Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Biotransformation of Organophosphate Diesters Characterized via In Vitro Metabolism and In Vivo Screening.

Organophosphate diesters (di-OPEs), as additives in industrial applications and/or transformation products of emerging environmental pollutants, such as organophosphate triesters (tri-OPEs), have been found in the environment and biological matrices. The metabolic fate of di-OPEs in biological media is of great significance for tracing the inherent and precursor toxicity variations. This is the first study to investigate the metabolism of a suite of di-OPEs by liver microsomes and to identify any metabolite of metabolizable di-OPEs in in vitro and in vivo samples. Of the 14 di-OPEs, 5 are significantly metabolizable, and their abundant metabolites with hydroxyl, carboxyl, dealkylated, carbonyl, and/or epoxide groups are tentatively identified. More than half of the di-OPEs are detectable in human serum and/or wild fish tissues, and dibenzyl phosphate (DBzP), bis(2,3-dibromopropyl) phosphate (BDBPP), and isopropyl diphenyl phosphate (ip-DPHP) are first reported at a detectable level in humans and wildlife. Using an in vitro assay and a known biotransformation rule-based integrated screening strategy, 2 and 10 suspected metabolite peaks of DEHP are found in human serum and wild fish samples, respectively, and are then identified as phase I and phase II metabolites of DEHP. This study provides a novel insight into fate and persistence of di-OPE and confirms the presence of di-OPE metabolites in humans and wildlife.

Aerobic Microbial Transformation of Fluorinated Liquid Crystal Monomer: New Pathways and Mechanism.

Fluorinated liquid crystal monomers (FLCMs) have been suggested as emerging contaminants, raising global concern due to their frequent occurrence, potential toxic effects, and endurance capacity in the environment. However, the environmental fate of the FLCMs remains unknown. To fill this knowledge gap, we investigated the aerobic microbial transformation mechanisms of an important FLCM, 4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3, 5-difluoro-4'-propylbiphenyl (DTMDPB), using an enrichment culture termed as BG1. Our findings revealed that 67.5 ± 2.1% of the initially added DTMDPB was transformed in 10 days under optimal conditions. A total of 14 microbial transformation products obtained due to a series of reactions (e.g., reductive defluorination, ether bond cleavage, demethylation, oxidative hydroxylation and aromatic ring opening, sulfonation, glucuronidation, O-methylation, and thiolation) were identified. Consortium BG1 harbored essential genes that could transform DTMDPB, such as dehalogenation-related genes [e.g., glutathione S-transferase gene (GST), 2-haloacid dehalogenase gene (2-HAD), nrdB, nuoC, and nuoD]; hydroxylating-related genes hcaC, ubiH, and COQ7; aromatic ring opening-related genes ligB and catE; and methyltransferase genes ubiE and ubiG. Two DTMDPB-degrading strains were isolated, which are affiliated with the genus Sphingopyxis and Agromyces. This study provides a novel insight into the microbial transformation of FLCMs. The findings of this study have important implications for the development of bioremediation strategies aimed at addressing sites contaminated with FLCMs.

Establishment of a Target, Suspect, and Functional Group-Dependent Screening Strategy for Organophosphate Esters (OPEs): "Into the Unknown" of OPEs in the Sediment of Taihu Lake, China.

Current environmental monitoring studies are generally confined to several target organophosphate esters (OPEs), and there is a lack of strategies for comprehensively screening all potential OPEs in environmental samples. Here, an effective and accurate strategy was developed for the target, suspect, and functional group-dependent screening of OPEs by the use of ultrahigh-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), and this strategy was applied for the analysis of n = 74 sediment samples (including 23 surface sediment samples and 51 sediment core samples) collected from Taihu Lake (eastern China) in 2019. In these analyzed samples, we successfully identified n = 35 OPEs, and 23 of them were reported in this region for the first time. In addition, this strategy also presented other interesting findings, i.e., (1) OPE concentrations decreased with increasing distance from the coast of the lake; (2) the newly identified 3-hydroxyphenyl diphenyl phosphate (meta-OH-TPHP) was not statistically significantly correlated with triphenyl phosphate (TPHP; r = 0.02494, p = 0.9101) but with resorcinol bis(diphenyl phosphate) (RDP) (r = 0.9271, p < 0.0001) and three other OPEs; and (3) the summed concentrations of aryl OPEs (∑arylOPEs) in sediment core samples exhibited significantly increasing trends as the depth decreased. Collectively, this study provided an effective strategy that was successfully applied for comprehensive screening of OPEs in the sediments of Taihu Lake, and this strategy could have promising potential to be extended to other environmental matrices or samples.

