Like bone mass, bone quality is specified in development, actively maintained post-natally, and disrupted by disease. The roles of osteoblasts, osteoclasts, and osteocytes in the regulation of bone mass are increasingly well defined. However, the cellular and molecular mechanisms by which bone quality is regulated remain unclear. Proteins that remodel bone extracellular matrix, such as the collagen-degrading matrix metalloproteinase (MMP)-13, are likely candidates that regulate bone quality. Using MMP-13 deficient mice, we examined the role of MMP-13 in the remodeling and maintenance of bone matrix and subsequent fracture resistance. Throughout the diaphysis of MMP-13-deficient tibiae, we observed elevated nonenzymatic crosslinking and concentric regions of hypermineralization, collagen disorganization, and canalicular malformation. These defects localize to the same mid-cortical bone regions where osteocyte lacunae and canaliculi exhibit MMP-13 and tartrate-resistant acid phosphatase (TRAP) expression, as well as the osteocyte marker Sclerostin. Despite otherwise normal measures of osteoclast and osteoblast function, dynamic histomorphometry revealed that remodeling of osteocyte lacunae is impaired in MMP-13−/− bone. Analysis of MMP-13−/− mice and their wild-type littermates in normal and lactating conditions showed that MMP-13 is not only required for lactation-induced osteocyte perilacunar remodeling, but also for the maintenance of bone quality. The loss of MMP-13, and the resulting defects in perilacunar remodeling and matrix organization, compromise MMP-13−/− bone fracture toughness and post-yield behavior. Taken together, these findings demonstrate that osteocyte perilacunar remodeling of mid-cortical bone matrix requires MMP-13 and is essential for the maintenance of bone quality.

Lead free ferroelectric ceramics of the KNN-LiTaO 3 -LiSbO 3 system were prepared using the (from ≈9500 to <6000). At temperatures below 300 •C however, the loss tangent in the doped samples (≈2.5 mol%) was much lower and steady when compared to the undoped one. The ferroelectric properties were slightly lowered with the addition of MnO2. The remnant polarisation (Pr) was lowered from ~18µC/cm2 to ~9µC/cm2, the coercive field (E c ) from ~ 8.5 kV/cm to ~ 6.2 kV/cm and the piezoelectric charge coefficient (d 33 ) decreased as well.

Calcium phosphate cements (CPCs) are injectable bone substitutes with a long clinical history because of their biocompatibility and osteoconductivity. Nevertheless, their cohesion upon injection into perfused bone defects as well as their long-term degradation behavior remain major clinical challenges. Therefore, the long-term degradation behavior of two types of α-tricalcium phosphate-based, apatite-forming CPCs was compared to a commercially available apatite-forming cement, that is HydroSet™ . Carboxyl methylcellulose (CMC) was used as cohesion promotor to improve handling properties of the two experimental cements, whereas poly (d, l-lactic-co-glycolic) acid (PLGA) microparticles were added to introduce macroporosity and stimulate CPC degradation. All three CPCs were injected into defects drilled into rabbit femoral condyles and explanted after 4, 12, or 26 weeks, after which the bone response was assessed both qualitatively and quantitatively. CPCs without PLGA microparticles degraded only at the periphery of the implants, while the residual CPC volume was close to 90%. On the contrary, bone ingrowth was observed not only at the periphery of the CPC, but also throughout the center of the implants after 26 weeks of implantation for the PLGA-containing CPCs with a residual CPC volume of approximately 55%. In conclusion, it was shown that CPC containing CMC and PLGA was able to induce partial degradation of apatite-forming CPCs and concomitant replacement by bone tissue.

Enhancing degradation of poorly degrading injectable calcium phosphate (CaP) cements (CPCs) can be achieved by adding poly(lactic-co-glycolic acid) (PLGA) microparticles, generating porosity after polymer degradation. CPC-PLGA has proven to be biodegradable, although its long-term biological performance is still unknown. Optimization of injectability could be achieved via addition of carboxymethyl cellulose (CMC). Here, we evaluated the long-term in vivo performance of CPC-PLGA with or without the lubricant CMC in comparison to the devitalized bovine bone mineral (DBBM) predicate device Bio-Oss. Rabbit femoral bone defects were injected with a CPC-formulation or filled with Bio-Oss granules. Samples were retrieved at 6 and 26 weeks. Material degradation for Bio-Oss was marginal, starting with 57% material remnants at implantation, 49% at 6 weeks, and 35% at 26 weeks, respectively. In contrast, CPC-PLGA and CPC-PLGA-CMC showed significant material degradation, starting with 100% material remnants at implantation, 56 and 78% at 6 weeks, and 8 and 21% at 26 weeks. Bone formation showed to be rapid for Bio-Oss, with 24% at 6 weeks, and a similar value (27%) at 26 weeks. Both CPC-PLGA and CPC-PLGA-CMC showed a continuous temporal increase in bone formation, with 13 and 6% at 6 weeks, and 44 and 32% at 26 weeks. This study showed that CPC-PLGA induces favorable bone responses with >90% degradation and >40% new bone formation after an implantation period of 26 weeks.

Lead-free piezoceramic potassium sodium niobate in its morphotropic composition was synthesized with abnormal grain growth. Ferroelectric domain patterns were imaged with piezoresponse force microscopy. Analysis of the domain structure at the morphotropic phase boundary revealed a coexistence of tetragonal and orthorhombic polarized domains in a single grain.