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Due to its adverse health and environmental impacts, groundwater contamination by toxic organic compounds such as chlorinated solvents is a global concern. The slow-release permanganate gel (SRP-G) is a mixture of potassium permanganate (KMnO4) and colloidal silica solution. The SRP-G is designed to radially spread after injection via wells, gelate in situ to form gel barriers containing permanganate (MnO4-), and slowly release MnO4- to treat plumes of chlorinated solvents in groundwater. This study aimed to characterize the effects of temperature on the dynamics of SRP-G in saturated porous media. In gelation batch tests, the viscosity of ambient-temperature (24 °C) SRP-G with 30 g/L-KMnO4 was 21 cP at 70 min, 134 cP at 176 min, and peaked at 946 cP to solidification at 229 min. The viscosity of low-temperature (4 °C) SRP-G with 30 g/L-KMnO4 was 71 cP at 273 min, 402 cP at 392 min, and peaked at 818 cP to solidification at 485 min. A similar pattern, e.g., increased gelation lag time with low-temperature SRP-G, was observed for SRP-Gs with 40 g/L, 50 g/L, and 60 g/L KMnO4. In flow-through tests using a glass column filled with saturated sands, injection rates, spreading rates, and release durations were 0.6 mL/min, 46 mm/min, and 33 h for KMnO4(aq), 0.2 mL/min, 2 mm/min, and 38 h for ambient-temperature SRP-G, and 0.4 mL/min, 16 mm/min, and 115 h for low-temperature SRP-G, respectively. These results indicated that the injectability, injection rate, and gelation lag time of SRP-G and the size, release rate, and release duration of MnO4- gel barriers can be increased at low temperatures. The low-temperature SRP-G scheme can be useful for treating large or dilute dissolved plumes of chlorinated solvents or other pollutants in groundwater.

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Research in intelligent drug delivery systems within the field of biomedicine promises to enhance drug efficacy at disease sites and reduce associated side effects. Mesoporous silica nanoparticles (MSNs), characterized by their large specific surface area, appropriate pore size, and excellent biocompatibility, have garnered significant attention as one of the most effective carriers for drug delivery. The hydroxyl groups on their surface are active functional groups, facilitating easy functionalization. The installation of controllable molecular machines on the surface of mesoporous silica to construct nanovalves represents a crucial advancement in developing intelligent drug delivery systems (DDSs) and addressing the issue of premature drug release. In this review, we compile several notable and illustrative examples of MSNs and discuss their varied applications in DDSs. These applications span regulated and progressive drug release mechanisms. MSNs hold the potential to enhance drug solubility, improve drug stability, and mitigate drug toxicity, attributable to their ease of functionalization. Furthermore, intelligent hybrid nanomaterials are being developed, featuring programmable properties that react to a broad spectrum of stimuli, including light, pH, enzymes, and redox triggers, through the use of molecular and supramolecular switches.

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Since hydroxyapatite (HAp) is an important constituent of bone and teeth, it has excellent biocompatibility and bioactivity, good osteoconductive effects and the ability to induce bone formation as a material for bone or tooth repair and replacement. At present, widely used HAp microspheres have some characteristics, such as large specific surface area, light mass, good injection properties, good fluidity, and low aggregation ability, but they are difficult to really meet the biological and clinical needs due to their own mechanical property defects, such as low strength, brittleness, and poor plasticity. Based on the current research status of HAp microspheres, we summarize the research progress of various types of composite microspheres, including inorganic materials, natural polymer materials and synthetic polymer materials, and further analyze the advantages of HAp composite microspheres loaded with drug molecules, proteins and bioactive factors, so as to explore the development prospect of HAp composite microspheres as scaffolds for constructing sustained release systems. It provides a theoretical basis and research direction to prepare HAp composite micro-spheres with superior comprehensive properties so that they can be better applied in bone tissue regeneration and tooth regeneration engineering.

