Study on the Relationship and Predictive Value of First-Trimester Pregnancy-Associated Plasma Protein-A, Maternal Factors, and Biochemical Parameters in Gestational Diabetes Mellitus: A Large Case-Control Study in Southern China Mothers.

Objective: To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers. Methods: This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free ß-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11-13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24-28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test. Results: GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53-0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68-0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P<0.001). Conclusion: A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.

On-Off Phagocytosis and Switchable Macrophage Activation Stimulated with NIR for Infected Percutaneous Tissue Repair of Polypyrrole-Coated Sulfonated PEEK.

Intelligent control of the immune response is essential for obtaining percutaneous implants with good sterilization and tissue repair abilities. In this study, polypyrrole (Ppy) nanoparticles enveloping a 3D frame of sulfonated polyether ether ketone (SP) surface are constructed, which enhance the surface modulus and hardness of the sulfonated layer by forming a cooperative structure of simulated reinforced concrete and exhibit a superior photothermal effect. Ppy-coated SP could quickly accumulate heat on the surface by responding to 808 nm near-infrared (NIR) light, thereby killing bacteria, and destroying biofilms. Under NIR stimulation, the phagocytosis and M1 activation of macrophages cultured on Ppy-coated SP are enhanced by activating complement 3 and its receptor, CD11b. Phagocytosis and M1 activation are impaired along with abolishment of NIR stimulation in the Ppy-coated SP group, which is favorable for tissue repair. Ppy-coated SP promotes Collagen-I, vascular endothelial growth factor, connective tissue growth factor, and α-actin (Acta2) expression by inducing M2 polarization owing to its higher surface modulus. Overall, Ppy-coated SP with enhanced mechanical properties could be a good candidate for clinical percutaneous implants through on-off phagocytosis and switchable macrophage activation stimulated with NIR.

Chitosan@Puerarin hydrogel for accelerated wound healing in diabetic subjects by miR-29ab1 mediated inflammatory axis suppression.

Wound healing is one of the major global health concerns in patients with diabetes. Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes. miR-29ab1 plays a critical role in diabetes-related macrophage inflammation. Hence, inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing. In this study, the traditional Chinese medicine, puerarin, was introduced to construct an injectable and self-healing chitosan@puerarin (C@P) hydrogel. The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis, which were related to the inhibition of the miR-29 mediated inflammation response. Compared to healthy subjects, miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model, accompanied by upregulated M1-polarization, and elevated levels of IL-1ß and TNF-α. Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation. The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response. Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.

Puerarin@Chitosan composite for infected bone repair through mimicking the bio-functions of antimicrobial peptides.

It is important to eliminate lipopolysaccharide (LPS) along with killing bacteria in periprosthetic joint infection (PJI) therapy for promoting bone repair due to its effect to regulate macrophages response. Although natural antimicrobial peptides (AMPs) offer a good solution, the unknown toxicity, high cost and exogenetic immune response hamper their applications in clinic. In this work, we fabricated a nanowire-like composite material, named P@C, by combining chitosan and puerarin via solid-phase reaction, which can finely mimic the bio-functions of AMPs. Chitosan, serving as the bacteria membrane puncture agent, and puerarin, serving as the LPS target agent, synergistically destroy the bacterial membrane structure and inhibit its recovery, thus endowing P@C with good antibacterial property. In addition, P@C possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation modulation. The in vivo results show that P@C can inhibit the LPS induced bone destruction in the Escherichia coli infected rat. P@C exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property, and its ability of LPS elimination and immunomodulation. P@C can well mimic the functions of AMPs, which provides a novel and effective method for treating the PJI in clinic.

Association between isolated maternal hypothyroxinemia during the first trimester and adverse pregnancy outcomes in Southern Chinese women: a retrospective study of 7051 cases.

