Citrate-Based Polyester Elastomer with Artificially Regulatable Degradation Rate on Demand.

Citrate-based polymers are commonly used to create biodegradable implants. In an era of personalized medicine, it is highly desired that the degradation rates of citrate-based implants can be artificially regulated as required during clinical applications. Unfortunately, current citrate-based polymers only undergo passive degradation, which follows a specific degradation profile. This presents a considerable challenge for the use of citrate-based implants. To address this, a novel citrate-based polyester elastomer (POCSS) with artificially regulatable degradation rate is developed by incorporating disulfide bonds (S-S) into the backbone chains of the crosslinking network of poly(octamethylene citrate) (POC). This POCSS exhibits excellent and tunable mechanical properties, notable antibacterial properties, good biocompatibility, and low biotoxicity of its degradation products. The degradation rate of the POCSS can be regulated by breaking the S-S in its crosslinking network using glutathione (GSH). After a period of subcutaneous implantation of POCSS scaffolds in mice, the degradation rate eventually increased by 2.46 times through the subcutaneous administration of GSH. Notably, we observed no significant adverse effects on its surrounding tissues, the balance of the physiological environment, major organs, and the health status of the mice during degradation.

Bulk Erosion Degradation Mechanism for Poly(1,8-octanediol-co-citrate) Elastomer: An In Vivo and In Vitro Investigation.

As a biodegradable elastomer, poly(1,8-octanediol-co-citrate) (POC) has been widely applied in tissue engineering and implantable electronics. However, the unclear degradation mechanism has posed a great challenge for the better application and development of POC. To reveal the degradation mechanism, here, we present a systematic investigation into in vivo and in vitro degradation behaviors of POC. Initially, critical factors, including chemical structures, hydrophilic and water-absorbency characteristics, and degradation reaction of POC, are investigated. Then, various degradation-induced changes during in vitro degradation of POC-x (POC with different cross-linking densities) are monitored and discussed. The results show that (1) cross-linking densities exponentially drop with degradation time; (2) mass loss and PBS-absorption ratio grow nonlinearly; (3) the morphology on the cross-section changes from flat to rough at a microscopic level; (4) the cubic samples keep swelling until they collapse into fragments from a macro view; and (5) the mechanical properties experience a sharp drop at the beginning of degradation. Finally, the in vivo degradation behaviors of POC-x are investigated, and the results are similar to those in vitro. The comprehensive assessment suggests that the in vitro and in vivo degradation of POC occurs primarily through bulk erosion. Inflammation responses triggered by the degradation of POC-x are comparable to poly(lactic acid), or even less obvious. In addition, the mechanical evaluation of POC in the simulated application environment is first proposed and conducted in this work for a more appropriate application. The degradation mechanism of POC revealed will greatly promote the further development and application of POC-based materials in the biomedical field.

Tumor-penetrating Peptide-integrated Thermally Sensitive Liposomal Doxorubicin Enhances Efficacy of Radiofrequency Ablation in Liver Tumors.

Purpose To investigate the role of a tumor-penetrating peptide (internalizing CRGDRGPDC [iRGD])-integrated thermally sensitive liposomal (TSL) doxorubicin (DOX) in combination with radiofrequency (RF) ablation of liver tumors in an animal model. Materials and Methods Approval from the institutional animal care and use committee was obtained. Characterization of iRGD-TSL-DOX was performed in vitro. Next, H22 liver adenocarcinomas were implanted in 138 mice in vivo. The DOX accumulation and cell apoptosis of iRGD-TSL-DOX and TSL-DOX with or without RF were evaluated (n = 5) at different time points after treatment with quantitative analysis or pathologic staining. Mice bearing tumors were randomized into the following six groups (each group, eight mice): no treatment, iRGD-TSL-DOX, TSL-DOX, RF alone, RF ablation followed by TSL-DOX at 30 minutes (TSL-DOX combined with RF), and RF ablation followed by iRGD-TSL-DOX (iRGD-TSL-DOX combined with RF). Kaplan-Meier method was used to estimate the survival curves and log-rank test was used for comparison with statistical software. Results DOX encapsulation efficiency in iRGD-TSL-DOX was 97.5% ± 1.3 (standard deviation) with temperature-dependent drug release capability confirmed in vitro. In vivo, the iRGD-TSL-DOX group had overall higher DOX concentration in the tumor and had maximal difference at 24 hours compared with TSL-DOX group (2.7-fold). RF caused more intense cell apoptosis at 24 hours (median, 65% vs 21%, respectively; P < .001). For end-point survival, the iRGD-TSL-DOX combined with RF group had better survival (median, 32 days) than TSL-DOX combined with RF (median, 27 days; P = .035) or RF alone (median, 21 days; P < .001). Conclusion Conjugation to iRGD helped to improve intratumoral DOX accumulation and further enhanced the activity of TSL-DOX in RF ablation of liver tumors. © RSNA, 2017 Online supplemental material is available for this article.

