Current bone graft substitutes are either inert or need supplementation with stem cells or growth factors that are expensive and difficult to administer in an individualized manner. Our new graft substitute induces the expression of growth factors and promotes the bone regeneration itself without any supplementation of cells and growth factors. This graft substitute is based on two amorphous microparticles: (i) BONE FORMATION ENERGY AND SUBSTRATE SUPPLIER: morphogenetically active calcium polyphosphate (Ca-polyP) and (ii) BIOSEEDS FOR BONE MINERALIZATION: calcium carbonate (ACC). Both microparticles have been entrapped into poly lactic-co-glycolic acid (PLGA) microspheres for implant fabrication. These microspheres are linked together to form bioscaffolds/implants by an outer glue-like matrix (“sealant”), composed of above mentioned Ca-polyP microparticles that hardens by contact with body fluid and becomes immediately bioactive.
Experimental results show that Ca-polyP, a naturally occurring polymer, and ACC are biocompatible and bioresorbable which act anabolically on bone forming in vitro. To demonstrate the morphogenetic activity of polyP in vivo, animal studies (rat calvarial defect model) have been performed. Implants/discs (8-mm diameter) were prepared from the microspheres and inserted into 10-mm diameter defects and the kinetics of bone regeneration was evaluated. Immunohistochemistry analysis revealed that fibril formation is markedly enhanced with polyP implants compared to β-TCP control. Both the formation of COL-I and the expression of ALP are upregulated, as well as the extent of mineralization around/within the polyP implants. Nanoindentation experiments showed that after 56 d the hardness/stiffness (reduced Young’s modulus) of the tissue around/within the polyP implants reached values of ~2 MPa which are close to the value of original calvarial bone, whereas the hardness around/within the control β-TCP implants was much lower (<1 MPa).
Our data demonstrate that amorphous and resorbable inorganic polyP is morphogenetically active in vitro and in vivo and is a promising dental and orthopedic bone regeneration implant biomaterial.
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