Application of computer-aided design and 3D-printed template for accurate bone augmentation in the aesthetic region of anterior teeth.

PURPOSE: To explore the outcomes of bone augmentation in the aesthetic zone of the anterior teeth using computer-aided design and a 3D-printed template. METHODS: Ten patients with severe bone defects in the aesthetic zone of anterior teeth were included in the study; CT data were collected before surgery. The design of the osteotomy line in the bone defect area was determined under computer simulation. The position parameters and osteotomy line of the free bone were determined via virtual surgery. A 3D-printed template was prepared to guide the accurate placement of the bone graft. Reexamination was conducted to evaluate the position of the bone graft immediately after the operation and the resorbed capacity of the bone graft before implant restoration. RESULTS: The position of the bone graft was consistent with the preoperative design. The amount of bone graft resorbed was within the acceptable range three months after the operation, and the effect of implant restoration was satisfactory. CLINICAL SIGNIFICANCE: Use of computer-aided design and a 3D-printed template can be an effective approach for accurate bone augmentation in the aesthetic zone of the anterior teeth.

A nano-targeted co-delivery system based on gene regulation and molecular blocking strategy for synergistic enhancement of platinum chemotherapy sensitivity in ovarian cancer.

Ovarian cancer (OC) has a low five-year survival rate, mainly because of its drug resistance to chemotherapy. It is the key to reverse drug resistance to combine multiple sensitization pathways to play a synergistic role. A nano scaled targeted co-delivery system (P123-PEI-G12, PPG) modified by bifunctional peptide tLyP-1-NLS (G12) was fabricated by using Pluronic P123 conjugated with low molecular weight polyethyleneimine (PEI). This delivery system can co-delivery Olaparib (Ola) and p53 plasmids to synergistically enhance the sensitivity of OC to platinum-based chemotherapy. P53@P123-PEI-G2/Ola (Co-PPGs) can achieve efficient tumor accumulation and cellular internalization through G12-mediated targeting. Co-PPGs then break down in the tumor cells, releasing the drug. Co-PPGs significantly enhanced the sensitivity of cisplatin (DDP) in platinum-resistant ovarian cancer (PROC) and synergistically inhibited the proliferation of PROC in vitro and in vivo. The sensitizing and synergistic effects of Co-PPGs were related to the activation of p53, inhibition of poly-ADP-ribose polymerase (PARP) and p-glycoprotein (P-gp) expression. This work provides a promising strategy for the effective treatment of PROC.

Nano-composite hydrogels of Cu-Apa micelles for anti-vasculogenic mimicry.

Vasculogenic mimicry (VM) describes the phenomenon whereby fluid-conducting vessels are formed by highly invasive tumour cells, which supply blood to tumours during their early growth stages. Single antiangiogenic agents have limited inhibitory effects on VM, therefore, a multi-pathway anti-VM strategy is required. In this study, Apatinib (Apa) was coordinated with Cu2+ to form a Cu-Apa copper complex. The latter was loaded into oligo-hyaluronic acid (HA) polymeric micelles (HA-Chol) and subsequently embedded in Astragalus polysaccharide-based in situ hydrogels (APsGels) to generate Cu-Apa/HA-Chol@APsGels. In this system, Cu-Apa exerts the combined effects of Cu2+ and Apa to inhibit VM; HA-Chol micelles achieve targeted drug delivery and enhance endocytosis efficiency; APsGels realise sustained release of the drugs to ensure an anti-VM effect. This system demonstrated improved VM inhibition with low cytotoxicity and high biocompatibility, wound healing, and transwell invasion in three-dimensional cell cultured VM. Moreover, this system significantly inhibited VM formation and melanoma growth in a mouse tumour transplantation model. This study provides an effective strategy for inhibiting VM.

Marriage of High-Throughput Gradient Surface Generation With Statistical Learning for the Rational Design of Functionalized Biomaterials.

