Bone cement distribution may significantly affect the efficacy of percutaneous vertebroplasty in treating symptomatic Schmorl's nodes.

PURPOSE: Percutaneous vertebroplasty(PVP) has been widely used in treating symptomatic Schmorl's nodes(SNs). However, there were still some patients with poor pain relief. At present, there is a lack of research to analyze the reasons for poor efficacy. METHODS: Review the SNs patients treated with PVP in our hospital from November 2019 to June 2022, collect their baseline data. Reverse reconstruction software was used to calculate the filling rate of bone edema ring(Rf). NRS score was used to evaluate pain and ODI to evaluate function. The patients were divided into remission group(RG) and non remission group(n-RG) according to symptom. In addition, according to the Rf, they were divided into excellent, good and poor groups. Differences between groups were investigated. RESULTS: A total of 26 vertebrae were included in 24 patients. When grouped according to symptoms, patients in n-RG were older, and surgical segments were tend to locate in lower lumbar spine. The proportion of Poor distribution was significantly higher. When grouped according to the cement distribution, the preoperative NRS and ODI of the three groups were comparable, but the NRS and ODI of Poor group were significantly worse than the Excellent and Good groups postoperatively and at the last follow-up. CONCLUSIONS: The cement distribution may significantly affect the efficacy of PVP in treating symptomatic SNs. We suggest that the bone edema ring should be filled as fully as possible to ensure the efficacy. In addition, advanced age and low lumbar lesions are also adverse factors for clinical outcomes.

The role of conformational dynamics in the activity of polymer-conjugated CalB in organic solvents.

Perennial interest in enzyme catalysis has been expanding its applicability from aqueous phases where enzymes are naturally evolved to organic solvents in which the majority of industrial chemical syntheses are carried out. Although conjugating an enzyme with a soluble polymer has been attempted to enhance enzyme activity in organic solvents, the underlying mechanism remains poorly understood in terms of the conformational dynamics and enzyme activity. Herein, we combine LF-NMR measurements and MD simulations to investigate the effects of polymer grafting on the conformational dynamics of CalB in organic solvents and the consequential impacts on the catalytic kinetics, using the lipase-catalyzed transesterification reaction as a model system. LF-NMR measurements confirm that conjugation with a soluble polymer improves the enzyme flexibility in organic solvents, leading to an increase in the catalytic efficiency of up to two orders of magnitude. MD simulations suggest that the conjugated enzyme samples a larger conformational space, compared to its native counterpart, validating the hypothesis that polymer motion enhances enzyme dynamics. These experimental and simulation results provide new insights for enhancing enzyme conformational dynamics and thereby catalytic kinetics in organic solvents.

Nanoparticles Penetrate into the Multicellular Spheroid-on-Chip: Effect of Surface Charge, Protein Corona, and Exterior Flow.

Nanoparticles (NPs) are widely studied as tumor targeted vehicles. The penetration of NPs into the tumor is considered as a major barrier for delivery of NPs into tumor cell and a big challenge to translate NPs from lab to the clinic. The objective of this study is to know how the surface charge of NPs, the protein corona surrounding the NPs, and the fluid flow around the tumor surface affect the penetration and accumulation of NPs into the tumor, through in vitro penetration study based on a spheroid-on-chip system. Surface decorated polystyrene (PS) NPs (100 nm) carrying positive and negative surface charge were loaded to the multicellular spheroids under static and flow conditions, in the presence or absence of serum proteins. NP penetration was investigated by confocal laser microscopy scanning followed with quantitative image analysis. The results reveal that negatively charged NPs are attached more on the spheroid surface and easier to penetrate into the spheroids. Protein corona, which is formed surrounding the NPs in the presence of serum protein, changes the surface properties of the NPs, weakens the NP-cell affinity, and, therefore, results in lower NP concentration on the spheroid surface but might facilitate deeper penetration. The exterior fluid flow enhances the interstitial flow into the spheroid, which benefits the penetration but also strips the NPs (especially the NPs with protein corona) on the spheroid surface, which decreases the penetration flux significantly. The maximal penetration was obtained by applying negatively charged NPs without protein corona under the flow condition. We hope the present study will help to understand the spatiotemporal performance of drug delivery NPs and inform the rational design of NPs with highly defined drug accumulation localized at a target site.

pH-Triggered Drug Release of Monodispersed P(St-co-DMAEMA) Nanoparticles: Effects of Swelling, Polymer Chain Flexibility and Drug-Polymer Interactions.

