Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study.

BACKGROUND: Previous studies from this as well as other research groups suggested that non-invasive chromosome screening (NICS) with embryo culture medium can be used to identify chromosomal ploidy and chromosomal abnormalities. We here report a series of clinical cases utilizing the technology. METHODS: A total of 45 couples underwent in vitro fertilisation during a period between February 2016 and February 2017. Karyotyping revealed normal chromosomes in both partners in 23 couples, and chromosomal rearrangements in at least one partner in 22 couples. Intracytoplasmic sperm injection (ICSI) was used for fertilization. NICS was carried out using embryo culture medium at the blastocyst stage via multiple annealing and looping-based amplification cycles, whole-genome amplification and next-generation sequencing. RESULTS: A total of 413 embryos were obtained; 170 blastocysts were subjected to NICS. The screening showed euploidy in 79 embryos, aneuploidy in 52 embryos, and mosaic ploidy for 33 embryos. The rate of euploidy was comparable in couples with normal karyotype (50.7%; 38/75) vs. chromosomal rearrangement (43.2%; 41/95). A total of 52 euploid embryos (50 oocyte retrieval cycles) were transferred in 43 women. Biochemical pregnancy rate was 72.0% (36/50). Clinical pregnancy rate was 58.0% (29/50). The rate of spontaneous miscarriage was 3/29 (none with chromosomal aneuploidy). A total of 27 healthy babies were delivered. CONCLUSIONS: NICS could identify embryo chromosomal abnormalities in couples either with or without chromosomal rearrangement, with satisfying clinical outcomes.

A candidate DNA vaccine encoding a fusion protein of porcine complement C3d-P28 and ORF2 of porcine circovirus type 2 induces cross-protective immunity against PCV2b and PCV2d in pigs.

BACKGROUND: Porcine circovirus type 2 (PCV2) is an economically important viral pathogen for swine industry worldwide. However, current PCV2 vaccines provide incomplete protection against the PCV2d, which has recently emerged as the predominant pathogenic form of PCV2. METHODS: To develop a novel DNA vaccine with high efficacy against PCV2d virus, we fused the ORF2 of PCV2d to three copies of the minimum-binding domain of the complement C3 cascade terminal component, C3d-P28. Expression of ORF2 alone (pVO) or fused C3d-P28 (pVOC3) were verified by immunofluorescent assay. Vaccine efficacy was tested by measured the DNA copy and T and B cell immune response. RESULTS: Vaccination with pVOC3 reduced the levels of PCV2 genomic DNA after pigs were infected with either PCV2b or PCV2d genotypes, produced potent antibodies against PCV2, and stimulated PCV2-specific interferon-γ secreting cells. CONCLUSION: Results suggested pVOC3 would be a safe and effective DNA vaccine to confer cross-protection against both PCV2b and PCV2d genotypes in pigs.

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization.

Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.

Altered microRNAs expression profiling in mice with diabetic neuropathic pain.

Neuropathic pain is one of the most common chronic complications of diabetes mellitus, one hallmark of which is tactile allodynia. However, the molecular mechanisms underlying tactile allodynia are not well understood. It has been demonstrated that microRNAs (miRNAs) are essential regulators of gene expression in the nervous system where they contribute to neuronal plasticity. Thus, in this study, we investigated the differentially expressed microRNAs in the lumbar spinal dorsal horn of streptozotocin (STZ)-induced diabetic neuropathic pain (DNP) mice and vehicle controls. Results from miRNA microarrays showed that 42 miRNAs were significantly altered in DNP spinal cord tissue (P<0.05, fold change: ⩾ 2) compared with control sample. Among them, 21 miRNAs were significantly up-regulated while the other 21 down-regulated. Further validation by quantitative real-time polymerase chain reaction (qRT-PCR) indicated that the 2 significant differentially expressed candidate miRNAs (miR-184-5p and miR-190a-5p) in DNP tissue showed the same changes as in the microarray analysis. The bioinformatics analysis revealed that some of the differentially expressed miRNAs after DNP were potential regulators of some inflammation associated with genes that are known to be involved in the pathogenesis of DNP. These findings suggest that aberrant expression of miRNAs may contribute to the pathogenesis of DNP and are potential targets for therapeutic interventions following DNP.

Parameters identification for photovoltaic module based on an improved artificial fish swarm algorithm.

