Search

Demineralized bone matrix (DBM), has been used as a bone-graft material because of its osteoconductivity and osteoinductivity. However, the previous research report that supports the single use of DBM is limited by its rapid resorption caused by the lack of calcium and phosphate. β-Tricalcium phosphate (TCP) is an enriched calcium phosphate material suitable for bone healing with osteoconductive properties. In this study, we have developed injectable bone graft by the loading two kinds of TCP in DBM particles and thermo-sensitive DBM-derived hydrogel (hDBM). TCP powder (pTCP) and TCP granules (gTCP) were loaded into hDBM and DBM, respectively. The bone formation effect was investigated according to the morphological features of TCP. Residual growth factor concentrations were investigated; microstructure and morphology were characterized by SEM. In-vitro studies showed that hDBM/DBM/pTCP and hDBM/DBM/gTCP bone grafts were biocompatible and could promote osteogenesis by up-regulating the expression of Runx2 and OPN, bone-related genes. In-vivo studies using the rabbit-femur defect model revealed that the implanted hDBM/DBM/pTCP bone graft showed similar histology to that of fibrous dysplasia with the expression of CD68, whereas hDBM/DBM/gTCP showed good bone formation. Loading of gTCP in place of pTCP was noticed as an effective way to improve bone regeneration in an injectable hDBM/DBM hydrogel-based bone graft.

Teeth extraction is inevitable in the case of progressive or alveolar bone destructing chronic periodontitis. Unfortunately, the resulting bone defects may lead to many side effects. Here, we developed a novel dental-bone substitute to preserve the extraction socket for hemostasis and bone regeneration. Hyaluronic acid-gelatin hydrogel (HG) polymers, β-tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP) ceramics were fabricated using freeze-drying methods. The HG/TCP/BCP plug was prepared to be easily applied by pouring the mixture of HG and TCP into the shell-shaped mold, followed by placing the sponge type of BCP in the core portion of the mold compared to HG/TCP and collagen plugs. In vitro studies showed that HG/TCP and HG/TCP/BCP plugs were cytocompatible and could promote osteogenesis by upregulating the expressions of bone-related genes COL1, RUNX2, ALP, and OPN. The rabbit-femur defect model revealed that the implanted HG/TCP/BCP plug, which showed excellent hemostatic property, promote bone regeneration with a high rate of collagen distribution along with ALP and OPN expressions more than could the HG/TCP plug at 3 months after implantation, whereas the collagen plugs just filled with chondrocytes for cartilages formation. The HG/TCP/BCP plug should be considered for potential dental applications for one-step socket preservation.

The present work addresses the performance of polycaprolactone (PCL) coating on fluoride treated (MgF2) biodegradable ZK60 magnesium alloy (Mg) for biomedical application. MgF2 conversion layer was first produced by immersing Mg alloy substrate in hydrofluoric acid solution. The outer PCL coating was then prepared using dip coating technique. Morphology, elements profile, phase structure, roughness, mechanical properties, invitro corrosion, and biocompatibility of duplex MgF2/PCL coating were then characterized and compared to those of fluoride coated and uncoated Mg samples. The invivo degradation behavior and biocompatibility of duplex MgF2/PCL coating with respect to ZK60 Mg alloy were also studied using rabbit model for 2 weeks. SEM and TEM analysis showed that the duplex coating was uniform and comprised of porous PCL film (~3.3 μm) as upper layer with compact MgF2 (~2.2 μm) as inner layer. No significant change in microhardness was found on duplex coating compared with uncoated ZK60 Mg alloy. The duplex coating showed improved invitro corrosion resistance than single layered MgF2 or uncoated alloy samples. The duplex coating also resulted in better cell viability, cell adhesion, and cell proliferation compared to fluoride coated or uncoated alloy. Preliminary invivo studies indicated that duplex MgF2/PCL coating reduced the degradation rate of ZK60 Mg alloy and exhibited good biocompatibility. These results suggested that duplex MgF2/PCL coating on magnesium alloy might have great potential for orthopedic applications.

Background: Amyloid precursor protein (APP) is cleaved by β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) to produce β-amyloid (Aβ), a critical pathogenic peptide in Alzheimer's disease (AD). Aβ generation can be affected by the intracellular trafficking of APP or its related secretases, which is thus important to understanding its pathological alterations. Although sorting nexin (SNX) family proteins regulate this trafficking, the relevance and role of sorting nexin-4 (SNX4) regarding AD has not been studied yet. Methods: In this study, human brain tissue and APP/PS1 mouse brain tissue were used to check the disease relevance of SNX4. To investigate the role of SNX4 in AD pathogenesis, several experiments were done, such as coimmunoprecipitation, Western blotting, immunohistochemistry, and gradient fractionation. Results: We found that SNX4 protein levels changed in the brains of patients with AD and of AD model mice. Overexpression of SNX4 significantly increased the levels of BACE1 and Aβ. Downregulation of SNX4 had the opposite effect. SNX4 interacts with BACE1 and prevents BACE1 trafficking to the lysosomal degradation system, resulting in an increased half-life of BACE1 and increased production of Aβ. Conclusions: We show that SNX4 regulates BACE1 trafficking. Our findings suggest novel therapeutic implications of modulating SNX4 to regulate BACE1-mediated β-processing of APP and subsequent Aβ generation. [ABSTRACT FROM AUTHOR]