Monodispersed pH-sensitive poly(styrene-co-N,N'-dimethylaminoethyl methacrylate) (P(St-co- DMAEMA)) nanoparticles (NPs) were synthesized by emulsion polymerization for use in potential applications in targeted drug delivery to the tumor microenvironment. pH-Sensitive volume swelling and drug release of the NPs with varied St/DMAEMA molar ratios, crosslinking degrees and model drug coumarin-6 loading were explored in vitro to elucidate the pH-sensitive drug release mechanisms. The swelling of the NPs, which accounts for the electrostatic repulsion of protonated tertiary amine groups under acidic conditions, reaches maximum at low pH, low crosslinking density and high DMAEMA content. The NPs undergo a pH-triggered drug release, and under the condition of pH 5 and pH 2, the average release rate during 24 h is 1.5-fold and 3-fold higher than that at physiological pH, respectively. The pH-triggered drug release is related to pH-sensitive swelling, polymer chain flexibility and drug-polymer interaction, and is significantly impacted by the St/DMAEMA molar ratio, degree of crosslinking and drug loading.

Effect of oxygen-containing functional groups on the micromechanical behavior of biodegradable plastics and their formation of microplastics during aging.

Biodegradable plastics (BPs) are more prone to generate harmful microplastics (MPs) in a short time, which have always been ignored. Oxygenated functional group formation is considered to be a key indicator for assessing microplastic formation, while it is difficult to characterize at a very early stage. The micromechanical properties of the aging plastic during the formation of the MPs are highly influenced by the evolution of oxygen-containing functional groups, however, their relationship has rarely been revealed. Herein, we compared changes in the physicochemical properties of BPs and non-degradable plastic bags during aging in artificial seawater, soil, and air. The results showed that the oxidation of plastics in the air was the most significant, with the most prominent oxidation in BPs. The accumulation of carbonyl groups leads to a significant increase in the micromechanical properties and surface brittleness of the plastic, further exacerbating the formation of MPs. It was also verified by the FTIR, 2D-COS, AFM, and Raman spectroscopy analyses. Furthermore, the increased adhesion and roughness caused by oxygen-containing functional groups suggest that the environmental risks of BPs cannot be ignored. Our findings suggest that the testing of micromechanical properties can predicate the formation of the MPs at an early stage.

Preparation and evaluation of paclitaxel-loaded nanoparticle incorporated with galactose-carrying polymer for hepatocyte targeted delivery.

OBJECTIVE: Paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles incorporated with galactose-carrying polymer poly(vinyl benzyllactonamide) (PVLA) were prepared to facilitate the hepatocyte cell targeted delivery of paclitaxel via ligand-receptor mediated endocytosis. The factors impacting nanoparticle properties, drug release and cellular uptake efficiency were evaluated in vitro. METHOD: Paclitaxel-loaded nanoparticles incorporated with PVLA were prepared by emulsion solvent evaporation method with polyvinyl alcohol (PVA) as co-emulsifier. The presence of PVLA on the particle surface was investigated through the change of ζ potential and surface hydrophobicity. Cellular uptake and cytotoxic activity, involving factors concerned with them, were evaluated by HepG2 cells in vitro. RESULTS: The presence of PVLA led to the increase of ζ potential, reduction of the particle surface hydrophobicity, slight promotion of paclitaxel encapsulation efficiency and more homogeneous particle size, but excessive PVLA accelerated the burst release. With enhanced attachment and cellular uptake efficiency, the PVLA incorporated nanoparticles exhibited significant cytotoxicity to HepG2 cells, and particles with higher PVLA-to-PLGA ratio, although had larger size and almost the same cellular uptake efficiency, performed much higher cytotoxic activity due to the larger drug capacity and faster release rate.