BACKGROUND: The association between isolated maternal hypothyroxinemia (IMH) and adverse pregnancy outcomes is still controversial. This study aimed to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes in southern Chinese women. METHODS: This was a hospital-based, retrospective cohort study. The records of 7051 women, including 1337 IMH women and 5714 euthyroid women who had a singleton pregnancy and accepted routine prenatal service at the Third Affiliated Hospital of Sun Yat-Sen University from January 2015 to September 2018, were extracted from the electronic medical records system in this study. Thyroid functions [thyroid-stimulating hormone (TSH), free thyroxine (fT4) and anti-thyroperoxidase autoantibody (TPO-Ab)] had to be measured before 13 weeks and 6 days of gestation. The chi-square test and multivariate logistic regression analysis were applied to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes. RESULTS: Prepregnancy obesity [prepregnancy body mass index (preBMI) ≥ 25 kg/m2] was found to be more common in the IMH group (11.2% vs. 6.1%) (P < 0.05). The prevalence of gestational diabetes mellitus (GDM), postpartum haemorrhage (PPH), macrosomia and large for gestational age (LGA) was higher in the IMH group. However, after using multivariate logistic regression analysis to adjust for confounders (maternal age, educational levels and preBMI), only LGA was shown to be associated with an increased risk in IMH women [adjusted OR: 1.27 (95% CI 1.044-1.566)]. The prevalence of preterm delivery (either < 37 or < 34 weeks), gestational hypertension, preeclampsia, placenta previa, placental abruption, premature rupture of membrane (PROM), intrauterine growth restriction (IUGR), polyhydramnios, stillbirth, small for gestational age (SGA) and low Apgar score did not increase. CONCLUSION: IMH during the first trimester did not increase any risk of adverse pregnancy outcomes in southern Chinese women except LGA.

A multifunctional cascade bioreactor based on a layered double oxides composite hydrogel for synergetic tumor chemodynamic/starvation/photothermal therapy.

The field of nanomedicine-catalyzed tumor therapy has achieved a lot of progress; however, overcoming the limitations of the tumor microenvironment (TME) to achieve the desired therapeutic effect remains a major challenge. In this study, a nanocomposite hydrogel (GH@LDO) platform combining the nanozyme CoMnFe-layered double oxides (CoMnFe-LDO) and natural enzyme glucose oxidase (GOX) was engineered to remodel the TME to enhance tumor catalytic therapy. The CoMnFe-LDO is a nanozyme that can convert endogenous H2O2 into reactive oxygen species (ROS) and O2 to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Meanwhile, GOX can catalyze the conversion of glucose and O2 to gluconic acid and H2O2, which not only represses the ATP production of tumor cells to achieve starvation therapy (ST), but also decreases the pH value of TME and supplies extra H2O2 to enhance the CDT effect. Furthermore, this well-designed CoMnFe-LDO possessed a high photothermal conversion efficiency of GH@LDO (66.63%), which could promote the generation of ROS to enhance the CDT effect and achieve photothermal therapy (PTT) under near-infrared light irradiation. The GH@LDO hydrogel performes cascade reaction which overcomes the limitation of the TME and achieves satisfactory CDT/ST/PTT synergetic effects in vitro and in vivo. This work provides a new strategy for remodeling the TME using nanomedicine to achieve precise tumor cascaded catalytic therapy. STATEMENT OF SIGNIFICANCE: At present, the focus of tumor therapy has begun to shift from monotherapy to combination therapy for improving the overall therapeutic effect. In this study, we synthesized a CoMnFe-LDO nanozyme composed of multiple transition metal oxides, which demonstrated improved peroxidase and oxidase activities as well as favorable photothermal conversion capability. The CoMnFe-LDO nanozyme was compounded with an injectable GH hydrogel crosslinked by GOX and horseradish peroxidase (HRP). This nanocomposite hydrogel overcame the limitations of weak acidity, H2O2, and O2 levels in the TME and achieved synergetic CDT, ST, and PTT effects based on the cascaded catalytic actions of CoMnFe-LDO and GOX to H2O2 and glucose.

Immunomodulation Effect of Biomaterials on Bone Formation.

Traditional bone replacement materials have been developed with the goal of directing the osteogenesis of osteoblastic cell lines toward differentiation and therefore achieving biomaterial-mediated osteogenesis, but the osteogenic effect has been disappointing. With advances in bone biology, it has been revealed that the local immune microenvironment has an important role in regulating the bone formation process. According to the bone immunology hypothesis, the immune system and the skeletal system are inextricably linked, with many cytokines and regulatory factors in common, and immune cells play an essential role in bone-related physiopathological processes. This review combines advances in bone immunology with biomaterial immunomodulatory properties to provide an overview of biomaterials-mediated immune responses to regulate bone regeneration, as well as methods to assess the bone immunomodulatory properties of bone biomaterials and how these strategies can be used for future bone tissue engineering applications.

