Crystalline Biomimetic Calcium Phosphate Coating on Mini-Pin Implants to Accelerate Osseointegration and Extend Drug Release Duration for an Orthodontic Application.

Miniscrew implants (MSIs) have been widely used as temporary anchorage devices in orthodontic clinics. However, one of their major limitations is the relatively high failure rate. We hypothesize that a biomimetic calcium phosphate (BioCaP) coating layer on mini-pin implants might be able to accelerate the osseointegration, and can be a carrier for biological agents. A novel mini-pin implant to mimic the MSIs was used. BioCaP (amorphous or crystalline) coatings with or without the presence of bovine serum albumin (BSA) were applied on such implants and inserted in the metaphyseal tibia in rats. The percentage of bone to implant contact (BIC) in histomorphometric analysis was used to evaluate the osteoconductivity of such implants from six different groups (n=6 rats per group): (1) no coating no BSA group, (2) no coating BSA adsorption group, (3) amorphous BioCaP coating group, (4) amorphous BioCaP coating-incorporated BSA group, (5) crystalline BioCaP coating group, and (6) crystalline BioCaP coating-incorporated BSA group. Samples were retrieved 3 days, 1 week, 2 weeks, and 4 weeks post-surgery. The results showed that the crystalline BioCaP coating served as a drug carrier with a sustained release profile. Furthermore, the significant increase in BIC occurred at week 1 in the crystalline coating group, but at week 2 or week 4 in other groups. These findings indicate that the crystalline BioCaP coating can be a promising surface modification to facilitate early osseointegration and increase the success rate of miniscrew implants in orthodontic clinics

Osteogenic Enhancement Between Icariin and Bone Morphogenetic Protein 2: A Potential Osteogenic Compound for Bone Tissue Engineering

Icariin, a typical flavonol glycoside, is the main active component of Herba Epimedii, which was used to cure bone-related diseases in China for centuries. It has been reported that Icariin can be delivered locally by biomaterials and it has an osteogenic potential for bone tissue engineering. Biomimetic calcium phosphate (BioCaP) bone substitute is a novel drug delivery carrier system. Our study aimed to evaluate the osteogenic potential when Icariin was internally incorporated into the BioCaP granules. The BioCaP combined with Icariin and bone morphogenetic protein 2 (BMP-2) was investigated in vitro using an MC3T3-E1 cell line. We also investigated its efficacy to repair 8 mm diameter critical size bone defects in the skull of SD male rats. BioCaP was fabricated according to a well-established biomimetic mineralization process. In vitro, the effects of BioCaP alone or BioCaP with Icariin and/or BMP-2 on cell proliferation and osteogenic differentiation of MC3T3-E1 cells were systematically evaluated. In vivo, BioCaP alone or BioCaP with Icariin and/or BMP-2 were used to study the bone formation in a critical-sized bone defect created in a rat skull. Samples were retrieved for Micro-CT and histological analysis 12 weeks after surgery. The results indicated that BioCaP with or without the incorporation of Icariin had a positive effect on the osteogenic differentiation of MC3T3-E1. BioCaP with Icariin had better osteogenic efficiency, but had no influence on cell proliferation. BioCap + Icariin + BMP-2 showed better osteogenic potential compared with BioCaP with BMP-2 alone. The protein and mRNA expression of alkaline phosphatase and osteocalcin and mineralization were higher as well. In vivo, BioCaP incorporate internally with both Icariin and BMP-2 induced significantly more newly formed bone than the control group and BioCaP with either Icariin or BMP-2 did. Micro-CT analysis revealed that no significant differences were found between the bone mineral density induced by BioCaP with icariin and that induced by BioCaP with BMP-2. Therefore, co-administration of Icariin and BMP-2 was helpful for bone tissue engineering

Construction and verification of a risk model for re-positive peptic ulcer patients with <i>Helicobacter pylori</i> infection after eradication therapy

