Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

OBJECTIVETo investigate the growth activity of osteoblast on a novel strontium incorporated calcium sulfate and make comparison with normal calcium sulfate material.

METHODSOsteoblast was inoculated on samples and cell proliferation was measured on the 1st, 3rd, 5th days, and the activities of ALP and osteocalcin were observed on the 5th day. And microcosmic morphology of osteoblast was observed by scanning electron microscopy(SEM).

RESULTSOsteoblast grows robustly on tested material. Cell quantity on the surface of novel material was obviously higher than normal calcium sulfate material (P < 0.05). The activity of ALP and osteocalcin on novel material was 57.8% and 40.2% higher than on normal calcium sulfate material respectively (P < 0.05). On strontium incorporated surface, osteoblast spread well. Cells were polygonal with abundant cytoplasm and the morphology was active.

CONCLUSIONStrontium incorporated calcium sulfate can sustain robust growth activity of osteoblast, which is promising to be used for bone substitute materials.

3T3 Cells ; Alkaline Phosphatase ; metabolism ; Animals ; Bone Substitutes ; chemistry ; pharmacology ; Calcium Sulfate ; chemistry ; pharmacology ; Cell Proliferation ; drug effects ; Mice ; Osteoblasts ; cytology ; drug effects ; metabolism ; Osteocalcin ; metabolism ; Strontium ; chemistry

Quite a few orthopedics experts have fabricated some novel bone scaffolds with nanotechnology and have carried out some researches on nano-biological effects. The study of the biological effects about nano-biomaterials can facilitate the understanding of the interaction between the biomaterials and the organism, and provide research ideas and direction to construct new biomaterials with physiological function. To better understand the interaction of nano biomaterials with protein, cells and bio-security, this review presents recent advances of biological effects about nano scaffold for bone tissue engineering.
Biocompatible Materials ; metabolism ; Bone Substitutes ; Bone and Bones ; Humans ; Nanostructures ; Nanotechnology ; Surface Properties ; Tissue Engineering ; methods ; Tissue Scaffolds

This research sought to asses the efficacity of a new type of tissue engineering bone developed by PDLLA/ PLA-PEG-PLA and BMP as a kind of bone graft substitute in the rabbit model of mandibular defects; 15 mm x 6 mm bilateral mandibular periosteum bone defects were made surgically in 20 New Zealand adult rabbits. The porous scaffolds impregnated with rhBMP-2 were used for the purpose, and the scaffolds without rhBMP-2 were used as control. The methods adopted in this research were: macroscopy, histomorphologic exam, X-ray exam, SEM micrography, computer-aided analysis and graphics. The experimental group was shown to have an earlier inception of bone forming. New bone formation was seen along the border of the original mandibular bone and in the middle. At 12 weeks after surgery,the defects were almost filled with new bone. In the control group, the defects could not be repaired in its entirety, and there was no new bone in the middle. The porous scaffold is a promising carrier for BMP. This kind of bone graft substitute can serve as an osteoconductive and osteoinductive matrix.
Animals ; Bone Morphogenetic Protein 2 ; administration & dosage ; Bone Substitutes ; metabolism ; Female ; Implants, Experimental ; Lactic Acid ; administration & dosage ; Male ; Mandibular Injuries ; surgery ; Osteogenesis ; Polyesters ; administration & dosage ; Polyethylene Glycols ; administration & dosage ; Polymers ; administration & dosage ; Rabbits ; Recombinant Proteins ; administration & dosage ; Tissue Engineering ; Tissue Scaffolds

The RGD-containing peptide was used to modify the surface of porous PLGA-[ASP-PEG], and was incubated in the modified simulated body fluid (mSBF) for two weeks. The mineralization of PLGA-[ASP-PEG] was explored. The active peptide was used to modify PLGA-[ASP-PEG] through cross-linker (Sulfo-LC-SPDP), characterized by X-ray photoelectron spectroscopy (XPS) the peptide-modified PLGA-[ASP-PEG] (Experiment group, EG) and PLGA-[ASP-PEG] without modification (Control group, CG) were all incubated in mSBF for two weeks, confirmed by observation of Scanning electron microscope(SEM) and measurements of Energy dispersive analysis system of X-ray (EDS) and X-ray diffractometry (XRD). XPS indicated that the binding energy of sulphur in EG was 164eV, and the ratio of carbon to sulphur in EG was 99.746 : 0.1014, however, sulphur was not detected in CG; SEM analysis demonstrated that the mineralization layers were more consecutive and compact in EG than in CG. The results of EDS and XRD indicated that the main component of mineral was hydroxyapatite, and the ratio of Ca/P was 1.60 in EG, and 1.52 in CG. RGD-containing peptide provided enough functional groups for mineralization; the mineralized peptide- modified PLGA-[ASP-PEG] possessed the bonelike microstructure.
Biocompatible Materials ; chemistry ; Bone Substitutes ; Bone and Bones ; metabolism ; Calcification, Physiologic ; Lactic Acid ; chemistry ; Oligopeptides ; chemistry ; Osteogenesis ; drug effects ; Peptides ; chemical synthesis ; pharmacology ; Polyglycolic Acid ; chemistry ; Surface Properties

Magnesium is a macroelement which is indispensable to human bodies. As a lightweight metal with high specific strength and favorable biocompatibility, magnesium and its alloys have been introduced in the field of biomedical materials research and have a broad application prospect. It is possible to develop new type of biodegradable medical magnesium alloys by use of the poor corrosion resistance of magnesium. Bioabsorbable magnesium stents implanted in vivo could mechanically support the vessel in a short term, effectly prevent the acute coronary occlusion and in-stent restenosis, and then be gradully biodegraded and completely absorbed in a long term. Osteoconductive bioactivity in magnesium-based alloys could promote the apposition growth of bone tissue. This paper reviews the progress of magnesium and its alloys applied in bone tissue and cardiovascular stents, and the prospect of the future research of magnesium-based biomaterials is discussed.
Absorbable Implants ; Alloys ; chemistry ; metabolism ; Biocompatible Materials ; chemistry ; Bone Substitutes ; chemistry ; metabolism ; Humans ; Magnesium ; chemistry ; metabolism ; Stents