Mechanical Force Induced Self-Assembly of Chinese Herbal Hydrogel with Synergistic Effects of Antibacterial Activity and Immune Regulation for Wound Healing.

Skin wounds, especially infected chronic wounds, have attracted worldwide attention due to the high prevalence and poor treatment outcomes. Hydrogel dressings with antibacterial ability and immune regulation property are urgently required. Herein, inspired by the grinding treatment of traditional Chinese medicine, mechanical force is introduced to promote the effective molecular collision and accelerate the self-assembly of chitosan (CS) and puerarin (PUE) for fabricating Chinese-herb-based hydrogels. The antibacterial rate of CS@PUE (C@P) hydrogel is more than 95%, and the wound closed rate is twice that of the control group. Interestingly, the rational design of C@P hydrogels with different PUE ratios enables a refined control over hydrogel formation, nanofiber appearance, viscoelastic, physicochemical, and biological properties. The extraordinary antibacterial ability of C@P hydrogels may originate from the nanofiber structure and the improved zeta potential on account of the orientation of amino groups in CS . Thus, the synergistically antibacterial and immune regulation properties of C@P hydrogels kill bacteria and relieve inflammation in the wound bed, ensuring the anti-infection effect, and boosting wound healing. In addition to providing a universal mechanosynthesis of PUE-based hydrogel for wound healing, this finding is expected to increase the attention paid to Chinese herbal medicines in the construction of biomaterials.

Hydroxyapatite composited PEEK with 3D porous surface enhances osteoblast differentiation through mediating NO by macrophage.

The adverse immune response mediated by macrophages is one of the main factors that are prone to lead poor osseointegration of polyetheretherketone (PEEK) implants in clinic. Hence, endowing PEEK with immunomodulatory ability to avoid the adverse immune response becomes a promising strategy to promote bone repair. In this work, sulfonation and hydrothermal treatment were used to fabricate a 3D porous surface on PEEK and hydroxyapatite (HA) composited PEEK. The HA composited PEEK with 3D porous surface inhibited macrophages polarizing to M1 phenotype and downregulated inducible nitric oxide synthase protein expression, which led to a nitric oxide concentration reduction in culture medium of mouse bone marrow mesenchymal stem cells (mBMSCs) under co-culture condition. The decrease of nitric oxide concentration could help to increase bone formation-related OSX and ALP genes expressions and decrease bone resorption-related MMP-9 and MMP-13 genes expressions via cAMP-PKA-RUNX2 pathway in mBMSCs. In summary, the HA composited PEEK with 3D porous surface has the potential to promote osteogenesis of PEEK through immunomodulation, which provides a promising strategy to improve the bone repair ability of PEEK.

miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone.

Coordination between osteogenesis and angiogenesis is required for bone homeostasis. Here, we show that miR-29cb2 is a bone-specific miRNA and plays critical roles on angiogenesis-osteogenesis coupling during bone remodeling. Mice with deletion of miR-29cb2 exhibit osteopenic phenotypes and osteoblast impairment, accompanied by pronounced decreases in specific H vessels. The decrease in bone miR-29cb2 was associated with pathological ovariectomy stimuli. Mechanistically, hypoxia-inducible factor (HIF)-3α, as a target for miR-29cb2, inhibits HIF-1α activity by competitively bonding with HIF-1ß. Notably, miR-29cb2 in peripheral blood (PB) nearly is undetectable in sham and significantly increases in ovariectomy mice. Further evaluation from osteoporosis patients demonstrates similar signatures. ROC analysis shows miR-29cb2 in PB has higher sensitivity and specificity for diagnosing osteoporosis when compared with four clinical biomarkers. Collectively, these findings reveal that miR-29cb2 is essential for bone remodeling by inhibiting HIF-3α and elevated bone-specific miR-29cb2 in PB, which may be a promising biomarker for bone loss.