Tough and Water-Resistant Bioelastomers with Active-Controllable Degradation Rates.

Biodegradable electronic devices have gained significant traction in modern medical applications. These devices are generally desired to have a long enough working lifetime for stable operation and allow for active control over their degradation rates after usage. However, current biodegradable materials used as encapsulations or substrates for these devices are challenging to meet the two requirements due to the constraints of inadequate water resistance, poor mechanical properties, and passive degradation characteristics. Herein, we develop a novel biodegradable elastomer named POC-SS-Res by introducing disulfide linkage and resveratrol (Res) into poly(1,8-octanediol-co-citrate) (POC). Compared to POC, POC-SS-Res exhibits good water resistance and excellent mechanical properties in PBS, providing effective protection for devices. At the same time, POC-SS-Res offers the unique advantage of an active-controllable degradation rate, and its degradation products express low biotoxicity. Good biocompatibility of POC-SS-Res is also demonstrated. Bioelectronic components encapsulated with POC-SS-Res have an obvious prolongation of working lifetime in PBS compared to that encapsulated with POC, and its degradation rate can be actively controlled by the addition of glutathione (GSH).

Species-specific microplastic enrichment characteristics of scleractinian corals from reef environment: Insights from an in-situ study at the Xisha Islands.

The microplastic pollution has become a worldwide ecological concerns and imposed negative impacts on the coral reef ecosystems. In the present study, the distribution and characteristics of microplastics in the seawater, marine sediment and three scleractinian coral species (Pocillopora damicornis, Galaxea fascicularis, and Porites lutea) at five representative atolls in the Xisha Islands were investigated. The average microplastic abundances in the seawater and marine sediment were 9.5 ± 3.7 particles L-1 and 280.9 ± 231.9 particles kg-1 (dry weight), and the average contents of microplastics in P. damicornis, G. fascicularis and P. lutea were 0.9 ± 0.5 particles cm-2, 1.2 ± 0.6 particles cm-2, and 2.5 ± 1.6 particles cm-2, respectively. There were no significant correlations for the microplastic concentration between the reef environment and the corals. These results infer that the microplastic pollution is severe in the coral reef ecosystem in the Xisha Islands, and scleractinian corals could enrich microplastics from the reef environment. In addition, more than 80% of the microplastics in the seawater, marine sediment and corals were smaller than 2 mm, and the most common types of microplastics were cellophane (61.13%) and polyethylene terephthalate (33.49%). Black and fibers were the most common color and shape of the microplastics in the seawater and marine sediment, respectively. The microplastics in transparent color, film shape and small size (<2 mm) were highly accumulated in corals. Besides, cluster analysis showed that significant difference of microplastic characteristics existed between the corals and the reef environment, and the features of enriched microplastics among three coral species were also different. Moreover, P. lutea exhibited a stronger ability in enriching microplastics than G. fascicularis and P. damicornis. These results suggest that the microplastic-enriching capacities of scleractinian corals are species-specific, and species acclimated to microplastic pollution might become predominant in future coral community.

A bibliometric research based on hotspots and frontier trends of denosumab.

Denosumab is a monoclonal antibody that targets and inhibits the osteoclast activating factor receptor activator for nuclear factor-κB ligand (RANKL). It has been widely used in the treatment of osteoporosis, giant cell tumors of bone, and in the prevention of malignant skeletal-related events (SREs). We collected the research results and related MeSH terms of denosumab from 2011 to 2021 through the Web of Science and PubMed, respectively. The literature was visualized and analyzed by CiteSpace and bibliometric online analysis platforms. The MeSH terms were biclustered using the Bibliographic Co-Occurrence Analysis System (BICOMB) and graph clustering toolkit (gCLUTO). The results show that the number of denosumab-related annual publications had increased from 51 to 215, with the United States leading and Amgen Inc. being the most influential in the past 10 years. Articles published in the Journal of Bone and Mineral Research had the highest total citations. Three scholars from Shinshu University in Matsumoto, Yukio Nakamura, Takako Suzuki, and Hiroyuki Kato, joined the field relatively late but produced the most. The clinical comparison and combination of denosumab with other drugs in the treatment of osteoporosis was the most significant focus of research. Drug withdrawal rebound and management strategies have gained more attention and controversy recently. MeSH analysis revealed eight major categories of research hotspots. Among them, exploring the multiple roles of the RANK-RANKL-OPG system in tumor progression, metastasis, and other diseases is the potential direction of future mechanism research. It is a valuable surgical topic to optimize the perioperative drug administration strategy for internal spinal fixation and orthopedic prosthesis implantation. Taken together, the advantages of denosumab were broad and cost-effective. However, there were still problems such as osteonecrosis of the jaw, severe hypocalcemia, a high recurrence rate of giant cells in the treatment of bone and individual sarcoidosis, and atypical femoral fractures, which need to be adequately solved.

