Mg bone implant: Features, developments and perspectives

The treatment of end-stage liver disease and acute liver failure remains a clinically relevant issue. Although orthotopic liver transplantation is a well-established procedure, whole-organ transplantation is invasive and increasingly limited by the unavailability of suitable donor organs. Artificial and bioartificial liver support systems have been developed to provide an alternative to whole organ transplantation, but despite three decades of scientific efforts, the results are still not convincing with respect to clinical outcome. In this Review, conceptual limitations of clinically available liver support therapy systems are discussed. Furthermore, alternative concepts, such as hepatocyte transplantation, and cutting-edge developments in the field of liver support strategies, including the repopulation of decellularized organs and the biofabrication of entirely new organs by printing techniques or induced organogenesis are analysed with respect to clinical relevance. Whereas hepatocyte transplantation shows promising clinical results, at least for the temporary treatment of inborn metabolic diseases, so far data regarding implantation of engineered hepatic tissue have only emerged from preclinical experiments. However, the evolving techniques presented here raise hope for bioengineered liver support therapies in the future.

Liver support strategies: cutting-edge technologies.

Magnesium (Mg) and its alloys are potential metals for biodegradable implants because of several benefits, including a reduction of stress shielding effect in the implant for orthopedic application and the elimination of the step of a second surgery to remove the implant. On the other hand, unexpected degradation can cause the Mg to collapse, and the implant fails; thus, many studies have been done to control the rate of degradation of Mg alloys. Heterogeneous corrosion of these implants leads to rapid mechanical properties loss, limiting the clinical applications. Adding ceramic reinforcements to the Mg matrix as so-called Mg nanocomposites is one method to enhance the ductility and also mechanical properties of the Mg alloys without a noticeable weight cost. Good corrosion resistance and noticeable mechanical properties of the Mg-based nanocomposites have developed their applications. However, it is difficult to uniformly disperse the ceramic-based nanoparticles as reinforcements in the Mg matrix and attain desired characteristics. As a result, selecting Mg-ceramic composite production methods and reinforcing types to overcome Mg restriction and increase the favorable material features based on their applications is critical. As a result, this review study focus on the different fabrication techniques and reinforcement material types and their influence on Mg-ceramic composites’ mechanical characteristics, in vitro corrosion performance and biocompatibility. The potential applications, and future research ideas of Mg matrix nanocomposite are investigated. The existing successes in this field are discussed, and future investigation areas are identified in order to boost the usage of degradable Mg-based composites.

Overview of magnesium-ceramic composites: mechanical, corrosion and biological properties

Hydroxyapatite [Ca10(PO4)6(OH)2; HAp] is the mineral component of vertebrate hard tissues and an important raw material for biomaterials. The HAp crystal belongs to a hexagonal system and has two types of crystal plane with different atomic arrangements: positively charged calcium ions are mainly present in the a(b)-planes, while negatively charged phosphate ions and hydroxyl groups are mainly present in the c-planes. In vertebrate long bone surfaces, HAp crystals have a c-axis orientation, which leads to the development of the a(b)-plane; while in tooth enamel surfaces, they have an a(b)-axis orientation, which leads to the development of the c-plane. However, it is not clear why the orientations of long bone and tooth enamel are in different crystal planes. In order to clarify this question, we have synthesized single-crystal apatite particles with preferred orientation to the a- and c-axes as models for bone and teeth enamel. This review first describes the syntheses process of single-crystal apatite particles with preferred orientation to a(b)- and c-axes and then discusses specific protein adsorption to the crystal surface of the resulting plate- and fiber-shaped apatite particles with different surface charges. In addition, porous apatite-fiber scaffolds (AFSs) fabricated using the fiber-shaped apatite particles and their application to tissue engineering of bone are described on the basis of the three-dimensional cell culture of mesenchymal stem cells derived from rat bone marrow using the AFS settled into a radial-flow bioreactor.

https://www.jstage.jst.go.jp/article/bpb/36/11/36_b13-00439/_pdf

Syntheses of single-crystal apatite particles with preferred orientation to the a- and c-axes as models of hard tissue and their applications.

