In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration.

Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

Influence of P(VDF-TrFE) Membranes with Different Surface Potentials on the Activity and Angiogenic Function of Human Umbilical Vein Endothelial Cells.

During bone tissue regeneration, neovascularization is critical, and the formation of a blood supply network is crucial for bone growth stimulation and remodeling. Previous studies suggest that bioelectric signals facilitate the process of angiogenesis. Owing to their biomimetic electroactivity, piezoelectric membranes have garnered substantial interest in the field of guided bone regeneration. Nevertheless, the knowledge of their influence due to varying surface potentials on the progression of angiogenesis remains ambiguous. Therefore, we proposed the preparation of an electroactive material, P(VDF-TrFE), and investigated its effects on the activity and angiogenic functions of human umbilical vein endothelial cells (HUVECs). The HUVECs were directly cultured on P(VDF-TrFE) membranes with different surface potentials. Subsequently, cell viability, proliferation, migration, tube formation, and expressions of related factors were assessed through appropriate assays. Our results revealed that the negative surface potential groups exerted differential effects on the modulation of angiogenesis in vitro. The P(VDF-TrFE) membranes with negative surface potential exhibited the greatest effect on cellular behaviors, including proliferation, migration, tube formation, and promotion of angiogenesis by releasing key factors such as VEGF-A and CD31. Overall, these results indicated that the surface potential of piezoelectric P(VDF-TrFE) membranes could exert differential effects on angiogenesis in vitro. We present a novel approach for designing bioactive materials for guided bone regeneration.

Janus electro-microenvironment membrane with surface-selective osteogenesis/gingival healing ability for guided bone regeneration.

Guided bone regeneration is widely applied in clinical practice to treat alveolar bone defects. However, the rate of healing of severe alveolar bone defects is slow, and there is a high incidence of soft tissue wound dehiscence. In this study, we propose a barrier membrane with a Janus electro-microenvironment (JEM) to achieve side-selective bone regeneration and soft tissue healing. The JEM membrane was constructed using a polarized polyvinylidene fluoride ferroelectric membrane with different surface potentials on either side. It promoted osteogenic differentiation and bone regeneration on the negatively polarized side (JEM-) and soft tissue regeneration on the positively polarized side (JEM+). Further investigation revealed that the JEM-mediated promotion of bone formation was related to mitochondrial autophagy, as indicated by depolarization of the mitochondrial membrane potential and the expression of LC3, Pink I, and Parkin. Moreover, the gingival healing promoted by JEM+ was related to oxidative phosphorylation in mitochondria, as indicated by the upregulation of mitochondrial complexes I-V and an increase in ATP generation. The design concept of the JEM provides a new avenue for regulating tissue regeneration between different tissue interfaces.

Local delivery of rhVEGF165 through biocoated nHA/coral block grafts in critical-sized dog mandible defects: a histological study at the early stages of bone healing.

Alveolar defects of a critical size cannot heal completely without grafting. Thus, they represent a major clinical challenge to reconstructive surgery. Numerous types of grafts have been used to improve bone regeneration. In the case of particle grafts, the capacity for volume rebuilding and space maintaining is still not ideal, particularly for critical-sized bone defects. Although porous block grafts can overcome the above problems of particle grafts, they are still not widely used for critical-sized alveolar defects, because of their reduced efficacy in blood vessel and bone formation. Thus, in the present study, nano-hydroxyapatite/coralline (nHA/coral) blocks were pre-vascularized by coating them with vascular endothelial growth factor (VEGF), and then implanted in dogs with critical-sized mandibular defects. This model has possible applications in orthopedic and implant surgery. In vivo results indicate that the nHA/coral blocks allow cell and collagen ingrowth because of their suitable pore size and interconnectivity of pores. In addition, pre-vascularization properties were obtained by coating the scaffolds with VEGF. Histological and immunohistochemical examinations, as well as fluorescence analysis, revealed that the local delivery of VEGF can significantly improve neovascularization and mineralization of newly formed bone at the early stages of bone healing in this dog implantation model. Our data collectively show that nHA/coral blocks have possible applications in bone tissue engineering, and excellent results can be achieved by pre-vascularization with VEGF.