Functional Group-Dependent Screening of Organophosphate Esters (OPEs) and Discovery of an Abundant OPE Bis-(2-ethylhexyl)-phenyl Phosphate in Indoor Dust.

There is increasing scientific interest in environmental pollution and the effect on public health caused by organophosphate esters (OPEs). Using liquid chromatography coupled to a hybrid quadrupole Orbitrap high-resolution mass spectrometer, a novel, robust, and untargeted screening strategy for the identification of novel OPEs in indoor dust samples was presently developed based on the characteristic molecular fragmentation pathways, and 12 previously reported OPEs and six previously unrecognized OPEs were detected in the combined extracts of indoor dust samples, collected in Nanjing, eastern China. One of the six detected OPEs, bis-(2-ethylhexyl)-phenyl phosphate (BEHPP), was identified by comparison of unique LC and MS characteristics with a synthesized pure standard. Accurate concentrations of BEHPP were determined in n = 50 individual indoor dust samples with 100% detection frequency with a median concentration range of 50-1530 ng/g dry weight, which were generally greater or at least comparable to traditional OPEs, that is, triphenyl phosphate and 2-ethylhexyl diphenyl phosphate (EHDPP), in the same dust samples. Statistically significant, positive correlations were found for log-transformed concentrations of BEHPP versus EHDPP (r2 = 0.7884, p < 0.0001), and BEHPP versus tris(2-ethylhexyl)phosphate (r2 = 0.4054, p < 0.0001), suggesting their similar commercial applications and sources in the environment.

Supercapsular percutaneously-assisted total hip (SuperPath) versus posterolateral total hip arthroplasty in bilateral osteonecrosis of the femoral head: a pilot clinical trial.

BACKGROUND: The supercapsular percutaneously-assisted total hip arthroplasty (SuperPath) was proposed to be minimally invasive and tissue sparing with possible superior postoperative outcomes to traditional approaches of total hip arthroplasty (THA). Here, we compared the short-term outcomes of staged THA with the SuperPath or through posterolateral approach (PLA) for bilateral osteonecrosis of the femoral head (ONFH). METHODS: Patients with bilateral late-stage ONFH were prospectively recruited from our department from March 2017 to March 2018. Staged bilateral THAs with one side SuperPath and the other side PLA were performed consecutively in the same patients with right and left hips alternating within approaches. The average time interval between the staged THAs was 3 months. Perioperative status (operation time, incision length, intraoperative blood loss, soft tissue damage, and length of hospital stay) and postoperative function (range of motion, pain, and hip function) were recorded and compared between the SuperPath and PLA approaches within 12-month postoperatively. RESULTS: Four male patients (age, 51.00 ± 4.54; BMI, 21.49 ± 1.73) with bilateral alcohol-induced ONFH (Ficat III/IV) were followed up over 12 months postoperatively. Compared with the PLA, the SuperPath yielded shorter incision length (7.62 vs. 11.12 cm), longer operation time (103.25 vs. 66.50 min), more blood loss (1108.50 vs. 843.50 ml), deficient abduction angle of the acetabular cup (38.75° vs. 44.50°), and inferior early-term hip function (Harris hip score, 72.50 vs. 83.25) at 12-month postoperatively. Soft tissue damage, length of hospital stay, postoperative pain, postoperative range of motion, and 12-month patient satisfaction were comparable between both approaches. CONCLUSION: The SuperPath may be a minimally invasive technique but the present study shows less favorable short-term outcomes than PLA for total hip arthroplasty in osteonecrosis of the femoral head. More investigations are required to provide convincing favorable evidences of the SuperPath over other traditional THA approaches. TRIAL REGISTRATION INFORMATION: The trial was retrospectively registered in https://www.researchregistry.com (No. Researchregistry4993) on July 04, 2019. The first participant was enrolled on March 13, 2017.