Objective To explore the risk factors of re-positive after eradication therapy in patients with peptic ulcer（PU） complicated with Helicobacter pylori（Hp）infection， and to establish and verify a risk warning. Methods A total of 120 patients with PU complicated with Hp infection who underwent eradication therapy were selected. According to whether the patients were re-positive， they were divided into the re-positive group（n = 17）and non-re-positive group（n = 103）. Logistic regression analysis was performed on potential related factors， and a risk model was constructed and verified. Results The re-positive rate of 120 PU patients complicated with Hp infection after eradication therapy was 14.17%. Logistic regression analysis showed that smoking history（OR = 3.255）， alcohol abuse history（OR = 5.170）， NSAID application history（OR = 3.136 ， gastroscopy after eradication therapy（OR = 6.545）， SAS score（OR = 1.119）， SDS score（OR = 1.210）， maximum diameter of ulcer（OR = 4.450）and number of ulcer（OR =1.307）were the independent risk factors for re-positive after eradication therapy in patients with PU complicated with Hp infection（all P &lt; 0.05）. Regular eating habit （OR = 0.034 ） was the independent protective factor（P &lt; 0.05）. The area under the ROC curve （AUC） was 0.949（P &lt; 0.001，95%CI 0.899-0.998）， the sensitivity was 88.20%， the specificity was 92.20%， and the maximum Youden index was 0.804. The prediction accuracy in clinical application was 81.67%. Conclusions The re-positive of PU patients complicated with Hp infection after eradication therapy is affected by multiple factors. The risk warning model established based on these risk factors yields high predictive efficacy

Biomimetic calcium phosphate coating on medical grade stainless steel improves surface properties and serves as a drug carrier for orthodontic applications

Objective: Recently, stainless steel (SSL) miniscrew implants have been used in orthodontic clinics as temporary anchorage devices. Although they have excellent physical properties, their biocompatibility is relatively poor. Previously, our group developed a two-phase biomimetic calcium phosphate (BioCaP) coating that can significantly improve the biocompatibility of medical devices. This study aimed to improve the biocompatibility of SSL by coating SSL surface with the BioCaP coating. Methods: Titanium (Ti) discs and SSL discs (diameter: 5 mm, thickness: 1 mm) were used in this study. To form an amorphous layer, the Ti discs were immersed in a biomimetic modified Tyrode solution (BMT) for 24 h. The SSL discs were immersed in the same solution for 0 h, 12 h, 24 h, 36 h and 48 h. To form a crystalline layer, the discs were then immersed in a supersaturated calcium phosphate solution (CPS) for 48 h. The surface properties of the BioCaP coatings were analysed. In addition, bovine serum albumin (BSA) was incorporated into the crystalline layer during biomimetic mineralisation as a model protein. Results: The morphology, chemical composition and drug loading capacity of the BioCaP coating on smooth SSL were confirmed. This coating improved roughness and wettability of SSL surface. In vitro, with the extension of BMT coating period, the cell seeding efficiency, cell spreading area and cell proliferation on the BioCaP coating were increased. Significance: These in vitro results show that the BioCaP coating can improve surface properties of smooth medical grade SSL and serve as a carrier system for bioactive agents

Gaining Soft Tissue with a Hydrogel Soft Tissue Expander: A Case Report

In this case report, we describe the treatment of a patient referred to our clinic with a hopeless tooth 21 with an attached pontic. The aim of this case report was to, first, describe the advantages and disadvantages of gaining soft tissue with a self-inflating soft tissue expander before performing a bone augmentation procedure in implant dentistry in the esthetic zone. Second, we describe how an amalgam tattoo, caused by a previously performed apicoectomy that made the extension of the raised flap to cover the augmented site esthetically undesirable, was removed. Two silicone enveloped Osmed hydrogel self-inflating soft tissue expanders were placed submucosally on the right- and left-hand side of the amalgam tattoo. One of these two perforated the overlaying mucosa after 24 days. Both tissue expanders were removed, the amalgam tattoo was excided, the site augmented, and an implant with a crown and a pontic was placed