A precise mathematical model plays a pivotal role in the simulation, evaluation, and optimization of photovoltaic (PV) power systems. Different from the traditional linear model, the model of PV module has the features of nonlinearity and multiparameters. Since conventional methods are incapable of identifying the parameters of PV module, an excellent optimization algorithm is required. Artificial fish swarm algorithm (AFSA), originally inspired by the simulation of collective behavior of real fish swarms, is proposed to fast and accurately extract the parameters of PV module. In addition to the regular operation, a mutation operator (MO) is designed to enhance the searching performance of the algorithm. The feasibility of the proposed method is demonstrated by various parameters of PV module under different environmental conditions, and the testing results are compared with other studied methods in terms of final solutions and computational time. The simulation results show that the proposed method is capable of obtaining higher parameters identification precision.

Low-Temperature Deposited Amorphous Poly(aryl ether ketone) Hierarchically Porous Scaffolds with Strontium-Doped Mineralized Coating for Bone Defect Repair.

In recent years, the demand for clinical bone grafting has increased. As a new solution for orthopedic implants, polyether ether ketone (PEEK, crystalline PAEK) has excellent comprehensive performance and is practically applied in the clinic. In this research, a noteworthy elevated scheme to enhance the performance of PEEK scaffolds is presented. The amorphous aggregated poly (aryl ether ketone) (PAEK) resin is prepared as the matrix material, which maintains high mechanical strength and can be processed through the solution. So, the tissue engineering scaffolds with multilevel pores can be printed by low-temperature deposited manufacturing (LDM) to improve biologically inert scaffolds with smooth surfaces. Also, the feature of PAEK's solution processing is profitable to uniformly add the functional components for bone repair. Ultimately, A system of orthopedic implantable PAEK material based on intermolecular interactions, surface topology, and surface modification is established. The specific steps include synthesizing PAEK that contain polar carboxyl structures, preparing bioinks and fabricating scaffolds by LDM, preparation of scaffolds with strontium-doped mineralized coatings, evaluation of their osteogenic properties in vitro and in vivo, and investigation on the effect and mechanism of scaffolds in promoting osteogenic differentiation. This work provides an upgraded system of PAEK implantable materials for clinical application.

Spermbots and Their Applications in Assisted Reproduction: Current Progress and Future Perspectives.

Sperm quality is declining dramatically during the past decades. Male infertility has been a serious health and social problem. The sperm cell driven biohybrid nanorobot opens a new era for automated and precise assisted reproduction. Therefore, it is urgent and necessary to conduct an updated review and perspective from the viewpoints of the researchers and clinicians in the field of reproductive medicine. In the present review, we first update the current classification, design, control and applications of various spermbots. Then, by a comprehensive summary of the functional features of sperm cells, the journey of sperms to the oocyte, and sperm-related dysfunctions, we provide a systematic guidance to further improve the design of spermbots. Focusing on the translation of spermbots into clinical practice, we point out that the main challenges are biocompatibility, effectiveness, and ethical issues. Considering the special requirements of assisted reproduction, we also propose the three laws for the clinical usage of spermbots: good genetics, gentle operation and no contamination. Finally, a three-step roadmap is proposed to achieve the goal of clinical translation. We believe that spermbot-based treatments can be validated and approved for in vitro clinical usage in the near future. However, multi-center and multi-disciplinary collaborations are needed to further promote the translation of spermbots into in vivo clinical applications.

Multivariate analyses on male factors and construction of a nomogram for predicting low in vitro fertilization rate.

Low fertilization rate (LFR) and total fertilization failure (TFF) are often encountered in routine in vitro fertilization (IVF) procedure. To solve this problem, multivariate analyses on the relationship between male factors and in vitro fertilization rate were performed, and a nomogram for prediction of LFR was constructed. This retrospective study contained 2011 couples who received IVF treatment from January 2017 to December 2021. Man factors and in vitro fertilization rate were collected. Among these couples, 1347 cases had in vitro fertilization rates ≥30 % (control group), and 664 cases had in vitro fertilization rates <30 % (LFR group). Univariate analyses of male factors found that between the two groups there were significant differences (p < 0.05) in sperm progressive motility (SPR), sperm concentration (SC), total sperm number, normal sperm morphology rate (NSMR), DNA fragmentation index (DFI), sperm acrosin activity (SAA) and the clinical diagnosis of primary or secondary infertility. Multivariate logistic regression analyses showed that SPR, SAA, and SC were independent risk factors for LFR. An algorithm and a correspondent nomogram for predicting high LFR risk were constructed using data from the training cohort. The LFR nomogram exhibited an excellent discrimination power and a high fitting degree in both the training cohort (AUC = 0.90, 95 % CI: 0.88-0.92), (H-L: x2 = 5.43, p = 0.71) and validation cohort (AUC = 0.89, 95 % CI:0.87-0.92), (H-L: x2 = 7.85, p = 0.45), respectively. The decision curve analysis (DCA) demonstrated a high efficiency of the LFR nomogram for clinical utility. SPR, SAA, and SC are independent risk factors for LFR. The LFR nomogram established based on these factors could be a useful tool to predict high risk of LFR, and patients with high risk of LFR can be guided to direct ICSI procedure. Clinical application of the LFR nomogram may increase the in vitro fertilization rate by facilitating the decision making in IVF service.