Comparison of oral versus intra-articular tranexamic acid in enhanced-recovery primary total knee arthroplasty without tourniquet application: a randomized controlled trial.

BACKGROUND: Although randomized controlled trials have confirmed oral tranexamic acid (TXA) can provide similar blood-sparing efficacy compared with intravenous (IV) TXA in total knee arthroplasty (TKA), some concerns do remain about thromboembolic events after such systemic administration. Many studies have confirmed that intra-articular (IA) application of TXA can show similar blood-saving efficacy with minimal levels of systemic absorption compared with IV TXA. However, it remains unclear whether the efficacy and safety of oral TXA administration is equal to or less than that of IA administration in TKA without the use of a tourniquet and drain. Thus, this study was to verify non-inferior efficacy and safety of oral TXA compared with IA TXA in primary TKA. METHODS: A double-blind, randomized, controlled trial was performed to compare three oral doses of TXA (2 g of TXA 2 h before incision, and 1 g of TXA 6 and 12 h after surgery, respectively) with IA TXA (3 g of TXA in 100 mL of saline solution). One hundred forty-seven patients scheduled for TKA were randomized to one of the two interventions. The primary outcome was total blood loss. The secondary outcomes included reduction of hemoglobin concentration, clinical outcomes, blood coagulation values, thromboembolic complications, and transfusion rates. RESULTS: The mean total blood loss was 788.8 mL in the oral TXA group compared with 872.4 mL in the IA TXA group, with no statistical significance (p > 0.05). There were no significant differences in reduction of hemoglobin level, blood coagulation level, and clinical outcomes. The transfusion rates were 4% in oral group and 5% IA group, respectively. Also, no significant differences were identified in thromboembolic complications. CONCLUSION: Oral TXA according to the described protocol demonstrated non-inferiority for primary TKA, with no safety concerns and a greatly reduced cost, compared with the IA TXA. This randomized controlled trial supports the oral administration of TXA in TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR-INR-17010968 ) dated 23rd March 2017.

[Classification and Treatment of Sacroiliac Joint Dislocation].

OBJECTIVE: To develop a renewed classification and treatment regimen for sacroiliac joint dislocation. METHODS: According to the direction of dislocation of sacroiliac joint,combined iliac,sacral fractures,and fracture morphology,sacroiliac joint dislocation was classified into 4 types. Type Ⅰ (sacroiliac anterior dislocation): main fracture fragments of posterior iliac wing dislocated in front of sacroiliac joint. Type Ⅱ (sacroiliac posterior dislocation): main fracture fragments of posterior iliac wing dislocated in posterior of sacroiliac joint. Type Ⅲ (Crescent fracturedislocation of the sacroiliac joint): upward dislocation of posterior iliac wing with oblique fracture through posterior iliac wing. Type ⅢA: a large crescent fragment and dislocation comprises no more than onethird of sacroiliac joint,which is typically inferior. Type ⅢB: intermediatesize crescent fragment and dislocation comprises between one and twothirds of joint. Type ⅢC: a small crescent fragment where dislocation comprises most,but not the entire joint. Different treatment regimens were selected for different types of fractures. Treatment for type Ⅰ sacroiliac joint dislocation: anterior iliac fossa approach pry stripping reset; sacroiliac joint fixed with sacroiliac screw through percutaneous. Treatment for type Ⅱ sacroiliac joint dislocation: posterior sacroiliac joint posterior approach; sacroiliac joint fixed with sacroiliac screw under computer guidance. Treatment for type ⅢA and ⅢB sacroiliac joint dislocation: posterior sacroiliac joint approach; sacroiliac joint fixed with reconstruction plate. Treatment for type ⅢC sacroiliac joint dislocation: sacroiliac joint closed reduction; sacroiliac joint fixed with sacroiliac screw through percutaneous. Treatment for type Ⅳ sacroiliac joint dislocation: posterior approach; sacroiliac joint fixed with spinal pelvic fixation. RESULTS: Results of 24 to 72 months patient follow-up (mean 34.5 months): 100% survival,100% wound healing,and 100% fracture healing. Two cases were identified as type Ⅰ sacroiliac joint dislocation,including one with coexistence of nerve injury. Patients recovered completely 12 months after surgery. Eight cases were identified as type Ⅱ sacroiliac joint dislocation; none had obvious nerve injury during treatments. Twelve cases were identified as type Ⅲ sacroiliac joint dislocation,including one with coexistence of nerve injury. Patients recovered completely 12 months after surgery. Three cases were identified as type Ⅳ sacroiliac joint dislocation with coexistence of nerve injury. Two patients fully recovered 12 months after surgery. One had partial recovery of neurological function. CONCLUSION: The classification and treatment regimen for sacroiliac joint dislocation have achieved better therapeutic effect,which is worth promoting.

