semi-rigid shell barrier system composed of a semi-rigid shell and a covering membrane or a semi-resorbable barrier membrane, based on polycaprolactone (PCL) and biphasic calcium phosphate (BCP) for guided bone regeneration (GBR). A shell and a covering membrane were fabricated by a solvent casting technique based on PCL (70) and BCP (30). The experimental groups were a semi-rigid shell, an airdried membrane, a buffered membrane, and a commercial d-PTFE as a control. Physico-chemical, mechanical properties, and in vitro biocompatibility with osteoblasts and fibroblasts cells were evaluated in all groups. The fabricated materials had rough surfaces with a homogeneous distribution of BCP particles on one side and a smooth surface on the opposite side. The airdried membrane presented a rougher surface on both top and bottom sides (Sq=605.45nm, 556.82nm) than the semi-rigid shell (310.74nm, 424.56nm) and the buffered membrane (277.9nm, 306.98nm), respectively. The pore sizes of the airdried membrane (25-40μm) were larger than the semi-rigid shell (5-40μm) and the buffered membrane (5-25μm). The porosities of the airdried and buffered membranes (∼40%) were higher than the semi-rigid shell (∼20%) significantly (p<0.05). All fabricated materials were hydrophilic, with the lowest water contact angle in the semi-rigid shell (54.7°±3.06°), then the airdried (61.15°±4.76°), and the buffered (75.74°±2.8°) respectively. The semi-rigid shell resisted a higher load on compressive force (18.82±2.72N) than the d-PTFE membrane (4.23±0.5N). The tensile stress of the buffered membrane (2.544±0.19MPa) was not different from the d-PTFE (2.908±0.12MPa) but was higher than the airdried membrane (1.302±0.13MPa) significantly (P<0.05). The airdried membrane had reached 100% swelling ability within 1h, which was significantly faster than the buffered membrane (12h) and the semi-rigid shell (7 days), and they were slowly degraded by lysozyme at 6 months (airdried: 24.88%±0.96%, buffered: 13.67%±0.55%, and semi-rigid: 8.62%±0.88%). All fabricated membranes showed no toxicity to osteoblast and fibroblast cells. The semi-rigid shell and the covering membranes demonstrated suitable physical and mechanical properties, and biocompatibility, and can be assembled as the novel semi-rigid shell barrier system for bone regeneration.