Phosphoric acid and sodium fluoride: a novel etching combination on titanium.

We investigate whether a novel and inexpensive etching method, H3PO4 + NaF, on titanium could obtain both a lower hydrogen content and superior calcium phosphate deposition performance, while achieving similar surface roughness in comparison with the traditional etching method. Pure titanium samples were treated with different concentrations of H3PO4 + NaF at ambient temperature without auxiliary implementations (groups A, B and C), and were treated using the traditional method (group T). The samples were then maintained in simulated body fluid for 10 and 20 days. The surface morphology and chemistry, as well as the hydrogen content and distribution, were studied. The hydrogen content of the new groups are in the range of 31 (3.6)-86.9 (7.2) ppm, and that of group T is 287 (13.5) ppm. The amount of deposited calcium phosphates increases as the hydrogen content approaches 90 ppm; however, this trend does not apply as the hydrogen content exceeds 90 ppm. The surface roughnesses of groups A, B and C are in the range of 0.47 (0.01)-0.92 (0.05) µm. The new surface topography regularly transforms, and the surfaces with round pits exert a better effect on the deposition of calcium phosphates than the surfaces with sharp cusps.

Use of a collagen membrane loaded with recombinant human bone morphogenetic protein-2 with collagen-binding domain for vertical guided bone regeneration.

BACKGROUND: Vertical bone regeneration of severe atrophic alveolar ridges remains a challenging procedure in implant dentistry. METHODS: The aim of this study, accordingly, is to use a rabbit vertical guided bone regeneration model to evaluate whether using a collagen membrane (CM) loaded with small doses of recombinant human bone morphogenetic protein-2 with collagen-binding domain (rhBMP-2/CBD) would enhance two-way vertical bone regeneration. In each of eight rabbits, four titanium cylinders were screwed in perforated slits made into the external cortical bones of the calvaria. The following four treatment modalities were randomly allocated: 1) cylinders filled with mineralized bone matrix and covered with CM/rhBMP-2/CBD; 2) cylinders filled with mineralized bone matrix and covered with CM/rhBMP-2; 3) cylinders filled with mineralized bone matrix and covered with CM alone; or 4) cylinders filled with mineralized bone matrix without a membrane cover. RESULTS: After 6 weeks, the new bones were examined by histologic analysis. Slender new bone trabeculae were observed in the superficial layer of the titanium cylinders covered with CM/rhBMP-2/CBD, and higher degrees of bone were observed in this group compared with the other three groups. The average area fraction of newly formed bone was significantly more in the CM/rhBMP-2/CBD group compared with the CM/rhBMP-2, CM, or the no membrane control groups (all P <0.01). CONCLUSIONS: The present study demonstrates that CMs loaded with small doses of rhBMP-2/CBD induce new bone formation not only from the surface of the native bone, but also from the superficial structures. The augmented new bone, therefore, is improved in both quantity and quality.

The effects of different wavelength UV photofunctionalization on micro-arc oxidized titanium.

Many challenges exist in improving early osseointegration, one of the most critical factors in the long-term clinical success of dental implants. Recently, ultraviolet (UV) light-mediated photofunctionalization of titanium as a new potential surface treatment has aroused great interest. This study examines the bioactivity of titanium surfaces treated with UV light of different wavelengths and the underlying associated mechanism. Micro-arc oxidation (MAO) titanium samples were pretreated with UVA light (peak wavelength of 360 nm) or UVC light (peak wavelength of 250 nm) for up to 24 h. UVC treatment promoted the attachment, spread, proliferation and differentiation of MG-63 osteoblast-like cells on the titanium surface, as well as the capacity for apatite formation in simulated body fluid (SBF). These biological influences were not observed after UVA treatment, apart from a weaker effect on apatite formation. The enhanced bioactivity was substantially correlated with the amount of Ti-OH groups, which play an important role in improving the hydrophilicity, along with the removal of hydrocarbons on the titanium surface. Our results showed that both UVA and UVC irradiation altered the chemical properties of the titanium surface without sacrificing its excellent physical characteristics, suggesting that this technology has extensive potential applications and merits further investigation.