[Vein Nerve Conduit Supported by Vascular Stent in the Regeneration of Peripheral Nerve in Rabbits].

OBJECTIVE: To evaluate the effectiveness of autologous vein nerve conduit supported by vascular stent in repairing a 10 mm gap peroneal nerve in white New Zealand rabbits. METHODS: 30 New Zealand rabbits were randomly divided into three groups: autologous nerve group (group A),conventional autologous vein nerve conduit group (group B),autologous vein nerve conduit supported by vascular stent group (group C). 10 mm common peroneal nerve was cut off. In groups A,the peroneal nerve was turned 180 ° before suturing. In group B and group C,20 mm long external jugular vein was cut and removed. After dilution of venous retraction,the venous bridge filled the gap of the nerve defect in group B. In group C,a blood vessel stent was placed for accessing the external jugular vein,and then connected to the nerve defect. Ulnar ulcer was observed after operations. Reflex score of left foot toe was recorded. The nerve regeneration and functional recovery was assessed through electrophysiological examinations,comparison of wet mass ratio between the left and right hind limb gastrocnemius,morphological observations,transmission electron microscopy 12 weeks after operations. RESULTS: Group B had the lowest scoring of toespreading reflex,whereas Group A had the highest scoring of toespreading reflex. There was a statistically significant difference in the scoring of toespreading reflex between group A and group C. In terms of the diameter of regenerated nerve fiber and the thickness of regenerated myelin sheath,no statistically significant ( P>0.05) difference was found between group A and group C,whereas the difference was significant ( P<0.05) between groups A/C and group B. The presence of peripheral nerves found in light microscopic examinations revealed normal characteristics of myelinated fibers in all groups. The myelinated axon profile was almost equal between group B and group C under electron microscopic examinations. However,more degenerated axons with disturbed contoursin were found in group B compared with group C. CONCLUSION: Autologous vein nerve conduit supported by vascular stent increases regeneration of nerves.

[Comparison of USS Combined with Sacroiliac Screw and CMAS Iliosacral Fixation in the Treatment of Unstable Sacral Fracture].

OBJECTIVE: To compare the effectiveness of two lumbopelvic fixation procedures for treating unstable sacral fractures. METHODS: The clinical data of 47 patients were treated for unstable sacral fractures in the West China Hospital of Sichuan University from January 2010 to December 2014 were reviewed. Twentytwo patients (28 sides) were treated with USS combined with iliosacral screw (group A),while 25 patients (39 sides) were treated with closed multiaxial screws (CMAS) iliosacral fixation system combined with Posterior Segmental Spinal Fixation system (group B). The outcomes of the two procedures were compared using the following indicators: length of operations,amount of intraoperative blood loss,MATTA score of fracture reduction,MAJEED function score one year postoperation,postoperative complications,and GIBBONS Classification of sacral nerve injury in patients with sacral nerve symptoms. RESULTS: Group A had longer operations [(121.4±5.1) min] than group B [(110.6±4.5) min, P<0.05]. Group A had larger intraoperative blood loss [(618±45) mL] than group B [(570±40) mL, P<0.05]. Both groups had two cases of wound infection after operations that were cured by debridement and antibiotic therapy. According to the MATTA scoring criteria,group A had 92.9% excellent and good fracture reduction,compared with 97.5% in group B ( P<0.05). According to the MAJEED functional scoring criteria,group A had 86.4% excellent and good clinical functions,compared with 92.0% in group A ( P<0.05). The GIBBONS criteria indicated that neurological functions of both groups improved significantly after operations ( P<0.05),but no significant difference appeared between the two groups ( P>0.05). CONCLUSION: CMAS iliosacral fixation system is better for treating unstable sacral fractures compared with USS combined with iliosacral screws.