Biomechanical comparison of vertebral augmentation and cement discoplasty for the treatment of symptomatic Schmorl's node: a finite element analysis.

Percutaneous vertebral augmentation (PVA) and percutaneous cement discoplasty (PCD) are two relatively new minimally invasive surgeries for symptomatic Schmorl's reported in recent decade. However, the clinical evidence for the effectiveness of these two surgeries is insufficient. The purpose of this study was to compare the biomechanical benefits and risks of the two surgeries in order to analyze their biomechanical differences and effectiveness. We reconstructed Five lumbar finite element models via computed tomography data, including control model, PVA-ideal model, PVA-nonideal model, PCD-ideal model, and PCD-nonideal model. The stress and strain of Schmorl's nodes, bone marrow edema zone (BMEZ), affected endplate, and the overall stability of segment were analyzed and compared. The validity of our models was confirmed. As a result, the PVA-ideal model can significantly reduce the stress of Schmorl's node and the strain of BMEZ, while this effect is inappreciable in PVA-nonideal model. The PCD-ideal model significantly reduced the strain of Schmorl's nodes and BMEZ, and significantly improve segmental stability, but also resulted in a significant increase in the stress of Schmorl's nodes, BMEZ and endplates. The PCD-nonideal model not only lacks blocking effect, but also sharply increases the strain of Schmorl's nodes and BMEZ. Thus, We recommend that both PVA and PCD surgeries in ideal distribution facilitated a more stable paranodular biomechanical microenvironment. However, due to the possibility of poor biomechanical outcomes caused by the non-ideal cement distribution, the non-ideal distribution of bone cement needs to be remedied in practice.

Bioactive poly (methyl methacrylate) bone cement for the treatment of osteoporotic vertebral compression fractures.

Rationale: Poly (methyl methacrylate) (PMMA) bone cement is one of the most commonly used biomaterials for augmenting/stabilizing osteoporosis-induced vertebral compression fractures (OVCFs), such as percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP). However, its clinical applications are limited by its poor performance in high compressive modulus and weak bonding to bone. To address these issues, a bioactive composite bone cement was developed for the treatment of osteoporotic vertebral compression fractures, in which mineralized collagen (MC) was incorporated into the PMMA bone cement (MC-PMMA). Methods: The in vitro properties of PMMA and MC-PMMA composite bone cement were determined, including setting time, compressive modulus, adherence, proliferation, and osteogenic differentiation of rat bone mesenchymal stem cells. The in vivo properties of both cements were evaluated in an animal study (36 osteoporotic New Zealand female rabbits divided equally between the two bone cement groups; PVP at L5) and a small-scale and short-term clinical study (12 patients in each of the two bone cement groups; follow-up: 2 years). Results: In terms of value for PMMA bone cement, the handling properties of MC-PMMA bone cement were not significantly different. However, both compressive strength and compressive modulus were found to be significantly lower. In the rabbit model study, at 8 and 12 weeks post-surgery, bone regeneration was more significant in MC-PMMA bone cement (cortical bone thickness, osteoblast area, new bone area, and bone ingrowth %; each significantly higher). In the clinical study, at a follow-up of 2 years, both the Visual Analogue Score and Oswestry Disability Index were significantly reduced when MC-PMMA cement was used. Conclusions: MC-PMMA bone cement demonstrated good adaptive mechanical properties and biocompatibility and may be a promising alternative to commercial PMMA bone cements for the treatment of osteoporotic vertebral fractures in clinical settings. While the present results for MC-PMMA bone cement are encouraging, further study of this cement is needed to explore its viability as an ideal alternative for use in PVP and BKP.