Functional biomaterial is already an important aspect in modern therapeutics; yet, the design of novel multi-functional biomaterial is still a challenging task nowadays. When several biofunctional components are present, the complexity that arises from their combinations and interactions will lead to tedious trial-and-error screening. In this work, a novel strategy of biomaterial rational design through the marriage of gradient surface generation with statistical learning is presented. Not only can parameter combinations be screened in a high-throughput fashion, but also the optimal conditions beyond the experimentally tested range can be extrapolated from the models. The power of the strategy is demonstrated in rationally designing an unprecedented ternary functionalized surface for orthopedic implant, with optimal osteogenic, angiogenic, and neurogenic activities, and its optimality and the best osteointegration promotion are confirmed in vitro and in vivo, respectively. The presented strategy is expected to open up new possibilities in the rational design of biomaterials.

Dynamic surface adapts to multiple service stages by orchestrating responsive polymers and functional peptides.

Control over the implant surface functions is highly desirable to enhance tissue healing outcomes but has remained unexplored to adapt to the different service stages. In the present study, we develop a smart titanium surface by orchestrating thermoresponsive polymer and antimicrobial peptide to enable dynamic adaptation to the implantation stage, normal physiological stage and bacterial infection stage. The optimized surface inhibited bacterial adhesion and biofilm formation during surgical implantation, while promoted osteogenesis in the physiological stage. The further temperature increase driven by bacterial infection induced polymer chain collapse to expose antimicrobial peptides by rupturing bacterial membranes, as well as protect the adhered cells from the hostile environment of infection and abnormal temperature. The engineered surface could inhibit infection and promote tissue healing in rabbit subcutaneous and bone defect infection models. This strategy enables the possibility to create a versatile surface platform to balance bacteria/cell-biomaterial interactions at different service stages of implants that has not been achieved before.

Mitochondrial targeted hierarchical drug delivery system based on HA-modified liposomes for cancer therapy.

Chemotherapy targeting mitochondrial is a faster and more sensitive anti-tumor therapy strategy. In this study, a hierarchical drug delivery system HA-GDT-Lip was constructed by coupling glycyrrhetinic acid (GA), triphenylphosphine (TPP), and doxorubicin (DOX), encapsulating them in cationic liposomes (CLs), then coating the surface of CLs with HA. HA-GDT-Lip nanoparticles can be accumulated in tumor tissue through the EPR effect, then achieve tumor cell-specific endocytosis mediated by the CD44 receptor, DOX can be successfully delivered into mitochondria through the combined action of GA and TPP. Physicochemical properties analysis showed that HA-GDT-Lip nanoparticles were uniform in size and spherical in shape. In vitro cell experiments showed that HA-GDT-Lip had high cell uptake efficiency and mitochondrial targeting ability. In addition, HA-GDT-Lip could induce MPTP opening and accelerate cell apoptosis. Meanwhile, HA-GDT-Lip showed excellent antitumor activity and in vivo safety in tumor-bearing nude mice. In conclusion, HA-GDT-Lip may serve as a promising mitochondrial delivery system to reduce the side effects of anticancer drugs and improve their antitumor efficacy.

Phragmites rhizoma polysaccharide-based nanocarriers for synergistic treatment of ulcerative colitis.

The purpose of this study was to construct Phragmites rhizoma polysaccharide-based nano-drug delivery systems (PRP2-SeNPs-H/Aza-Lips) for synergistically alleviating ulcerative colitis and to investigate the important roles of Phragmites rhizoma polysaccharide-based nanocarriers in PRP2-SeNPs-H/Aza-Lips. Phragmites rhizoma polysaccharide (PRP2) was isolated and used for the preparation of Phragmites rhizoma polysaccharide selenium nanoparticles with low selenium content (PRP2-SeNPs-L) and high selenium content (PRP2-SeNPs-H). Based on the electrostatic attraction between PRP2-SeNPs-H and azathioprine liposomes (Aza-Lips), PRP2-SeNPs-H/Aza-Lips were constructed for precise delivery of the model drug azathioprine (Aza) to colon lesions. Results showed that PRP2 significantly alleviated the clinical symptoms and colon tissue damage and down-regulated the levels of inflammatory factors in serum and colon, demonstrating beneficial effects on mice with ulcerative colitis. PRP2-SeNPs-L had better relieving effects on ulcerative colitis. Phragmites rhizoma polysaccharide-based nanocarriers may protect azathioprine liposomes against gastrointestinal digestion, enhance the therapeutic effects on ulcerative colitis, and significantly reduce liver damage from azathioprine, which helps to improve the efficacy and toxicity of clinical drugs.