A critical review on organophosphate esters in drinking water: Analysis, occurrence, sources, and human health risk assessment.

Organophosphate esters (OPEs) are ubiquitous in the environment. Copious studies assessed OPEs in various environmental media. However, there is limited summative information about OPEs in drinking water. This review provides comprehensive data for the analytical methods, occurrence, sources, and risk assessment of OPEs in drinking water. In general, liquid-liquid extraction and solid-phase extraction are the most common methods in the extraction of OPEs from drinking water, while gas chromatography and liquid chromatography are the most commonly used instrumental methods for detecting OPEs in drinking water. On the basis of these techniques, a variety of methods on OPEs pretreatment and determination have been developed to know the pollution situation of OPEs. Studies on the occurrence of OPEs in drinking water show that the total concentrations of OPEs vary seasonally and regionally, with tris(1-chloro-2-isopropyl) phosphate and tris(2-chloroethyl) phosphate dominant among different kinds of drinking water. Source identification studies show that there are three main sources of OPEs in drinking water: 1) source water contamination; 2) residual in drinking water treatment process; 3) leakage from device or pipeline. Besides, risk assessments indicate that individual and total OPEs pose no or negligible health risk to human, but this result may be significantly underestimated. Finally, the current knowledge gaps on the research of OPEs in drinking water are discussed and some suggestions are provided for future environmental research.

M2 macrophage-derived exosome-functionalized topological scaffolds regulate the foreign body response and the coupling of angio/osteoclasto/osteogenesis.

Designing scaffolds that can regulate the innate immune response and promote vascularized bone regeneration holds promise for bone tissue engineering. Herein, electrospun scaffolds that combined physical and biological cues were fabricated by anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The topological pore structure of the fiber and the immobilization of exosomes increased the nanoscale roughness and hydrophilicity of the fibrous scaffold. In vitro cell experiments showed that exosomes could be internalized by target cells to promote cell migration, tube formation, osteogenic differentiation, and anti-inflammatory macrophage polarization. The activation of fibrosis, angiogenesis, and macrophage was elucidated during the exosome-functionalized fibrous scaffold-mediated foreign body response (FBR) in subcutaneous implantation in mice. The exosome-functionalized nanofibrous scaffolds also enhanced vascularized bone formation in a critical-sized rat cranial bone defect model. Importantly, histological analysis revealed that the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. This study elaborated on the complex processes within the cell microenvironment niche during fibrous scaffold-mediated FBR and vascularized bone regeneration to guide the design of implants or devices used in orthopedics and maxillofacial surgery. STATEMENT OF SIGNIFICANCE: How to design scaffold materials that can regulate the local immune niche and truly achieve functional vascularized bone regeneration still remain an open question. Here, combining physical and biological cues, we proposed new insight to cell-free and growth factor-free therapy, anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The exosomes functionalized-scaffold system mitigated foreign body response, including excessive fibrosis, tumor-like vascularization, and macrophage activation. Importantly, the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation.

Plastic packaging-associated chemicals and their hazards - An overview of reviews.

Plastic packaging contains residues from substances used during manufacturing, such as solvents, as well as non-intentionally added substances (NIAS), such as impurities, oligomers, or degradation products. By searching peer-reviewed literature, we found that at least 10,259 chemicals were related to plastic packaging materials, which include chemicals used during manufacturing and/or present in final packaging items. We then summarized and discussed their chemical structures, analytical instruments, migration characteristics, and hazard categories where possible. For plastic packaging chemicals, examination of the literature reveals gas and liquid chromatography hyphenated to a variety of accurate mass analyzers based on the use of high-resolution mass spectrometry is usually used for the identification of unknown migrants coming from plastic packaging. Chemical migration from food packaging is affected by several parameters, including the nature and complexity of the food, contact time, temperature of the system, type of packaging contact layer, and properties of the migrants. A review of the literature reveals that information on adverse effects is only available for approximately 1600 substances. Among them, it appears that additives are more toxic than monomers to wildlife and humans. Neurotoxicity accounted for the highest proportion of toxicity of all types of chemicals, while benzenoids, organic acids, and derivatives were the most toxic types of chemicals. Furthermore, studies have demonstrated that hydrocarbon derivatives, organic nitrogen compounds, and organometallic compounds have the highest proportions of dermatotoxicity, and organohalogen compounds have the highest proportions of hepatotoxicity. The main contributors to skin sensitization are organic salts. This study provides a basis for comprehensively publicizing information on chemicals in plastics, and could be helpful to better understand their potential risks to the environment and humans.