A Novel Stimuli-Responsive Injectable Antibacterial Hydrogel to Achieve Synergetic Photothermal/Gene-Targeted Therapy towards Uveal Melanoma.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli-responsive drug delivery antibacterial hydrogel (CP@Au@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel-sol transformation to release the gene-targeted drug DC_AC50 on demand in response to low-density near-infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of CP@Au@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene-targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the CP@Au@DC_AC50+NIR group and normal group. This NIR light-triggered gene-targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM.

Strontium ranelate incorporated 3D porous sulfonated PEEK simulating MC3T3-E1 cell differentiation.

Polyetheretherketone (PEEK) has been used as an implant material because it has similar mechanical properties to natural bone. However, inferior osseointegration and bioinertness hamper the clinical application of PEEK. In this study, the surfaces of sulfonated three-dimensional (3D) PEEK porous structures were loaded with different concentrations of strontium ranelate, a compound commonly used in the treatment or prevention of osteoporosis by promoting bone formation and inhibiting bone resorption. Field-emission scanning electron microscopy was used to characterize the topography of the structures, elemental carbon, oxygen and strontium contents were measured by X-ray photoelectron spectroscopy, and surface zeta potentials and water-contact angle were also measured. The results indicated that strontium ranelate was successfully loaded onto the 3D porous structures. In vitro cellular results showed that strontium ranelate-treated sulfonated PEEK (SP-SR) strengthened the adhesion of MC3T3-E1 cells. The activity of alkaline phosphatase, collagen secretion and extracellular matrix mineralization deposition of MC3T3-E1 cells were also improved on the surface of SP-SR. These results indicate that SP-SR could serve a new implant candidate for surgical treatment.

Supraciliary Incision as a New Double-Eyelid Approach for Asian Patients: Clinical Experience of 528 Cases.

BACKGROUND: The double-eyelid operation is the most requested cosmetic surgery in Asians. The incision is usually located at the pretarsal skin 6 mm to 8 mm above palpebral margin. The purpose of this paper is to report a novel approach of double-eyelid operation through a supraciliary incision (SCI). METHODS: Three transverse curved lines were drawn on the upper lid skin. The location of line 1 (SCI) was 1.5 mm above the eyelash, line 2 according to the amount of redundant skin excised and line 3 at 3 mm to 4 mm above line 2. After the incisions were made between line 1 and line 2, the subcutaneous dissection is carried out over 5 mm the line 3. Then, the redundant skin and a strip orbicularis oculi muscle were removed to open the orbital septum and to explore underside levator aponeurosis. Along the line 3, the internal buried fixation sutures between dermal tissue and the fusion line of the orbital septum and levator aponeurosis were placed. Finally, the wounds were closed between line 2 and line 1. RESULTS: There were 528 patients who underwent the double-eyelid operation through the supraciliary approach. In long-term follow-up, 288 patients were evaluated at 6 months to 78 months postoperatively. Of those, 266 patients were satisfactory for the result (92.36%) with natural shape and invisible surgical scar. In another 22 patients (7.63%), a revised blepharoplasty was performed in 22 eyelids. CONCLUSION: The double-eyelid surgery using the SCI has several advantages including less visibility of the incision, the protected subdermal vascular network, the intact continuity of the upper eyelid skin, the combination of the SCI and internal dermal buried suture method. The approach can be considered an efficient technique for Asian patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sodium butyrate-modified sulfonated polyetheretherketone modulates macrophage behavior and shows enhanced antibacterial and osteogenic functions during implant-associated infections.

