Yuchen Guo

A Novel Nanosilver/Nanosilica Hydrogel for Bone Regeneration in Infected Bone Defects

Treating bone defects in the presence of infection is a formidable clinical challenge. The use of a biomaterial with the dual function of bone regeneration and infection control is a novel therapeutic approach to this problem. In this study, we fabricated an innovative, dual-function biocomposite hydrogel containing nanosilver and nanosilica (nAg/nSiO2) particles and evaluated its characteristics using FT-IR, SEM, swelling ratio, and stiffness assays. The in vitro antibacterial analysis showed that this nAg/nSiO2 hydrogel inhibited both Gram-positive and Gram-negative bacteria. In addition, this nontoxic material could promote osteogenic differentiation of rat bone marrow stromal cells (BMSCs). We then created infected bone defects in rat calvaria in order to evaluate the function of the hydrogel in vivo. The hydrogel demonstrated effective antibacterial ability while promoting bone regeneration in these defects. Our results indicate that this nAg/nSiO2 hydrogel has the potential to both control infection and to promote bone healing in contaminated defects.

FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice

Chronic kidney disease (CKD) is a worldwide health problem. Serum levels of FGF23, a phosphaturic hormone, increase at the earliest stages of CKD, and have been found to be independently associated with the mortality and morbidity of CKD patients. The purpose of this study was to evaluate whether FGF23 neutralization was able to improve bone quality and osseointegration of titanium implants. Uremia was induced by 5/6 nephrectomy in adult female mice. Postsurgery, the mice were injected with vehicle or FGF23 neutralizing antibody (5 mg/kg body weight) 3 times a week. Experimental titanium implants were inserted in the distal end of the femurs. FGF23 neutralization significantly increased serum phosphate, 1,25(OH)2D and BUN, and decreased serum PTH and FGF23, relative to vehicle-treated CKD mice. Histomorphometric analysis of the tibiae indicated that FGF23 neutralization normalized the osteoidosis observed in vehicle-treated CKD mice. Although bone-implant contact ratio remained unchanged by anti-FGF23 antibody treatment, the strength of osseointegration, as evidenced by a biomechanical push-in test, was significantly improved by FGF23 neutralization. Our findings revealed that FGF23 neutralization effectively improves bone quality and osseointegration of titanium implants in CKD mice, suggesting FGF23 as a key factor of CKD related bone diseases.

Evaluation of periodontitis and bone loss in patients undergoing hemodialysis.

BACKGROUND Chronic kidney disease has been a worldwide public health challenge and also a risk factor for oral health. The objectives of this study are to investigate the periodontal status in Chinese patients undergoing hemodialysis (HD) and assess periodontal bone loss (BL) using cone-beam computerized tomography (CBCT). METHODS The patients in the HD and control groups received periodontal and CBCT examinations in the same period. Age, sex, and HD details were obtained from a hospital database. Periodontal status was evaluated using the community periodontal index (CPI) and clinical attachment loss (AL). Periodontal BL was measured by the distance from the cemento-enamel junction to the alveolar crest using CBCT. The distance between the furcation upper and lower boundaries was considered the furcation defect. RESULTS One hundred two patients undergoing HD and 204 control patients were enrolled. As for the demographic data and number of remaining teeth for each patient, there was no significant difference between HD and control groups. The CPI and AL showed statistical differences (P <0.001). The results of periodontal BL indicated that the patients undergoing HD had significantly more BL at their mandibular first premolars and first molars than did patients in the control group (P <0.01) at every site except the disto-buccal one (P <0.05). As for the furcation defects, the distance for the patients undergoing HD was nearly double that of the patients in the control group (P <0.001). CONCLUSION Compared with the generally healthy population, periodontitis and periodontal BL were significantly more severe in the Chinese patients undergoing HD.

Effect of estrogen deficiency on the fixation of titanium implants in chronic kidney disease mice

SummaryWe established a chronic kidney disease (CKD) mouse model with estrogen deficiency and inserted titanium implants into the femur of such mice to investigate the fixation of the implants. Both the histomorphometry and implant resistance indicated that estrogen deficiency impaired the fixation of titanium implants inserted into such mice.IntroductionCKD has been regarded as a worldwide public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. A previous study demonstrated that CKD impairs the early healing of titanium implants. However, the combined effect of estrogen deficiency and CKD on the fixation of titanium implants is largely unknown.MethodsForty 9-week-old female C57BL mice were randomly divided into sham, ovariectomy (OVX), CKD, and CKD + OVX groups. Uremia and estrogen deficiency were induced by 5/6 nephrectomy and OVX, respectively. Experimental titanium implants were inserted into the distal end of the femur. Bone-implant contact (BIC) ratio and bone volume (BV/TV) around the implants were histomorphometrically analyzed. The fixation strength of the implant was measured by a biomechanical push-in resistance test.ResultsSerum measurement confirmed a significant increase in serum blood urea nitrogen (BUN) in the CKD group, which was further increased by OVX. Estrogen deficiency led to significant decreases in the BIC ratio, BV/TV, and the push-in resistance in CKD animals. There was a significant interaction between the effects of OVX and CKD, with OVX exacerbating the effects of CKD on BIC ratio and push-in resistance.ConclusionsThe results indicated that estrogen deficiency exerts a synergistic effect with CKD and further impairs the fixation of titanium implants in CKD mice.