Organophosphate esters (OPEs) in plastic food packaging: non-target recognition, and migration behavior assessment.

Organophosphate esters (OPEs) are widely used as plasticizers in plastic food packaging; however, the migration of OPEs from plastic to food is largely unstudied. We do not even know the specific number of OPEs that exist in the plastic food packaging. Herein, an integrated target, suspect, and nontarget strategy for screening OPEs was optimized using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). The strategy was used to analyze 106 samples of plastic food packaging collected in Nanjing city, China, in 2020. HRMS allowed full or tentative identification of 42 OPEs, of which seven were reported for the first time. Further, oxidation products of bis(2,4-di-tert-butylphenyl) pentaerythritol diphosphite (AO626) in plastics were identified, implying that the oxidation of organophosphite antioxidants (OPAs) could be an important indirect source of OPEs in plastics. The migration of OPEs was examined with four simulated foods. Twenty-six out of 42 OPEs were detected in at least one of the four simulants, particularly isooctane, in which diverse OPEs were detected at elevated concentrations. Overall, the study supplements the list of OPEs that humans could ingest as well as provides essential information regarding the migration of OPEs from plastic food packaging to food.

Covalent organic frameworks bearing Ni active sites for free radical-mediated photoelectrochemical organic transformations.

Photoelectrochemical (PEC) organic transformations occurring at anodes are a promising strategy for circumventing the sluggish kinetics of the oxygen evolution reaction. Here, we report a free radical-mediated reaction instead of direct hole transfer occurring at the solid/liquid interface for PEC oxidation of benzyl alcohol (BA) to benzaldehyde (BAD) with high selectivity. A bismuth vanadate (BiVO4) photoanode coated with a 2,2'-bipyridine-based covalent organic framework bearing single Ni sites (Ni-TpBpy) was developed to drive the transformation. Experimental studies reveal that the reaction at the Ni-TpBpy/BiVO4 photoanode followed first-order reaction kinetics, boosting the formation of surface-bound ·OH radicals, which suppressed further BAD oxidation and provided a nearly 100% selectivity and a rate of 80.63 µmol hour-1 for the BA-to-BAD conversion. Because alcohol-to-aldehyde conversions are involved in the valorizations of biomass and plastics, this work is expected to open distinct avenues for producing key intermediates of great value.

A Biocompatible Self-Powered Piezoelectric Poly(vinyl alcohol)-Based Hydrogel for Diabetic Wound Repair.

Acute and chronic wounds, caused by trauma, tumors, diabetic foot ulcers, etc., are usually difficult to heal, while applying exogenous electrical stimulation to enhance the endogenous electric field in the wound has been proven to significantly accelerate wound healing. However, traditional electrical stimulation devices require an additional external power supply, making them poor in portability and comfort. In this work, a self-powered piezoelectric poly(vinyl alcohol) (PVA)/polyvinylidene fluoride (PVDF) composite hydrogel is constructed by establishing a distinctive preparation process of freezing/thawing-solvent replacement-annealing-swelling. The hydrogen bonding in the hydrogel is remarkably enhanced by the annealing-swelling process, which is stronger between PVA/PVDF molecules than that between PVA molecules, promoting transformation of the α-phase into the electroactive ß-phase PVDF and facilitating formation of a much more crystalline structure with high cross-linking density. Hence, an obvious piezoelectric response with high piezoelectric coefficient and electrical signal output with superior stability and sensitivity and excellent mechanical strength and stretchability was achieved for hydrogels. PVA/PVDF composite hydrogels with good cytocompatibility significantly promote proliferation, migration, and secretion of extracellular matrix proteins and growth factors of fibroblasts, possibly through activating the AKT and ERK1/2 signaling pathways. In a wound model of diabetic rats, piezoelectric hydrogels could not only rapidly attract wound exudate and maintain the wet environment of the wound bed but also convert the mechanical energy generated by rats' physical activities into electrical energy, so as to provide local piezoelectric stimulation to the wound bed evenly and symmetrically in real time. Such an effect significantly promotes re-epithelialization and collagen deposition and increases angiogenesis and secretion of growth factors in wound tissue. Besides, it regulates the macrophage phenotype from the M1 subtype (pro-inflammatory subtype) to the M2 subtype (anti-inflammatory subtype) and reduces the expression levels of inflammatory factors, thus accelerating wound healing. The development of such a novel piezoelectric hydrogel provides new therapeutic strategies for chronic wound healing.