Prevention of implant-associated infections and insufficient bone tissue integration is critical to exploit the immunomodulatory properties and antibacterial effects of implant materials, which have attracted considerable attention. Modulation of the functions of immune cells in different environments is crucial for managing infection and inferior bone integration via immunomodulation. In this work, sodium butyrate, a fermentation product of gut microbiota, was loaded onto 3D porous sulfonated polyetheretherketone (SP) to modulate the immune responses of cells in different environments. Evaluation of in vitro antibacterial effects showed that sodium butyrate-loaded SP exhibited superior antibacterial activity, especially in the samples containing high concentrations of sodium butyrate. Under bacterial stimulation, the phagocytic activity of macrophages increased with an increase in the sodium butyrate concentration via the production of reactive oxygen species (ROS), which favoured bactericidal activity in the implant-associated infection stage. For bacterial elimination, sodium butyrate-containing SP could polarize macrophages to the M2 phenotype and subsequently stimulate anti-inflammatory cytokine secretion, which is considered beneficial for bone regeneration in the tissue repair stage. In vitro osteogenesis was evaluated and the results demonstrated that treatment with sodium butyrate-containing SP increased the expression of osteogenic genes and proteins. An in vivo rat osteomyelitis model was used to evaluate the protective effect of the SP-loaded with sodium butyrate on bone destruction and osteolysis under infection conditions. To study osteogenesis in vivo, a rat femoral model without infection was used. The results indicated that the SP-B2 group exhibited superior anti-infection capacity and induced new bone formation around the implant in vivo. Treatment with sodium butyrate-containing porous SP modulated the macrophage response under different stimuli, thereby serving as a new approach for the design of smart implant materials with superior antibacterial and bone repair properties.

Nanostructural Surfaces with Different Elastic Moduli Regulate the Immune Response by Stretching Macrophages.

A proper immune response is key for the successful implantation of biomaterials, and designing and fabricating biomaterials to regulate immune responses is the future trend. In this work, three different nanostructures were constructed on the surface of titanium using a hydrothermal method, and through a series of in vitro and in vivo experiments, we found that the aspect ratio of nanostructures can affect the elastic modulus of a material surface and further regulate immune cell behaviors. This work demonstrates that nanostructures with a higher aspect ratio can endow a material surface with a lower elastic modulus, which was confirmed by experiments and theoretical analyses. The deflection of nanostructures under the cell adsorption force is a substantial factor in stretching macrophages to enhance cell adhesion and spreading, further inducing macrophage polarization toward the M1 phenotype and leading to intense immune responses. In contrast, a nanostructure with a lower aspect ratio on a material surface leads to a higher surface elastic modulus, making deflection of the material difficult and creating a surface that is not conducive to macrophage adhesion and spreading, thus reducing the immune response. Moreover, molecular biology experiments indicated that regulation of the immune response by the elastic modulus is primarily related to the NF-κB signaling pathway. These findings suggest that the immune response can be regulated by constructing nanostructural surfaces with the proper elastic modulus through their influence on cell adhesion and spreading, which provides new insights into the surface design of biomaterials.

Pravastatin regulates host foreign-body reaction to polyetheretherketone implants via miR-29ab1-mediated SLIT3 upregulation.

Host rejection to biomaterials can induce uncontrolled foreign-body reactions (FBR), resulting in a dense fibrous encapsulation that blocks mass transport and/or communication between the host and the implant. Adequate angiogenesis between the body and the implant has been implicated as a key regulator for overcoming FBR. Thus, approaches for stimulating neovascularization and/or suppressing FBR are under investigation. In this study, pravastatin (Pra) was loaded onto a 3D network surface of sulfonated polyetheretherketone (SP) to achieve superior local drug effects. The SP loaded with Pra (SP-Pra) promoted angiogenesis and mitigated FBR via miR-29 dependent SLIT3 upregulation in wild-type (WT) mice. miR-29a and miR-29b1 were significantly downregulated in the SP-Pra capsule compared to levels in the SP capsule, while SLIT3 and neovascularization were substantially upregulated in WT mice. However, the above effects presented in the WT mice were not detected in miR-29ab1 knockout mice which was generated by the CRISPR/Cas9 approach. Overall, the results suggest that miR-29 plays a critical role in reducing FBR to these implants by targeting SLIT3. Suppression of FBR by SP-Pra implants offers the potential to improve the performance of current medical devices.

Multifunctional sulfonated polyetheretherketone coating with beta-defensin-14 for yielding durable and broad-spectrum antibacterial activity and osseointegration.