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BACKGROUND:Previous research by the research team found that domestically produced porous tantalum is beneficial for early adhesion and proliferation of MG63 cells,and can be used as a scaffold material for bone tissue engineering. OBJECTIVE:To investigate the effect of domestic porous tantalum modified by osteogenic induction factor slow-release system on the adhesion,proliferation,and differentiation of MG63 cells. METHODS:Osteogenic induction factor slow-release system was constructed by adding 15%volume fraction of osteogenic factor solution to poly(lactic-co-glycolic-acid)gel.The passage 3 MG63 cells were inoculated on a porous tantalum surface(control group),porous tantalum surface coated with poly(lactic-co-glycolic-acid)copolymer gel(gel group),and porous tantalum surface coated with osteoblastic induction factor slow-release system(slow-release system group),and co-cultured for 5 days.The surface cytoskeleton of the material was observed by phalloidine staining.Cell proliferation was detected by flow cytometry.Western blot assay and RT-qPCR were used to detect the protein and mRNA expressions of type Ⅰ collagen,osteopontin,and RUNX-2 on the surface cells of the material. RESULTS AND CONCLUSION:(1)Phalloidine staining showed that MG63 cells adhered to and grew on the surface and inside of the three groups of porous tantalum,and the matrix secreted by the cells covered the surface of the material.(2)Flow cytometry showed that the cell proliferation in the slow-release system group was faster than that in the control group and the gel group(P<0.05).(3)Western blot assay and RT-qPCR showed that the protein and mRNA expressions of type Ⅰ collagen,osteopontin,and RUNX-2 in the slow-release system group were higher than those in the control group and gel group(P<0.05).(4)The results showed that the domestic porous tantalum modified by the osteogenic induction factor slow-release system was beneficial to the adhesion,proliferation,and differentiation of MG63 osteoblasts.

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In recent years, bone tissue engineering (BTE) has played an essential role in the repair of bone tissue defects. Although bioactive factors as one component of BTE have great potential to effectively promote cell differentiation and bone regeneration, they are usually not used alone due to their short effective half-lives, high concentrations, etc. The release rate of bioactive factors could be controlled by loading them into scaffolds, and the scaffold microstructure has been shown to significantly influence release rates of bioactive factors. Therefore, this review attempted to investigate how the scaffold microstructure affected the release rate of bioactive factors, in which the variables included pore size, pore shape and porosity. The loading nature and the releasing mechanism of bioactive factors were also summarized. The main conclusions were achieved as follows: i) The pore shapes in the scaffold may have had no apparent effect on the release of bioactive factors but significantly affected mechanical properties of the scaffolds; ii) The pore size of about 400 µm in the scaffold may be more conducive to controlling the release of bioactive factors to promote bone formation; iii) The porosity of scaffolds may be positively correlated with the release rate, and the porosity of 70%-80% may be better to control the release rate. This review indicates that a slow-release system with proper scaffold microstructure control could be a tremendous inspiration for developing new treatment strategies for bone disease. It is anticipated to eventually be developed into clinical applications to tackle treatment-related issues effectively.

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Fracturing technology that can enhance the delivery of amendments has attracted attention in the remediation of low-permeability contaminated sites. However, there are few works on the enhanced delivery of amendments based on multi-point injection in a fracture-matrix system. This study develops a two-dimensional analytical model for enhanced delivery of amendments in a finite-domain low-permeability matrix through multi-point injection in a natural, hydraulic or pneumatic fracture. The mechanisms of advection, diffusion, dispersion, sorption and degradation are considered in the model and any injection form (e.g., pulse injection, periodic injection or slow-release injection) can be embedded to obtain a specified solution. Then, a new linear factor R*, which is the ratio of the peak concentration to the trough concentration on the same plane, is introduced to evaluate the concentration fluctuation in the fracture and matrix. Results show that with a stronger line source formed in the fracture right after injection (corresponding to a small R*), the concentration distribution of amendments in the matrix is more uniform at each depth resulting in a smaller residual rate, i.e., (R*-1) × 100%. If the injection wells have been installed unreasonably (e.g., a too large spacing), the continuous injection time is an effective controllable parameter to compensate for this defect. Moreover, a controlled slow-release system can maintain a more stable concentration distribution in the fracture than continuous injection and periodic injection systems, giving a longer residence time. Overall, this work is expected to provide some interesting guidelines for the design of multi-point injection in the fracturing low-permeability sites to enhance the remediation of contaminated soil.