Monolithic osmotic tablet containing solid dispersion of 10-hydroxycamptothecin.

A novel monolithic osmotic tablet composed of solid dispersion of water-insoluble 10-hydroxycamptothecin (HCPT) was prepared. The tablet core was made of a suspending agent, polyethylene oxide, an osmotic agent, sodium chloride, and a solid dispersion consisting of polyethylene glycol 6000 and HCPT. Optimized formulation was able to deliver HCPT at the constant rate of 1.21 mg/hour for 12 hours with cumulative release above 90% in vitro, independent of environmental media and stirring rate, and the release rate is co-controlled by osmotic pressure, suspending effect, and drug solubility in solid dispersion. The monolithic osmotic tablet containing solid dispersion has great potential in the controlled delivery of water-insoluble drugs.

Mineralized Collagen Modified Polymethyl Methacrylate Bone Cement for Osteoporotic Compression Vertebral Fracture at 1-Year Follow-up.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: This study aimed to compare the clinical effects and imaging features of polymethyl methacrylate (PMMA) bone cement with and without mineralized collagen (MC) in percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). SUMMARY OF BACKGROUND DATA: PKP with PMMA is widely performed for OVCF. However, numerous complications have also been reported about the PMMA bone cement. Moreover, PMMA bone cement with and without MC have not been compared with respect to their postoperative efficacy and long-term follow-up. METHODS: From July 2016 to July 2017, 105 OVCF patients were randomly divided into two groups based on their PKP treatment: MC-PMMA group and PMMA group. Clinical operation, cement leakage, Oswestry Disability Index, visual analog scale, height of the fractured vertebrae, Cobb angle, refracture of the adjacent vertebra, recompression, and computed tomography values of the injured vertebra were compared between the two groups postoperatively and after 1-year follow-up. RESULTS: Clinical operation showed no differences between the two groups. Visual analog scale scores, Oswestry Disability Index scores, and Cobb angles showed statistically significant differences between the two groups after 1-year follow-up. The height of the vertebral body showed significant difference at 3 days postoperatively and preoperatively in each group and significant difference after 1 year between the two groups. The rate of refracture and leakage of the MC-PMMA group was lower than that of the PMMA group. The computed tomography value of the MC-PMMA group was obviously higher than that of the PMMA group after 1-year follow-up. CONCLUSION: MC-modified PMMA did not change the beneficial properties of PMMA. This new bone cement has better biocompatibility, can form a stable structure in the vertebral body, and improve the prognosis of patients by reducing pain and reoperation. LEVEL OF EVIDENCE: 3.

Synthesis of cholic-acid-carrying polymer and in-vitro evaluation of hepatoma-targeting nanoparticles decorated with the polymer.

The specific interaction between bile acids and the bile acids transporters provides a promising way for hepatoma-targeted drug delivery. We synthesized an amphipathic polymer containing cholic acid (CA), the main bile acids in body, and prepared CA-functionalized nanoparticles to target hepatoma cells. Poly-[3-(4-vinylbenzonate)-7, 12-dihydroxy-5-cholan-24-oic acid] (PVBCA) was synthesized by introducing methyl cholate onto polyvinyl benzoate polymer backbone, and was characterized by (1)H-NMR, FT-IR, and GFC. PVBCA can be incorporated onto PLGA nanoparticles surface via the emulsion-solvent evaporation procedure, resulting in the nanoparticles carrying CA moieties on their surface. The binding of CA moieties to the bile acids' transporters on the cell membrane enhances the cellular uptake of the nanoparticles significantly. The SMMC-7721 cell uptake of PVBCA-decorated nanoparticles increases with amount of incorporated PVBCA and is 2- to 2.8-fold higher than that of the normal PLGA nanoparticles. By exclusion of specific endocytosis pathways using chemical inhibitors, we found that the uptake mechanism of PVBCA-decorated nanoparticles was mainly attributed to clathrin-and-caveolae-independent endocytosis, which was distinct from that of PLGA nanoparticles. The present study provides a simple and versatile method for hepatoma-targeted delivery of nanoparticles.