To address periprosthetic joint infection (PJI), a formidable complication after joint arthroplasty, an implant with excellent osseointegration and effective antibacterial activity has being extensively pursued and developed. In this work, the mouse beta-defensin-14 (MBD-14) was immobilized on the polyetheretherketone (PEEK) surface with three-dimensional (3D) porous structure to improve its antibacterial activity and osseointegration. An in vitro antibacterial evaluation showed that the porous PEEK loaded with MBD-14 wages a durable and effective fight against both Staphylococcus aureus (gram-positive) and Pseudomonas aeruginosa (gram-negative). In addition to the superior antibacterial activity, we found that the enhanced proliferation and osteogenic differentiation of bone mesenchymal stem cells were verified through various in vitro analyses. To evaluate the in vivo bactericidal effect and osseointegration of the samples, the rat femoral models with infection and non-infection were established. The enhanced osseointegration of the MBD-14-loaded samples was found in both two in vivo models. And no bacteria survived on the surfaces of samples with a relatively high MBD-14 concentration. Above results indicate that the 3D porous PEEK coating loaded with MBD-14 simultaneously yields excellent osseointegration while exerting durable and broad-spectrum antibacterial activity. And it paves the way for PEEK to be applied clinically to address PJI. STATEMENT OF SIGNIFICANCE: (1). By using the physio-chemical technique including sulfonation and lyophilization etc., a three-dimensional porous network is developed on polyetheretherketone (PEEK) surface, in which mouse beta-defensin-14 (MBD-14, a broad-spectrum antimicrobial peptide) is then loaded. It endows PEEK with antibacterial activity and osseointegration. (2). Two in vivo animal models with infection and non-infection are used to prove the new bone formation around the samples. (3). Supplementary material also proves that MBD-14 promotes the osteogenic differentiation of BMSCs. However, its potential mechanism needs to be further studied in future. (4). The modified PEEK, including excellent osseointegration and a durable and broad-spectrum antibacterial activity, could be applied clinically to address PJI which is a hot potato for surgeons and patients undergoing total joint arthroplasty.

Nano Textured PEEK Surface for Enhanced Osseointegration.

Polyetheretherketone (PEEK) is widely used in orthopedic and dental applications because of its similar mechanical properties to those of natural bones. However, the inferior osseointegration and bioinertness hamper the clinic application. The surface texture of biomaterials plays an essential role in controlling cell differentiation through affecting the cell-generated physical forces, thus improving the osseointegration of the substrate. In this work, argon PIII and subsequently hydrogen peroxide treatment are applied to construct the nanostructure on the PEEK surface. The in vitro results show that the cell adhesion, collagen secretion, and extracellular matrix (ECM) deposition can be enhanced on both nanostructured surfaces. The in vivo tests exhibit that the surface fabricated by physical-chemical treatment is more favorable for fibrous tissue filtration inhibition and osseointegration than that fabricated by argon PIII only. This work provides a candidate approach for improving the osseointegration ability of PEEK implant by constructing the nanostructure on its surface, which paves the way of applying PEEK in orthopedic and dental applications.

Controllable and durable release of BMP-2-loaded 3D porous sulfonated polyetheretherketone (PEEK) for osteogenic activity enhancement.

Polyetheretherketone (PEEK) is ideal for dental and orthopedic applications because its mechanical properties are similar to cortical bones. However, its inherent inert ability hinders its clinical applications. In this work, bone morphogenetic protein-2 (BMP-2) was immobilized onto the sulfonated PEEK (SPEEK) using lyophilization technology. The surface morphologies of the samples were analyzed by field-emission scanning electron microscopy (FE-SEM), and the chemical compositions were analyzed by energy-dispersive X-ray spectrometry (EDS). The release content of BMP-2 of the samples immersed in the PBS (pH = 7.4) was detected by a human BMP-2 ELISA kit. The results indicated that controllable and durable BMP-2 release was accomplished due to the three-dimensional (3D) network of sulfonated PEEK. The in vitro cellular experiments showed that the BMP-2-immobilized samples significantly enhanced the initial adhesion and spreading of rat bone mesenchymal stem cells (rBMSCs). Moreover, the collagen secretion, extracellular matrix mineralization and ALP activity were also improved. Thus, the BMP-2-immobilized samples greatly promoted the osteogenic differentiation of rBMSCs, which revealed that BMP-2 immobilization paves the way for the use of PEEK in clinical applications.