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In contrast to the early acting bone morphogenetic protein 2, bone morphogenetic protein 7 (BMP7) plays a decisive role mainly in the late stages of bone formation. To overcome deactivation and degradation of expensive BMP7, we designed a novel long-acting BMP7 release system based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) nanoparticles to enable the induction of osteogenic differentiation in human adipose mesenchymal stem cells (ADSCs). In order to improve the encapsulation efficiency of BMP7 and avoid damage by organic solvents, BMP7 was modified and protected using the biosurfactant soybean lecithin. In an in vitro test, BMP7-soybean lecithin-P34HB nanoparticles (BMP7-SPNPs) showed a short initial burst of BMP7 release during the first 24h, followed by a steady increase to a cumulative 80% release in 20days. Compared with the rapid release of control P34HB nanoparticles without soybean phospholipids loaded with BMP7 without soybean lecithin, BMP7-SPNPs significantly reduced the initial burst of BMP7 release and stabilized the content of BMP7 to allow long-term osteogenic differentiation during the late phase of bone development. Human ADSCs treated with BMP7-SPNPs showed higher alkaline phosphatase activity and higher expression levels of genetic markers of osteogenic differentiation compared with the control group. Thus, the results indicate that BMP7-SPNPs can be used as a rapid and long-acting BMP7 delivery system for osteogenic differentiation.

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BACKGROUND: Retinoblastoma (Rb) is one of the most common malignancies among children. Following early diagnosis and prompt treatment, the clinical outcome or prognosis of Rb is promising. However, the prognosis or survival rates of patients with late-stage Rb remain poor. Current therapeutic strategies for advanced Rb mainly involve the use of advanced chemotherapeutic options. However, the efficacy of these strategies is not satisfactory. Therefore, the development of novel strategies to achieve a more effective antitumor effect on late-stage Rb is of crucial importance. METHODS AND MATERIALS: Topotecan was dissolved in phosphate-buffered saline and prepared into a temperature-sensitive phase-change hydrogel (termed Topo-Gel). Moreover, Topo-Gel was injected into tumor tissues formed by Y79 cells (an Rb cell line) in nude mice to examine the long-term release and long-acting antitumor effect of Topo-Gel on Rb tumors. RESULTS: Topo-Gel transforms from liquid to a hydrogel at near body temperatures (phase-change temperature [T1/2] was 37.23±0.473 °C), and maintains the slow release of topotecan in Rb tumor tissues. Following the subcutaneous injection of Topo-Gel, the treatment induced long-acting inhibition of tumor growth and relieved the adverse effects associated with topotecan. Topo-Gel, a temperature-sensitive phase-change hydrogel, is a slow-release system that prolongs the presence of topotecan in Rb tissues, and preserves the efficacy of topotecan in the long term. CONCLUSION: Preparation of topotecan into a temperature-sensitive phase-change hydrogel achieves a long-term sustained antitumor effect on Rb cells, and may be a useful strategy for the treatment of intraocular Rb.

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The use of biomaterials and signaling molecules to induce bone formation is a promising approach in the field of bone tissue engineering. Follistatin (FST) is a glycoprotein able to bind irreversibly to activin A, a protein that has been reported to inhibit bone formation. We investigated the effect of FST in critical processes for bone repair, such as cell recruitment, osteogenesis and vascularization, and ultimately its use for bone tissue engineering. In vitro, FST promoted mesenchymal stem cell (MSC) and endothelial cell (EC) migration as well as essential steps in the formation and expansion of the vasculature such as EC tube-formation and sprouting. FST did not enhance osteogenic differentiation of MSCs, but increased committed osteoblast mineralization. In vivo, FST was loaded in an in situ gelling formulation made by alginate and recombinant collagen-based peptide microspheres and implanted in a rat calvarial defect model. Two FST variants (FST288 and FST315) with major differences in their affinity to cell-surface proteoglycans, which may influence their effect upon in vivo bone repair, were tested. In vitro, most of the loaded FST315 was released over 4 weeks, contrary to FST288, which was mostly retained in the biomaterial. However, none of the FST variants improved in vivo bone healing compared to control. These results demonstrate that FST enhances crucial processes needed for bone repair. Further studies need to investigate the optimal FST carrier for bone regeneration.