High-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity.

Peptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.

Evaluating the performance of inorganic draw solution concentrations in an anaerobic forward osmosis membrane bioreactor for real municipal sewage treatment.

Sewage can become a valuable source if its treatment is re-oriented for recovery. An anaerobic forward osmosis membrane bioreactor (AnOMBR) was developed for real municipal sewage treatment to investigate performance, biogas production, flux change and mixed liquor characteristics. The AnOMBR had a good treatment capacity with removal ratio of chemical oxygen demand, ammonia nitrogen, total nitrogen and total phosphorus more than 96%, 88%, 89% and almost 100%. Although high DS concentration increased the initial flux, it caused rapid decline and poor recoverability of FO membrane flux. Low DS concentration led to too long hydraulic retention time, thus resulting in a low reactor efficiency. Additionally, it was observed that salt, protein, polysaccharide and humic acid were all accumulated in the reactor, which was not conducive to stable long-term operation. Based on the characteristics of membrane fouling, salt accumulation and AnOMBR performance, the optimal DS of 1 M NaCl solution was selected.

Conductive and antimicrobial macroporous nanocomposite hydrogels generated from air-in-water Pickering emulsions for neural stem cell differentiation and skin wound healing.

Electro-active conducting hydrogels have shown promising applications in promoting soft tissue regeneration. However, achieving good conductive performance while simultaneously imparting macroporous structures to these hydrogels still remains challenging. In this study, we report the development of multifunctional conductive macroporous nanocomposite hydrogels (MNHs) prepared by an air-in-water emulsion template that is stabilized by colloidal hybrids of carbon nanotubes (CNTs) and gelatin methacryloyl. The MNH hydrogels demonstrated tunable pore size, electrical conductivity and mechanical properties with various CNT concentrations in the crosslinking matrices. An in vitro cell assay showed that the MNH hydrogels could promote the spreading and differentiation of NE-4C neural stem cells. Furthermore, sustainable release of antimicrobial peptides (AMPs) from the MNH hydrogel can be achieved and the released AMPs maintained high S. aureus killing activity. An in vivo evaluation of the MNH hydrogel using a murine dorsal skin model further showed that the conductive MNH hydrogel loaded with AMPs demonstrated appealing antimicrobial and wound healing performance in two weeks.

Direct concentration of municipal sewage by forward osmosis and membrane fouling behavior.

Forward osmosis (FO) draws attention due to its advantages compares to traditional pressure-driven membrane processes. In this study, a FO membrane concentrating system was built for sewage concentration to investigate membrane rejection, concentrating effect, membrane fouling behavior. Sewage could be concentrated to 1/10 original volume by FO membrane, while pollutants concentrating multiple could not reach 10. The FO membrane had excellent rejecting effect, with effluent COD, ammonia nitrogen, total nitrogen, total phosphorus concentration of 18, 2.5, 2.8, 0.4mg/L, respectively. The FO membrane flux was mainly associated with the draw solution (DS) concentration, which increased with DS concentration but more severe membrane fouling engendered in the meantime. Scanning electronic microscope and fourier transform infrared spectroscopy analysis indicated the formation and constitution of the fouling layer, which included humic acid, protein, and polysaccharide. After concentration, fouled FO membrane was remitted by physical and chemical cleaning, with recovery of 90% and 96%.