First insight on in vitro metabolism of three newly identified aryl organophosphate esters via a suspect coupled with nontarget screening approach.

The ubiquity of organophosphate esters (OPEs) in the environment has triggered research into metabolic pathways of OPEs. Using liquid chromatography coupled with a hybrid quadrupole Orbitrap high-resolution mass spectrometer, a suspect and characteristic fragment ion-based nontarget screening strategy for the identification of unknown OPE metabolites was developed and evaluated. Then, this integrated approach was successfully used for investigation of three newly identified organophosphate esters (NOPEs), namely 2-biphenylol diphenyl phosphate (BPDPP), tris(2-biphenyl) phosphate (TBPHP), and naphthalen-2-yl diphenyl phosphate (NDPHP), in human liver microsomes (HLMs). The results demonstrated that BPDPP, TBPHP, and NDPHP were effectively metabolized by HLMs, with zero-order kinetics (R2 = 0.48-0.94) within the time frame of the assay. The suspected approach identified a considerable number of dearylated phosphate (DP), and hydroxylated metabolites for each of NOPEs after incubation with HLMs for 2 h. In addition, the nontarget approach further identified 9 novel metabolites including 2 epoxide intermediates and 7 oxidative ring-opening compounds, which were first reported in the Phase I metabolism of OPEs. Collectively, this study provided a novel suspect coupled with nontarget screening approach and was successfully used to screen metabolites of three NOPEs. For the first time, we observed direct evidence that oxidative ring-opening might serve as another primary metabolic pathway regarding the metabolism of aryl OPEs.

Newly discovered bis-(2-ethylhexyl)-phenyl phosphate (BEHPP) was a ubiquitous contaminant in surface soils from a typical region, South China.

The organophosphate ester (OPE), bis-(2-ethylhexyl)-phenyl phosphate (BEHPP), was recently identified as an abundant contaminant in indoor dust samples; however, its pollution status in other matrices remains unknown. Here, n = 95 surface soil samples were collected from a prefecture-level city (hereafter referred to as D city) in South China during 2019, and further analyzed to accurately determine the concentrations of BEHPP and eight other OPEs, including tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-isopropyl) phosphate (TDCIPP), triphenyl phosphate (TPHP), tris(2-butoxyethyl) phosphatetris (TBOEP), 2-ethylhexyl diphenyl phosphate (EHDPP), tris(2-ethylhexyl) phosphate (TEHP), 4-biphenylol diphenyl phosphate (BPDPP), and tris(2-biphenyl) phosphate (TBPHP). BEHPP was detected in all six functional areas (agricultural, scenic, commercial, industrial, and residential areas) of this region, and exhibited a high detection frequency of 67.4%, with a median concentration of 0.455 ng/g dry weight (DW range: nd-7.05 ng/g dw), regardless of the functional area. Samples from commercial, industrial, and residential areas contained significantly greater BEHPP concentrations than those from agricultural and scenic areas. Furthermore, strong and statistically significant correlations were observed between BEHPP and other OPE congeners, particularly for TEHP (r = 0.764, p < 0.001), TBOEP (r = 0.687, p < 0.001), and TPHP (r = 0.709, p < 0.001), indicating that BEHPP may have similar commercial applications and sources to these compounds in surface soil. Collectively, this study provides the first evidence of the presence of BEHPP in soil samples, and indicates that this emerging contaminant is widely distributed across all five functional areas of a typical region (South China).