PEG-g-chitosan thermosensitive hydrogel for implant drug delivery: cytotoxicity, in vivo degradation and drug release.

Thermosensitive hydrogels based on chitosan are of great interests for injectable implant drug delivery. The poly(ethylene glycol)-grafted-chitosan (PEG-g-CS) hydrogel was reported as a potential thermosensitive system. The objective of the present study is to evaluate the cytotoxicity, in vivo degradation and drug release of PEG-g-CS hydrogel. Cytotoxicity was evaluated using L929 murine fibrosarcoma cell line. Degradation and drug release in vivo were investigated by subcutaneous injection of the hydrogel into Sprague-Dawley rats. PEG-g-CS polymer exhibits no significant cytotoxicity when its concentration is less than 3 mg mL(-1). After being implanted, PEG-g-CS hydrogel maintains its integrity for two weeks and collapses, merging into the tissue, in the third week. It causes moderate inflammatory response but no fibrous encapsulation around the hydrogel is found. The hydrogel presents a three-week sustained release of cyclosporine A with no significant burst release in vitro and produces the effective drug concentration in blood for more than five weeks in vivo, performing almost the same bioavailability to chitosan/glycerophosphate hydrogel. Further modifications of PEG-g-CS hydrogel might be necessary to modulate the degradation and to mitigate the fluctuations in blood drug concentration.

Synthesis and characterization of monodispersed P(St-co-DMAEMA) nanoparticles as pH-sensitive drug delivery system.

Monodispersed poly(styrene-co-N,N'-dimethylaminoethyl methacrylate) nanoparticles (P(St-co-DMAEMA) NPs) were synthesized by emulsion polymerization. Zeta potential, volume swelling ratio and in vitro release of fluorescer coumarin-6 from the NPs were determined in buffer of various pH. With an optimized formulation, the diameter of NPs is 100 nm approximately and the polydispersity index (PI) is less than 0.1. The NPs have a hydrophilic surface and alterable surface charge which is almost neutral at normal physiological pH, but becomes much more positive under acidic conditions. The volume swelling ratios and in vitro release of coumarin-6 are highly dependent on pH, which are significantly increased at the lower pH and higher DMAEMA/St molar ratio. More than 70% of the loaded coumarin-6 could be released in 24 h at pH2, which is 2.3-folds higher than that at normal physiological pH. The P(St-co-DMAEMA) NPs show promising applications to targeted drug delivery to tumors.

Injectable chitosan-based hydrogel for implantable drug delivery: body response and induced variations of structure and composition.

Thermosensitive hydrogel composed of chitosan and glycerophosphate (CS/GP) is proposed to be the potential candidate of in situ gel-forming implant for long-term drug delivery. The present study was focused on the body response and induced structural and componential variations of the hydrogel, which were considered to impact on the drug delivery significantly but were scarcely reported. The body response was investigated by histological examination. It showed that the hydrogel caused an inflammatory response immediately after being implanted into Sprague-Dawley (SD) rats. The inflammatory response was mainly exhibited as inflammatory cell surrounding and infiltrating, tissue encapsulating, and vascularization in tissue. The effects of the inflammatory response on the structure and component of the CS/GP hydrogel were extensively explored through analyzing the hydrogel samples taken by surgery. The tissue encapsulation and osmotic pressure caused the water loss of the hydrogel and the compaction of the hydrogel network, and resulted in the porosity decreasing. The cell surrounding and infiltrating spawned big pores in the network and generated the subdivision of the network. All these structural and componential variations of the hydrogel in vivo were quite different from those in vitro and were supposed to exert significantly effects on drug release kinetics.