The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds

We investigated the inflammatory response to, and the osteoinductive efficacies of, four polymers (collagen, Ethisorb, PLGA and Polyactive) that bore either an adsorbed (fast-release kinetics) or a calcium-phosphate-coating-incorporated (slow-release kinetics) depot of BMP-2. Titanium-plate-supported discs of each polymer (n = 6 per group) were implanted at an ectopic (subcutaneous) ossification site in rats (n = 48). Five weeks later, they were retrieved for a histomorphometric analysis of the volumes of ectopic bone and foreign-body giant cells (a gauge of inflammatory reactivity), and the degree of polymer degradation. For each polymer, the osteoinductive efficacy of BMP-2 was higher when it was incorporated into a coating than when it was directly adsorbed onto the material. This mode of BMP-2 carriage was consistently associated with an attenuation of the inflammatory response. For coated materials, the volume density of foreign-body giant cells was inversely correlated with the volume density of bone (r(2) = 0.96), and the volume density of bone was directly proportional to the surface-area density of the polymer (r(2) = 0.97). Following coating degradation, other competitive factors, such as the biocompatibility and the biodegradability of the polymer itself, came into play

Biomimetic coating of organic polymers with a protein-functionalized layer of calcium phosphate: the surface properties of the carrier influence neither the coating characteristics nor the incorporation mechanism or release kinetics of the protein

Polymers that are used in clinical practice as bone-defect-filling materials possess many essential qualities, such as moldability, mechanical strength and biodegradability, but they are neither osteoconductive nor osteoinductive. Osteoconductivity can be conferred by coating the material with a layer of calcium phosphate, which can be rendered osteoinductive by functionalizing it with an osteogenic agent. We wished to ascertain whether the morphological and physicochemical characteristics of unfunctionalized and bovine-serum-albumin (BSA)-functionalized calcium-phosphate coatings were influenced by the surface properties of polymeric carriers. The release kinetics of the protein were also investigated. Two sponge-like materials (Helistat® and Polyactive®) and two fibrous ones (Ethisorb and poly[lactic-co-glycolic acid]) were tested. The coating characteristics were evaluated using state-of-the-art methodologies. The release kinetics of BSA were monitored spectrophotometrically. The characteristics of the amorphous and the crystalline phases of the coatings were not influenced by either the surface chemistry or the surface geometry of the underlying polymer. The mechanism whereby BSA was incorporated into the crystalline layer and the rate of release of the truly incorporated depot were likewise unaffected by the nature of the polymeric carrier. Our biomimetic coating technique could be applied to either spongy or fibrous bone-defect-filling organic polymers, with a view to rendering them osteoconductive and osteoinductive

Enhanced biocompatibility and improved osteogenesis of coralline hydroxyapatite modified by bone morphogenetic protein 2 incorporated into a biomimetic coating.

OBJECTIVES (1) To determine whether the biocompatibility of coralline hydroxyapatite (CHA) granules could be improved by using an octacalcium phosphate (OCP) coating layer, and/or functionalized with bone morphogenetic protein 2 (BMP-2), and (2) to investigate if BMP-2 incorporated into this coating is able to enhance its osteoinductive efficiency, in comparison to its surface-adsorbed delivery mode. METHODS CHA granules (0.25 g per sample) bearing a coating-incorporated depot of BMP-2 (20 μg/sample) together with the controls (CHA bearing an adsorbed depot of BMP-2; CHA granules with an OCP coating without BMP-2; pure CHA granules) were implanted subcutaneously in rats (n = 6 animals per group). Five weeks later, the implants were retrieved for histomorphometric analysis to quantify the volume of newly generated bone, bone marrow, fibrous tissue and foreign body giant cells (FBGCs). The osteoinductive efficiency of BMP-2 and the rates of CHA degradation were also determined. RESULTS The group with an OCP coating-incorporated depot of BMP-2 showed the highest volume and quality or bone, and the highest osteoinductive efficacy. OCP coating was able to reduce inflammatory responses (improve biocompatibility), and also simple adsorption of BMP-2 to CHA achieved this. CONCLUSIONS The biocompatibility of CHA granules (reduction of inflammation) was significantly improved by coating with a layer of OCP. Pure surface adsorption of BMP-2 to CHA also reduced inflammation. Incorporation of BMP-2 into the OCP coatings was associated with the highest volume and quality of bone, and the highest biocompatibility degree of the CHA granules. CLINICAL SIGNIFICANCE Higher osteoinductivity and improved biocompatibility of CHA can be obtained when a layer of BMP-2 functionalized OCP is deposited on the surfaces of CHA granules