In situ recellularization of the liver decellularized scaffold is a potential therapeutic alternative for liver transplantation. We aimed to develop an in situ procedure for recellularization of the rat liver using sodium lauryl ether sulfate (SLES) compared with Triton X-100/SDS. Rat liver specimens were rinsed with PBS, decellularized with either Triton X-100/SDS or SLES, and finally rinsed by distilled water. The efficiency of decellularized liver scaffolds was evaluated by histological, confocal Raman microscopy, histochemical staining, and DNA quantification assessments. Finally, in vivo studies were done to assess the biocompatibility of the liver scaffold by serum biochemical parameters and the recellularization capacity by histological and immunohistochemistry staining. Findings confirmed the preservation of extracellular matrix (ECM) components such as reticular, collagen, glycosaminoglycans, and neutral carbohydrates in both Triton X-100/SDS- and SLES-treated livers. Hoechst, feulgen, Hematoxylin and eosin, and DNA quantification assessments confirmed complete genetic content removal. The serological parameters showed no adverse impact on the liver functions. Transplantation of SLES-treated cell-free decellularized liver showed extensive neovascularization along with migration of the fibrocytes and adipocytes and some immune cells. Also, immunohistochemical staining showed that the oval cells, stellate cells, cholangiocytes and hepatocytes invaded extensively into the graft. It is concluded that SLES can be considered as a promising alternative in the liver decellularization process, and the transplanted decellularized liver can appropriately be revascularized and regenerated.

Decellularized liver transplant could be recellularized in rat partial hepatectomy model

Liver organoids were reconstructed by mouse-immortalized hepatocytes and nonparenchymal cells (sinusoidal endothelial cells and hepatic stellate cells) in a radial-flow bioreactor (RFB) A biodegradable apatite-fiber scaffold (AFS) was used as a scaffold packed in the RFB, which enables three-dimensional cell cultures The organoids cocultured in the RFB showed a liver-like structure with high-density layers of hepatocytes and the formation of vessel-like structures A liver organoid consisting of three cocultured cells was transplanted under the kidney capsule (kidney group) or into the omentum (omentum group) using BALB/c nude mice Transplanted liver organoids survived in the kidney or omentum The expression of mRNAs of albumin, connexin 26 and 32, hepatocyte nuclear factor 4α, and glucose-6-phosphatase was increased in both groups at 8 weeks after transplantation in comparison to the pretransplant status Tyrosine aminotransferase appeared only in the omentum group The results suggested that the functions of liver organoids differed depending on the transplanted site in the recipient animals

Transplantation of Liver Organoids in the Omentum and Kidney

Bone grafting is necessary before dental implant treatment in patients with jaw bone defects. Currently, autologous bone grafting is a major burden on the patient. However, it is impossible to form a sufficient foundation for the implant with a bone-filling agent alone. It is, therefore, necessary to prepare hybrid artificial bone tissue containing osteoblasts and osteoclasts. In this study, mouse MC3T3-E1 pre-osteoblast cells and human embryonic-derived osteoblastic cell line hFOB1.19 were cultured in radial-flow bioreactors (RFB) to form three-dimensional artificial bone filled with porous beads of β-tricalcium phosphate (β-TCP) or hydroxyapatite (HA)—which are clinically used as bone-filling agents—as cell culture carriers. When circulation culturing was performed in the growth medium for the first 10–12 days, glucose consumption was increased in the cultures with HA beads in comparison to the cultures with β-TCP beads. When cultured in the differentiation culture medium during the second half of the culture period, the glucose consumption decreased in the culture with HA beads. A DNA microarray analysis suggested that osteogenesis progressed fast in three-dimensional culture filled with HA beads and that partly differentiation into osteoblasts was prominent in cultures with β-TCP beads. In the growth process of MC3T3-E1 cells, the vitamin A metabolism was also activated, the synthesis and degradation of retinoic acid was enhanced, and the metabolism of the same process decreased at the end of differentiation in three-dimensional cultures. Three-dimensional circulation culture in RFB is considered to be useful for the formation of hybrid bio-artificial bone tissue.

/pdf/bio-artificial-bone-formation-model-with-a-radial-flow-1th3albdyk.pdf

Bio-artificial bone formation model with a radial-flow bioreactor for implant therapy-comparison between two cell culture carriers: porous hydroxyapatite and β-tricalcium phosphate beads.

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Transplantation of Liver Organoids in the Omentum and Kidney

Bio-artificial bone formation model with a radial-flow bioreactor for implant therapy-comparison between two cell culture carriers: porous hydroxyapatite and β-tricalcium phosphate beads.