Estrogen Deficiency Leads to Further Bone Loss in the Mandible of CKD Mice

Background Chronic kidney disease (CKD) has been regarded as a grave public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. Our previous study demonstrated that CKD impairs the healing of titanium implants. The aim of this study was to investigate the effects of estrogen deficiency on the mandibular bone in CKD mice. Methods Forty eleven-week-old female C57BL mice were used in this study. Uremia and estrogen deficiency were induced by 5/6 nephrectomy and ovariectomy (OVX), respectively. After 8 weeks, the mice were sacrificed, and their mandibles were collected for micro-CT analysis and histological examination. Results All the mice survived the experimental period. Serum measurements confirmed a significant increase in BUN in the CKD group that was further increased by OVX. OVX led to significant decreases in both the BV/TV and cortical thickness of the mandibular bone in CKD mice. Conclusion In summary, our findings indicate that estrogen deficiency leads to further mandibular bone loss in CKD mice.

Effect of Resorbable Collagen Plug on Bone Regeneration in Rat Critical-Size Defect Model.

Objective:The purpose of this investigation was to examine the effect of resorbable collagen plug (RCP) on bone regeneration in rat calvarial critical-size defects. Methods:About 5-mm-diameter calvarial defects were created in forty 12-week-old male Sprague-Dawley rats and implanted with or without RCP. Animals were killed at 1, 2, 4, and 8 weeks postoperatively. After being killed, specimens were collected and subjected to micro-computed tomography (&mgr;CT) and histological analysis. Results:The &mgr;CT showed a significant increase of newly formed bone volume/tissue volume in RCP-implanted defect compared with controls at all designated time points. After 8 weeks, the defects implanted with RCP displayed almost complete closure. Hematoxylin and eosin staining of the decalcified sections confirmed these observations and evidenced active bone regeneration in the RCP group. In addition, Massons trichrome staining demonstrated that RCP implantation accelerated the process of collagen maturation. Conclusions:The RCP enhances bone regeneration in rat critical-size cranial defects, which suggest it might be a desired material for bone defect repair.

Effect of gelatin sponge with colloid silver on bone healing in infected cranial defects

Oral infectious diseases may lead to bone loss, which makes it difficult to achieve satisfactory restoration. The rise of multidrug resistant bacteria has put forward severe challenges to the use of antibiotics. Silver (Ag) has long been known as a strong antibacterial agent. In clinic, gelatin sponge with colloid silver is used to reduce tooth extraction complication. To investigate how this material affect infected bone defects, methicillin-resistant Staphylococcus aureus (MRSA) infected 3-mm-diameter cranial defects were created in adult female Sprague-Dawley rats. One week after infection, the defects were debrided of all nonviable tissue and then implanted with gelatin sponge with colloid silver (gelatin/Ag group) or gelatin alone (gelatin group). At 2 and 3days after debridement, significantly lower mRNA expression levels of IL-6 and TNF-α and lower plate colony count value were detected in gelatin/Ag group than control. Micro-CT analysis showed a significant increase of newly formed bone volume fraction (BV/TV) in gelatin/Ag treated defects. The HE stained cranium sections also showed a faster rate of defect closure in gelatin/Ag group than control. These findings demonstrated that gelatin sponge with colloid silver can effectively reduce the infection caused by MRSA in cranial defects and accelerate bone healing process.

Marginal bone loss around non-submerged implants is associated with salivary microbiome during bone healing

Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss. Saliva samples were collected from all subjected and were analysed using 16S MiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing.

Ubiquitin‐specific protease USP34 controls osteogenic differentiation and bone formation by regulating BMP2 signaling

The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin‐dependent protein degradation is critical for the differentiation of MSCs and bone formation; however, the function of ubiquitin‐specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre‐osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2‐induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34‐deficient MSCs in vitro. Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.

Deubiquitinating Enzymes and Bone Remodeling

Bone remodeling, which is essential for bone homeostasis, is controlled by multiple factors and mechanisms. In the past few years, studies have emphasized the role of the ubiquitin-dependent proteolysis system in regulating bone remodeling. Deubiquitinases, which are grouped into five families, remove ubiquitin from target proteins and are involved in several cell functions. Importantly, a number of deubiquitinases mediate bone remodeling through regulating differentiation and/or function of osteoblast and osteoclasts. In this review, we review the functions and mechanisms of deubiquitinases in mediating bone remodeling.