Synthetic Bone Substitutes Differently Influence Human and Porcine Adipose-derived MSCs

Swine are a proper animal model in bone tissue engineering for their similarities with humans in terms of bone healing, anatomy, and composition. Since cell-scaffold constructs are fundamental for bone regeneration, we studied the effects of two bone substitutes, RO-1 and RO-2, on human (h) and porcine (p) adipose-derived mesenchymal stem/stromal cells (ASCs), in vitro. At first, we show that both cell types display stable proliferation rates, high clonogenicity, and an increase in ALP activity, collagen release, ECM calcification and osteopontin expression, when osteo-induced for 2 weeks. The scaffolds are biocompatible, and both ASCs nicely adhere to them; however, while hASCs normally proliferate in the presence of biomaterials, a slight reduction in growth rate is observed for pASCs. Besides, ASC osteodifferentiation is influenced by biomaterials: RO-1 increased ALP activity and collagen release on human ASCs compared to cells in monolayer and seeded on RO-2, independently of the presence of osteogenic stimuli. Differently, pASCs cultured on scaffolds show 10 folds decrease of ALP activity compared to cells cultured in monolayer. In addition, RO-2 stimulates just ALP activity, while the presence of RO-1 induces mainly collagen production. In conclusion, both biomaterials are biocompatible, however human and porcine ASCs interact differently with them suggesting the requirement of cell-specific in vitro tests before moving to in vivo model.