Self-assembled three-dimensional double network graphene oxide/polyacrylic acid hybrid aerogel for removal of Cu2+ from aqueous solution.

Three-dimensional (3D) double network graphene oxide/polyacrylic acid (GO/PAA) hybrid aerogels were fabricated under mild conditions from the mixture of GO and acrylic acid (AA) monomers using a one-pot in situ solution polymerization process which included the polymerization of AA and the self-assembly of functional GO sheets. The PAA chains served as not only binder to assemble GO sheets into 3D framework but also modifier to provide more active functional groups. The adsorbents based on such material exhibited superior adsorption performance towards Cu2+ ions in aqueous media due to rich mesopores, high specific surface area, and abundant active sites. This work brings a new vision for assembling 3D porous graphene-based nanomaterials as adsorbents in environmental protection.

Temperature-Controlled Reversible Exposure and Hiding of Antimicrobial Peptides on an Implant for Killing Bacteria at Room Temperature and Improving Biocompatibility in Vivo.

Modification of implants by antimicrobial peptides (AMPs) can improve the antimicrobial activity of the implants. However, AMPs have some cytotoxicity in vivo when they are exposed at body temperature. To tackle this challenge, we propose to develop a new approach to generating a smart antimicrobial surface through exposure of AMPs on the surface. A polydopamine film was first formed on the substrates, followed by the conjugation of a temperature-sensitive polymer, poly( N-isopropylacrylamide) (pNIPAM), to the film through atom transfer radical polymerization (ATRP). Then, AMPs were conjugated to the NIPAM on the resultant pNIPAM-modified surface through a click chemistry reaction. Because of the temperature-sensitive property of pNIPAM, the AMPs motif was more exposed to the external environment at room temperature (25 °C) than at body temperature (37 °C), making the surface present a higher antimicrobial activity at room temperature than at body temperature. More importantly, such a smart behavior is accompanied with the increased biocompatibility of the surface at body temperature when compared to the substrates unmodified or modified by AMPs or pNIPAM alone. Our in vivo study further verified that pNIPAM-AMP dual modified bone implants showed increased biocompatibility even when they were challenged with the bacteria at room temperature before implantation. These results indicate that the implants are antibacterial at room temperature and can be safely employed during surgery, resulting in no infection after implantations. Our work represents a new promising strategy to fully explore the antimicrobial property of AMPs, while improving their biocompatibility in vivo. The higher exposure of AMPs at room temperature (the temperature for storing the implants before surgery) will help decrease the risk of bacterial infection, and the lower exposure of AMPs at body temperature (the temperature after the implants are placed into the body by surgery) will improve the biocompatibility of AMPs.

A comparative study of high-viscosity cement percutaneous vertebroplasty vs. low-viscosity cement percutaneous kyphoplasty for treatment of osteoporotic vertebral compression fractures.

The clinical effects of two different methods-high-viscosity cement percutaneous vertebroplasty (PVP) and low-viscosity cement percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCFs) were investigated. From June 2010 to August 2013, 98 cases of OVCFs were included in our study. Forty-six patients underwent high-viscosity PVP and 52 patients underwent low-viscosity PKP. The occurrence of cement leakage was observed. Pain relief and functional activity were evaluated using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), respectively. Restoration of the vertebral body height and angle of kyphosis were assessed by comparing preoperative and postoperative measurements of the anterior heights, middle heights and the kyphotic angle of the fractured vertebra. Nine out of the 54 vertebra bodies and 11 out of the 60 vertebra bodies were observed to have cement leakage in the high-viscosity PVP and low-viscosity PKP groups, respectively. The rate of cement leakage, correction of anterior vertebral height and kyphotic angles showed no significant differences between the two groups (P>0.05). Low-viscosity PKP had significant advantage in terms of the restoration of middle vertebral height as compared with the high-viscosity PVP (P<0.05). Both groups showed significant improvements in pain relief and functional capacity status after surgery (P<0.05). It was concluded that high-viscosity PVP and low-viscosity PKP have similar clinical effects in terms of the rate of cement leakage, restoration of the anterior vertebral body height, changes of kyphotic angles, functional activity, and pain relief. Low-viscosity PKP is better than high-viscosity PVP in restoring the height of the middle vertebra.