Magnesium is an essential microelement which is not harmful to human body. As a light-weight metal with properties similar to natural bone, magnesium material possesses the characteristics of its degradability, little biotoxicity, as well as its regulatory strength and controllable degradation-speed. After the tissue has healed sufficiently, the burden of a second surgical procedure can be avoided. Therefore, there is need of investigation on the possible use of magnesium and its alloys as medical biomaterials, and the study of its bioactivity is the foundation of further application. This article reviews the bioactivity of magnesium and its alloys.
Absorbable Implants ; Alloys ; chemistry ; metabolism ; Biocompatible Materials ; chemistry ; Bone Substitutes ; chemistry ; metabolism ; Humans ; Magnesium ; chemistry ; metabolism ; Prostheses and Implants

Compound membranes of chitosan/hydroxyapatite were prepared by blending. The physical performance showed that the air-water contact angles decreased from chitosan's 103 degrees to chitosan/hydroxyapatite's 57 and the water adsorption rate increased slightly. When immersed into culture medium, the materials adsorbed Ca2+, and low crystalline hydroxyapatite deposited on the surface of the membranes. Chitosan/hydroxyapatite compound membranes could enhance the attachment and proliferation of mescenchymal stem cells (MSCs). After 12 days' induction on the materials, the alkaline phosphatase (ALP) activity value of MSCs on the compound membrane was 10.1, being much higher than 1.6 on chitosan membrane (P<0.01). All these results indicate that chitosan does not have very good affinity for MSCs, but the biocompatibility of chitosan can be apparently enhanced after mixing with hydroxyapatite. The compound membrane stimulates MSCs to differentiate into osteoblasts and it may be a good potential material for bone substitution.
Alkaline Phosphatase ; metabolism ; Animals ; Bone Substitutes ; pharmacology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Chitosan ; chemical synthesis ; pharmacology ; Durapatite ; chemical synthesis ; pharmacology ; Membranes, Artificial ; Mesenchymal Stromal Cells ; cytology ; Rats

This study was performed to evaluate the osteogenic effect of allogenic canine umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) mixed with beta-tricalcium phosphate (beta-TCP) in orthotopic implantation. Seven hundred milligrams of beta-TCP mixed with 1 x 10(6) UCB-MSCs diluted with 0.5 ml of saline (group CM) and mixed with the same volume of saline as control (group C) were implanted into a 1.5 cm diaphyseal defect and wrapped with PLGC membrane in the radius of Beagle dogs. Radiographs of the antebrachium were made after surgery. The implants were harvested 12 weeks after implantation and specimens were stained with H&E, toluidine blue and Villanueva-Goldner stains for histological examination and histomorphometric analysis of new bone formation. Additionally, UCB-MSCs were applied to a dog with non-union fracture. Radiographically, continuity between implant and host bone was evident at only one of six interfaces in group C by 12 weeks, but in three of six interfaces in group CM. Radiolucency was found only near the bone end in group C at 12 weeks after implantation, but in the entire graft in group CM. Histologically, bone formation was observed around beta-TCP in longitudinal sections of implant in both groups. Histomorphometric analysis revealed significantly increased new bone formation in group CM at 12 weeks after implantation (p < 0.05). When applied to the non-union fracture, fracture healing was identified by 6 weeks after injection of UCB-MSCs. The present study indicates that a mixture of UCB-MSCs and beta-TCP is a promising osteogenic material for repairing bone defects.
Animals ; Biocompatible Materials/metabolism/therapeutic use ; Bone Substitutes/*therapeutic use ; Calcium Phosphates/*therapeutic use ; Dogs ; Fetal Blood/*cytology ; Fracture Fixation/methods/veterinary ; Mesenchymal Stem Cells/*physiology ; Osteogenesis/*physiology ; Tissue Engineering/methods ; Wound Healing/physiology

This study was aimed to compare the expression of BMP4 mRNA in the in-vivo tissue engineering bone constructed with Ca/P ceramics against the expression of BMP4 mRNA in the naturally healing bone. 20 porous Ca/P ceramics cylinders with Phi 5 mm x 8 mm were made and implanted into the dorsal muscles of 5 dogs. As control, one molar tooth was pulled out from each dog to create bone defect for the naturally healing bone at the same time. The specimens and the naturally healing bone were harvested at 1, 2, 4, 12 and 24 weeks post-implantation. After RNA extraction and reverse transcription, bone morphogenetic protein 4 (BMP4) and GAPDH mRNA were detected by real-time quantitative polymerase chain reaction (PCR) method. The results showed that the expression level of BMP4 mRNA of the in-vivo tissue engineering bone constructed with Ca/P ceramics was higher than that of the naturally healing bone in the period of experiment. However, the in-vivo tissue engineering bone had the same chronological order of BMP mRNA expression that the naturally healing bone did. As a bone substitute analogous to autologous bone, the in-vivo tissue engineering bone constructed with Ca/P ceramics has the potential for clinical application.
Animals ; Bone Morphogenetic Protein 4 ; genetics ; metabolism ; Bone Substitutes ; chemistry ; Calcium Phosphates ; chemistry ; Ceramics ; chemistry ; Dogs ; Humans ; Implants, Experimental ; RNA, Messenger ; genetics ; metabolism ; Tissue Engineering