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BACKGROUND: The high ureolytic activity of rumen microbiota is a concern when urea is used in ruminant feed, because it leads to fast urea conversion, resulting in possible intoxication and lower nitrogen utilization. This study intended to microencapsulate urea using carnauba wax to obtain slow-release systems in the rumen. The experiment was conducted in a randomized block design, arranged in a 3 × 2 factorial, with the urea encapsulated with carnauba wax in ratios of 1 : 2; 1 : 3, and 1 : 4 (UME 2; UME 3, and UME 4) and two particles sizes (small, PS ; and large, PL ). RESULTS: All formulations showed excellent properties, including inhibition of urea hygroscopicity. The formulation UME 2 exhibited the greatest yield (91.6%) and microencapsulation efficiency (99.6%) values, whereas the formulation UME 4 presented the greatest thermal stability (259.5 °C) and lowest moisture content (1.81%). The UME 2 formulation presented a slower release than the other UME formulations studied. CONCLUSION: The production of urea microspheres using carnauba wax was successful for all microencapsulated systems developed, evidencing the promising potential for use in ruminant animal diets. The UME 2 formulation with large particles is the most recommended because it permitted greater resistance to microbial attack, allowing a slower release of urea into the rumen, reducing the risk of intoxication or ruminal alkalosis. © 2018 Society of Chemical Industry.

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New solutions for large bone defect repair are needed. Here, in situ gelling slow release systems for bone induction are assessed. Collagen-I based Recombinant Peptide (RCP) microspheres (MSs) are produced and used as a carrier for bone morphogenetic protein 2 (BMP-2). The RCP-MSs are dispersed in three hydrogels: high mannuronate (SLM) alginate, high guluronate (SLG) alginate, and thermoresponsive hyaluronan derivative (HApN). HApN+RCP-MS forms a gel structure at 32 ºC or above, while SLM+RCP-MS and SLG+RCP-MS respond to shear stress displaying thixotropic behavior. Alginate formulations show sustained release of BMP-2, while there is minimal release from HApN. These formulations are injected subcutaneously in rats. SLM+RCP-MS and SLG+RCP-MS loaded with BMP-2 induce ectopic bone formation as revealed by X-ray tomography and histology, whereas HApN+RCP-MS do not. Vascularization occurs within all the formulations studied and is significantly higher in SLG+MS and HApN+RCP-MS than in SLM+RCP-MS. Inflammation (based on macrophage subset staining) decreases over time in both alginate groups, but increases in the HApN+RCP-MS condition. It is shown that a balance between inflammatory cell infiltration, BMP-2 release, and vascularization, achieved in the SLG+RCP-MS alginate condition, is optimal for the induction of de novo bone formation.

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Cartilage tissue is characterized by its poor regenerative properties, and the clinical performance of cartilage grafts to replace cartilage defects has been unsatisfactory. Recently, cartilage regeneration with mature chondrocytes and stem cells has been developed and applied in clinical settings. However, there are challenges with the use of mature chondrocytes and stem cells for tissue regeneration, including the high costs associated with the standard stem cell isolation methods and the decreased cell viability due to cell manipulation. Previous studies demonstrated that cartilage can be regenerated from chondrocyte clusters that contain stem cells. Based upon some of the existing techniques, the goal of this study was to develop a novel and practical method to induce cartilage regeneration. A microslicer device was developed to process cartilage tissues into micron-size cartilage (microcartilage) in a minimally invasive manner. We evaluated microcartilage sizes and demonstrated 100-400 µm as optimal for generating a high cell yield with collagenase digestion. In addition, autologous intrafascial implantation of the composites of microcartilage and an absorbable scaffold with a slow-release system of basic fibroblast growth factor (bFGF) was carried out to induce cartilage regeneration. Our results demonstrated that the extent of bFGF diffusion depends on the size of microcartilage, and that cartilage regeneration was induced most effectively with 100 µm of microcartilage via SOX5 upregulation. These findings suggest that cartilage regeneration is possible with microcartilage as a source of cells without ex vivo cell expansion.

