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Biomimetic Dicalcium Phosphate Cements for Improved Bone Regeneration

出版	McGill University Libraries, 2019
URL	http://books.google.com.hk/books?id=oas0ygEACAAJ&hl=&source=gbs_api

註釋"Decellularized bone matrices (e.g. bone allografts) are excellent materials for bone regeneration; however, the reasons for their unique regenerative properties are still not well understood. Besides growth factors such as bone morphogenic proteins (BMPs), it seems that other bone extracellular matrix (ECM) components including trace metals and proteins have a role in stimulating bone regeneration. On the other hand, it remains unclear how these bone-derived materials promote regeneration without inducing unfavorable host immune reactions (i.e. foreign body response). Unveiling the mechanisms underlying these actions could help improve the regenerative performance of synthetic bone replacement materials. Synthetic calcium phosphate (CaP) bioceramics, especially dicalcium phosphates, are very useful for bone regeneration; however, their regenerative performance requires substantial improvement. It seems that mimicking the composition of bone ECM could be a promising strategy to achieve this target. We hypothesized that modifying the composition of synthetic CaP bioceramics with trace metals or proteins of bone ECM would improve their in vivo integration and regenerative performance. To test our hypothesis, we conducted two separate studies to assess the effect of incorporating these constituents on the bone regenerative functionality of CaP bioceramics. In the first study, we introduced, for the first time, a simple approach to fabricate CaP bioceramic cements containing a biomimetic elemental composition using a bovine bone-derived apatite material. We demonstrated the superior in vivo regenerative performance of these cements compared to control cements made from synthetic CaP reagents. This finding helps explain the reason behind the excellent regenerative properties of natural bone grafts in general, and inorganic bone xenografts (e.g. Bio-Oss) in particular. It also opens the door towards the possibility to fabricate customized 3D-printed xenografts for a wide range of bone regeneration applications. The second study presented a novel method to improve biomaterial/host integration and modulate the immune responses in a way that favors bone healing. We discovered that coating CaP bioceramics with bone ECM protein extracts, especially those rich in calcium binding proteins, modulated their interaction with plasma proteins in vitro by reducing the surface proteomic signature of the innate immune response proteins. In addition, this coating attenuated the inflammatory response upon in vivo implantation, which created an environment that favors osteoblastogenesis and inhibits osteoclastogenesis, thus, resulting in increased new bone formation around the bioceramics. We also showed that those bone ECM proteins could be 3D-printed into customized hydrogel scaffolds with improved bone regeneration capabilities. According to our results, it can be concluded that bone ECM trace elements and specific proteins play an important role in presenting the excellent bone regeneration outcomes obtained with natural bone grafts. We believe that these findings pave the way to a new generation of synthetic biomaterials that would eventually be able to replicate bone-derived graft materials and offer potential clinical benefits for patients suffering from bone loss problems."--