Improved mechanical properties of hydroxyapatite whisker-reinforced poly(L-lactic acid) scaffold by surface modification of hydroxyapatite.

To improve the mechanical properties of porous hydroxyapatite/poly(L-lactic acid) (HA/PLLA) composites, HA whiskers with high crystallinity and high aspect ratio were synthesized. HA whiskers were modified with γ-aminopropyltriethoxysilane (APTES) to improve the interface between HA whiskers and PLLA. The composite scaffold consists of a porous PLLA matrix with HA whiskers distributed homogeneously. The morphology and the distributions of pore sizes of PLLA scaffold was not influenced by introducing HA whiskers, while the mechanical properties were improved. Both the compressive strength and compressive modulus were increased with the weight ratio of APTES-modified HA whiskers up to 30 wt.%, but only up to 15 wt.% for non-modified HA whiskers. With more than 15 wt.% HA whiskers, the mechanical properties of HA/PLLA scaffold were better improved with APTES-modified HA whiskers than non-modified. The HA whisker/PLLA scaffold with high porosity and improved mechanical properties is attractive in the application of tissue engineering.

Hierarchical structure and cytocompatibility of fish scales from Carassius auratus.

To study the structure and the cytocompatibility of fish scales from Carassius auratus, scanning electron microscopy (SEM) was used to observe the morphology of fish scales treated with different processing methods. Based on varying morphologies and components, the fish scales can be divided into three regions on the surface and three layers in vertical. The functions of these three individual layers were analyzed. SEM results show that the primary inorganic components are spherical or cubic hydroxyapatite (HA) nanoparticles. The fish scales have an ~60° overlapped plywood structure of lamellas in the fibrillary plate. The plywood structure consists of co-aligned type I collagen fibers, which are parallel to the HA lamellas. X-ray diffraction (XRD), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC) and Fourier transform infrared (FTIR) analysis indicate that the main components are HA and type I collagen fibers. MC3T3-E1 cell culture results show a high cytocompatibility and the ability to guide cell proliferation and migration along the scale ridge channels of the fish scales. This plywood structure provides inspiration for a structure-enhanced composite material.

Large-diameter metal-on-metal cementless total hip arthroplasty in the elderly.

To evaluate the clinical effectiveness and complications of large-diameter metal-on-metal prostheses, particularly in the elderly, we performed cementless total hip arthroplasty (THA) using metal-on-metal prostheses with large-diameter femoral heads (mean, 45 mm) in 59 patients (average age, 75.1 years) between January 2004 and December 2005. All procedures were performed using a posterolateral approach and spinal anesthesia. Average follow-up was 65 months. Pre- and postoperative Harris Hip Scores and SF-36 questionnaire results were recorded for all patients to evaluate the level of pain relief, improvement in physical function, and changes in quality of life. Postoperative radiographic images were used to document areas of osteolysis and probable aseptic loosening. Average preoperative Harris Hip Score was 36.1±5.7, compared to 69.4±8.3 at last follow-up (P<.01). Average preoperative SF-36 score was 33.6±7.4, compared to 71.8±6.4 at last follow-up (P<.01). There were no dislocations, aseptic loosening, or revisions. Our findings suggest that metal-on-metal cementless prostheses with large-diameter femoral heads in THA can produce satisfactory results with good durability, a low rate of dislocation and aseptic loosening, and a low incidence of revisions in the short term. The benefits of this technique for elderly patients, especially those with weak muscle power and reduced cognitive function, include avoidance of severe cement-injection complications and early functional recovery.