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Objective Studies have shown that low concentrations of nicotine can promote neovascularization and promote wound healing.This article aimed to investigate the influence of low concentration collagen membrane slow-release system on the hard palate trauma of rats.Methods Using poly(lactic acid-co-glycolic acid) (PLGA) copolymer as carrier materials, low concentration nicotine sustained-release particles were prepared by emulsion evaporation method (w/o/w), using collagen membrane as the brace and establish a low concentration collagen membrane system.48 Wistar rats were divided into experimental group and blank group, 3 mm diameter circular wound was made in the forepart palate.Low concentration of nicotine collagen membrane sustained-release particle system and blank collagen membrane (control) were sutured on the wound with 6-0 absorbable thread.Then, observed the wound healing of 0, 3, 7, 10 days and compared the healing differences between each groups.Results Under the electron microscope, the nicotine sustained-release particles were circular, similar size with rough surface, the average diameter were 3.0±0.2μm, the encapsulation efficiency and drug loading rate was 50.2% and 4.12% respectively.In vitro, nicotine sustained-release particles released much more nicotine on the first day, less on the second day, tends to stable and fluctuate within a certain range from the third day on, and declined sharply after about 10 days, nicotine concentration from 3rd to 10th day was fluctuate within 10-5-10-4mol/L.Postoperative wound healing, no significant difference in 3 days(P>0.05), after 7 days, the wound healing of experimental group significantly greater compared with the control (P=0.015).The wound was healed in 10 days after operative, there was no significant difference between two groups(P>0.05).The epithelial proliferation in the experimental group was significantly greater than that in the blank group, there were many fibroblasts, inflammatory cells and new capillaries, the epithelial process is short, the submucosa is loose, and a large number of collagen fibers are produced.The lamina propria is closely connected with the periosteum, and the wound is healed Conclusion Low concentration of nicotine sustained-release particles collagen membrane system may promote wound healing in the hard palate mucosa of rats.

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Slow-release permanganate (MnO4(-)) gel (SRP-G) is a hyper-saline KMnO4 solution that can be used for treating large, dilute, or deep plumes of chlorinated solvents in groundwater. Ideally, the SRP-G injected into aquifers will slowly gelate to form MnO4(-) gel in situ, and the gel will slowly releases MnO4(-). Objectives of this study were to develop SRP-G using colloidal silica as gelling solution, characterize its gelation and release kinetics, and delineate its dynamics in a saturated sandy media. The SRP-G exhibited a two-phase increase in viscosity: a lag phase characterized by little increase in viscosity followed by a short gelation phase. Gelation lag times of SRP-G solutions increased (from 0.5h to 13d) with decreasing KMnO4 concentrations (from 25 to 8 g L(-1)). Permanganate release from gelated SRP-G increased with increasing KMnO4 concentrations, and was characterized as asymptotic release with initial peak (0.9-2.2 mg min(-1)) followed by more attenuated release. Gelation lag times of SRP-G flowing in sands (linear velocity=2.1md(-1)) increased (1, 3, and 6h) with decreasing KMnO4 concentrations (25.0, 23.0, and 22.9 g L(-1)). Permanganate release from gelated SRP-Gs continued for up to 3d and was characterized as asymptotic release with an initial peak release (∼1.2 g min(-1)) followed by more attenuated release over 70h. Dilution of SRP-G by dispersion in porous media affects gelation and release kinetics. Increasing the silica concentration in the SRP-G may facilitate gelation and extend the duration of MnO4(-) release from emplaced SRP-G in porous media.

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