Supercapsular percutaneously-assisted total hip (SuperPath) versus mini-incision posterolateral total hip arthroplasty for hip osteoarthritis: a prospective randomized controlled trial.

BACKGROUND: Supercapsular percutaneously-assisted total hip (SuperPath) arthroplasty has been proposed to be minimally invasive and tissue sparing, with possible superior postoperative outcomes compared with conventional approaches for total hip arthroplasty (THA). However, previous studies have underlined the shortcomings of conventional THA approaches, including higher dislocation, more blood loss, longer incisions, more tissue damage, and delayed postoperative rehabilitation. In the present study, we compared the short-term outcomes of unilateral THA with those of SuperPath and the mini-incision posterolateral approach (PLA) for hip osteoarthritis (OA). METHODS: Patients with unilateral hip OA were prospectively recruited and underwent either SuperPath (SuperPath group) or mini-incision PLA THA (PLA group). Perioperative status [operative time, incision length, intraoperative blood loss, soft tissue damage, and length of hospital stay (LOS)], and postoperative function outcomes, including range of motion (ROM), pain visual analog scale (VAS), and Harris Hip Score (HHS), were evaluated and compared between the groups at scheduled time points within 12 months postoperatively. RESULTS: Compared with the PLA group, the SuperPath group yielded a significantly shorter incision length (7.83 vs. 12.45 cm, P<0.001), longer operative time (102.72 vs. 66.22 min, P<0.001), more blood loss (1,007.38 vs. 844.55 mL, P=0.005), and more soft tissue damage (creatine kinase: 1,056.05 vs. 821.50 U/L, P=0.006) on postoperative day 3. The SuperPath group also showed deficient acetabular cup positioning (abduction angle: 36.94° vs. 42.66°, P=0.004) and a greater decrease in ROM (flexion: 107.66° vs. 114.44°, P=0.004; 109.83° vs. 116.11°, P=0.002; 111.66° vs. 118.88°, P<0.001) on postoperative days 1, 3, and 14, as well as severe early-term pain symptoms (pain VAS on postoperative day 3: 7.05 vs. 6.55, P=0.041). However, the LOS, C-reactive protein levels, erythrocyte sedimentation rate (within 2 weeks postoperatively), and HHS were comparable between the groups during the 12 months postoperatively. CONCLUSIONS: SuperPath may be a promising, minimally invasive technique for the treatment of OA in the future. Further investigation is necessary to evidence the possible superiority of SuperPath over other conventional mini-incision THA approaches.

pNaSS-Grafted PCL Film-Guided rAAV TGF-ß Gene Therapy Activates the Chondrogenic Activities in Human Bone Marrow Aspirates.

Scaffold-guided viral gene therapy is a novel, powerful tool to enhance the processes of tissue repair in articular cartilage lesions by the delivery and overexpression of therapeutic genes in a noninvasive, controlled release manner based on a procedure that may protect the gene vehicles from undesirable host immune responses. In this study, we examined the potential of transferring a recombinant adeno-associated virus (rAAV) vector carrying a sequence for the highly chondroregenerative transforming growth factor beta (TGF-ß), using poly(ɛ-caprolactone) (PCL) films functionalized by the grafting of poly(sodium styrene sulfonate) (pNaSS) in chondrogenically competent bone marrow aspirates as future targets for therapy in cartilage lesions. Effective overexpression of TGF-ß in the aspirates by rAAV was achieved upon delivery using pNaSS-grafted and ungrafted PCL films for up to 21 days (the longest time point evaluated), with superior levels using the grafted films, compared with respective conditions without vector coating. The production of rAAV-mediated TGF-ß by pNaSS-grafted and ungrafted PCL films significantly triggered the biological activities and chondrogenic processes in the samples (proteoglycan and type-II collagen deposition and cell proliferation), while containing premature mineralization and hypertrophy relative to the other conditions, with overall superior effects supported by the pNaSS-grafted films. These observations demonstrate the potential of PCL film-assisted rAAV TGF-ß gene transfer as a convenient, off-the-shelf technique to enhance the reparative potential of the bone marrow in patients in future approaches for improved cartilage repair.