Anti-fouling membranes by manipulating surface wettability and their anti-fouling mechanism

This study aims to compare the anti-wetting and anti-fouling surface behavior in membrane distillation (MD) by two surface modification routes on porous polyvinylidene fluoride (PVDF) membranes. A superhydrophobic membrane (SiO2-PFTS/PVDF) was obtained by dynamically forming 1H,1H,2H,2H-perfluorooctyl trichlorosilane containing SiO2 nanoparticles on the membrane surface as in our previous study; whereas a superhydrophilic membrane (PVA/PVDF) was developed by attaching a thin layer of poly(vinylalcohol) hydrogel onto the membrane's surface. The effects of surface modification on their anti-wetting or anti-fouling properties were examined in MD using an aqueous NaCl solution with various organic foulants (e.g., kerosene, humic acid (HA), and sodium dodecyl benzene sulfonate (SDBS)). The results showed that the superhydrophobic SiO2-PFTS/PVDF membrane displayed excellent self-cleaning characteristics and wetting resistance against all three studied foulants. In contrast, the hydrophilic surface layer of the PVA/PVDF membrane only slowed down wetting and fouling when in contact with kerosene and HA. Nonetheless, when dealing with SDBS, its anti-wettability performance was comparable to that of the SiO2-PFTS/PVDF membrane. The superhydrophobic SiO2-PFTS/PVDF membrane exhibited anti-fouling and anti-wetting behaviors even though the extended Derjaguin–Landau–Verwey–Overbeek theory indicated the attraction force between the membrane surface and all three foulants

Curcumin in Osteosarcoma Therapy: Combining With Immunotherapy, Chemotherapeutics, Bone Tissue Engineering Materials and Potential Synergism With Photodynamic Therapy

Osteosarcoma is a dominating malignant bone tumor with high mortality due to pulmonary metastases. Furthermore, because of the cancer cell erosion and surgery resection, osteosarcoma always causes bone defects, which means dysfunction and disfigurement are seldom inevitable. Although various advanced treatments (e.g. chemotherapy, immunotherapy, radiotherapy) are coming up, the 5-year survival rate for osteosarcoma with metastases is still dismal. In line with this, the more potent treatments for osteosarcoma are in high demand. Curcumin, a perennial herb, has been reportedly applied in the therapy of various types of tumors via different mechanisms. In vitro, it has also been reported that curcumin can inhibit the proliferation of osteosarcoma cell lines and can be used to repair bone defects. This seems curcumin is a promising candidate in osteosarcoma treatment. However, due to its congenital property like hydrophobicity, and low bioavailability, affecting its anticancer effect, clinical applications of curcumin are highly limited. To enhance its performance in cancer therapies, some synergist approaches with curcumin have emerged. The present review presents some prospective ones (i.e. combinations with immunotherapy, chemotherapeutics, bone tissue engineering, and biomaterials) applied in osteosarcoma treatment. Additionally, with the advancements of photodynamic therapy in cancer therapy, this review also prospects the combination of curcumin with photodynamic therapy in osteosarcoma treatment