Associate Professor University of California, Irvine, United States
Introduction Although bone morphogenetic protein type 2 (BMP2) is extremely effective at inducing bone formation, where and how much bone forms is under poor control. Aragonite is the lustrous polymorph of calcium carbonate found within inner side of seashells. Aragonite-nucleating proteins exert great control over the size and location of the minerals formed. Biomineralization researchers have identified several aragonite-nucleating nacre matrix proteins with osteogenic properties. When we bound these proteins to biomaterials, they exerted high spatial control over mineralization by mammalian cells.
Materials and Methods We covalently bound nacre-derived and bone-derived proteins to a variety of biomaterials. Specifically, we used water soluble matrix extracted from nacre, a synthesized nacre peptide (n16N), bone sialoprotein (BSP), BMP2, and dentin matrix protein 1 (DMP1). These were bound directly or via a PEG-acrylate linker to glass slides in patterns or randomly. These were also bound to hydrogel surfaces in patterns or randomly and within bulk hydrogels randomly to evaluate the potential for spatial control using the bound proteins. We evaluated the materials’ ability to induce mineralization from solution and their ability to induce osteoprogenitors (MSCs and preosteoblasts) to form mineralization within patterns.
Results, Conclusions, and Discussions When acellular mineralization was evaluated, all materials induced mineralization from solution with the exception of PEG-DMP1. However, when cellular mineralization was evaluated, all materials induced osteoprogenitors to form mineralization, including PEG-DMP1. Only BMP2 and nacre proteins could induce MSC osteodifferentiation within patterns. Moreover, only nacre proteins could induce osteoblasts to mineralize within patterns. This ability of nacre’s to control mineralization may lead to orthopedic biomaterials capable of spatially controlling bone formation and eliminating ectopic bone growth.