A series of novel injectable and photo-crosslinkable poly(propylene fumarate) (PPF)-co-polyhedral oligomeric silsesquioxane (POSS) copolymers are synthesized via two-step polycondensation to improve both stiffness and toughness and to promote biological performance of bone tissue engineering scaffolds. The viscoelastic behavior of uncrosslinked PPF-co-POSS and the thermal, mechanical, and surface characteristics of photo-crosslinked PPF-co-POSS are investigated as well as the degradation behavior and microscopic POSS domain structures at various weight compositions of POSS (ϕPOSS). Tensile and compressive moduli and facture toughness are enhanced for crosslinked PPF-co-POSS when POSS nanocages are well distributed and their crystallinity is completely confined in the networks. Decreases in these mechanical properties are observed at higher ϕPOSS because of decreased crosslinking density and larger POSS aggregates. The mechanical properties are correlated with in vitro mouse pre-osteoblastic MC3T3-E1 cell functions including cell attachment, spreading, proliferation, differentiation, and gene expression, which all maximize at ϕPOSS of 10%.