Differential enrichment and physiological impacts of ingested microplastics in scleractinian corals in situ.

Microplastics are emerging contaminants and widespread in the ocean, but their impacts on coral reef ecosystems are poorly understood, and in situ study is still lacking. In the present study, the distribution patterns of microplastics in the environment and inhabiting organisms were investigated along the east coast of Hainan Island, South China Sea, and the physiological impacts of the microplastics on scleractinian corals were analyzed. We documented average microplastic concentrations of 14.90 particlesL-1 in seawater, 343.04 particleskg-1 in sediment, 4.97 particlescm-2 in corals, and 0.67-3.12 particlescm-1 in Tridacnidae, Trochidae and fish intestines. Further analysis revealed that the characteristics of microplastics in the organisms were different from those in the environment, indicating preferential enrichment in the organisms. Furthermore, there was an obvious correlation between microplastic concentration and symbiotic density in corals. Furthermore, caspase3 activity was significantly positively correlated with the microplastic content in the small-polyp coral Pocillopora damicornis, but the large-polyp coral Galaxea fascicularis showed higher tolerance to microplastics. Taken together, our results suggest that microplastics are selectively enriched in corals and other reef-dwellers, in which they exact differential stress (apoptotic) effects, with the potential to impact the coral-Symbiodiniaceae symbiosis and alter the coral community structure.

Parallel advances in improving mechanical properties and accelerating degradation to polylactic acid.

Going up further on the basis of excellent mechanical properties and solving the long-standing shortcoming of the slow degradation rate were developed in parallel for polylactic acid (PLA). The polylactic acid/wood flour/polymethylmethacrylate (PLA/WF/PMMA) composites were prepared by melt blending used PLA as matrix, WF of diverse particle size with PMMA at 8:2 mass ratio totally filled with 20 wt%. The PLA/WF/PMMA composites were studied by means of Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), melting index test, and universal mechanical properties test. The result shows that WF of 150 µm < particle size < 180 µm executed the optimal improvement to mechanical properties of PLA/WF/PMMA. Tensile strength, flexural modulus and Young's modulus of PLA/WF/PMMA (150-180 µm) were enhanced 10.02%, 37.21% and 32.80% in relation to neat PLA, respectively. Hydrophilic contact angle test, water absorption measurement and hydrolysis assessment were performed to the hydrolysis degradation performance of materials. Furthermore, PMMA and WF cooperatively assisted in enormously accelerating hydrolysis of PLA, eventually having a good performance. Improving mechanical properties and accelerating degradation at the same time are of great significance for expanding the application of PLA.

Jointly modified mechanical properties and accelerated hydrolytic degradation of PLA by interface reinforcement of PLA-WF.

Polylactic acid (PLA), one of the most likely green and environmentally friendly materials, is an alternative to petroleum-based plastic. It still remains a challenge to increase the degradation rate and decrease the cost of PLA without compromised mechanical properties. Low cost PLA/wood flour (WF) composite was elaborately designed and fabricated with improved interface compatibility through the introducing of polymethyl methacrylate (PMMA). The result indicated that compared with that of neat PLA, the tensile strength and bending strength of PLA/WF/PMMA (8:2) (80 wt% of the PLA, 20 wt% of WF and PMMA (8:2)) were increase by 4.60% and 26.54% respectively. Through the hydrolysis experiments combined with the SEM analysis, the main reason for the improvement of the mechanical properties of composite materials was that PMMA makes continuous three-phase composition, and interface compatibility of PLA and WF with overly different polarity was modified. Meanwhile, the hydrolysis rate of PLA/WF/PMMA was much faster than that of PLA. Finally, there was a more significant discovery that the addition of PMMA changed material degradation mechanism, and it was why to efficiently accelerate the degradation rate of the material. This will provide a new inspiration for PLA degradation research, and a fresh perspective is to be given other materials.

Role of saliva proteinase 3 in dental caries.

Salivary analysis can be used to assess the severity of caries. Of the known salivary proteins, a paucity of information exists concerning the role of proteinase 3 (PR3), a serine protease of the chymotrypsin family, in dental caries. Whole, unstimulated saliva was collected from children with varying degrees of active caries and tested using a Human Protease Array Kit and an enzyme-linked immunosorbent assay. A significantly decreased concentration of salivary PR3 was noted with increasing severity of dental caries (P<0.01); a positive correlation (r=0.87; P<0.01; Pearson's correlation analysis) was also observed between salivary pH and PR3 concentration. In an antibacterial test, a PR3 concentration of 250 ng·mL⁻¹ or higher significantly inhibited Streptococcus mutans UA159 growth after 12 h of incubation (P<0.05). These studies indicate that PR3 is a salivary factor associated with the severity of dental caries, as suggested by the negative relationship between salivary PR3 concentration and the severity of caries as well as the susceptibility of S. mutans to PR3.