Strategies to improve the performance of polyetheretherketone (PEEK) as orthopedic implants: from surface modification to addition of bioactive materials.

Polyetheretherketone (PEEK), as a high-performance polymer, is widely used for bone defect repair due to its homogeneous modulus of elasticity of human bone, good biocompatibility, excellent chemical stability and projectability. However, the highly hydrophobic surface of PEEK is biologically inert, which makes it difficult for cells and proteins to attach, and is accompanied by the development of infections that ultimately lead to failure of PEEK implants. In order to further enhance the potential of PEEK as an orthopedic implant, researchers have explored modification methods such as surface modification by physical and chemical means and the addition of bioactive substances to PEEK-based materials to enhance the mechanical properties, osteogenic activity and antimicrobial properties of PEEK. However, these current modification methods still have obvious shortcomings in terms of cost, maneuverability, stability and cytotoxicity, which still need to be explored by researchers. This paper reviews some of the modification methods that have been used to improve the performance of PEEK over the last three years in anticipation of the need for researchers to design PEEK orthopedic implants that better meet clinical needs.

Detection of human herpesviruses (HHVs) in semen of human male infertile patients.

Recently we demonstrated an ectopic expression of the human herpesvirus 1 thymidine kinase (HHV1-TK) gene by functioning of an intrinsic endogenous promoter in the transgenic rat (TG-rat), suggesting that HHV1 infection in humans induces expression of the TK gene with the ectopic promoter in the testis and results in accumulation of HHV1-TK protein, triggering male infertility similar to that in the TG-rat. Hence, in this study, we started to investigate a relationship between infection of herpesvirus and human male infertility. Semen was donated by Chinese male infertile patients (153 men, aged 21-49 years) with informed consent, followed by DNA preparation and analysis by PCR and DNA sequencing. Semen volume, sperm number and density, and sperm motility were examined. DNAs of HHV1, HHV4, HHV5 and HHV6 were confirmed by PCR, electrophoresis and DNA sequencing. Finally, virus DNA was identified in 59 patients (39%). The number of carriers was 39 (25%) for HHV1, 6 (4%) for HHV4, 33 (22%) for HHV5 and 3 (2%) for HHV6, respectively. Moreover, double-infection was found in 22 out of 59 specimens (37%), most of which were double-infection of HHV1 and HHV5 (15 out of 22 carriers). Though slight severity was present in some of the carriers, the relationship between virus infection and sperm impairment was not conclusive. Accordingly, it is essential to examine whether the viral HHV1-TK gene is expressed in the testis of the infertile human HHV carrier.

[A new puncture needle with multiple holes for testicular sperm extraction].

OBJECTIVE: To evaluate a new puncture needle with multiple holes (National Invention Patent of China: ZL 2010202466554) in testicular sperm extraction for infertile males. METHODS: This study included 215 azoospermia patients, who underwent testicular sperm extraction with a new puncture needle with multiple holes (group A, n = 133), by open biopsy (group B, n = 37), or with a fine needle (group C, n = 45). RESULTS: The first-time success rate was 100% in group A, 19% in B and 100% in C. The average operation time was obviously shorter in group A ([3 +/- 1] min) than in B ([15 +/- 3] min) and C ([7 +/- 2] min). The rate of postoperative complications was 3.0% in group A, significantly lower than in B (21.6%) and C (11.1%). CONCLUSION: The new puncture needle with multiple holes, with its advantages of accuracy, high first-time success rate, minimal invasiveness and low rate of complications, deserves to be generally applied in testicular sperm extraction.

An atypical erectile dysfunction patient with infertility treated with penile prosthesis implantation and testicular epididymal sperm aspiration (TESA)-intracytoplasmic sperm injection (ICSI): A case report.

RATIONALE: Erectile dysfunction (ED) is common in middle-aged and elderly men, affecting more than 100 million males worldwide. Most ED cases can be attributed to organic and/or psychological factors. Here we report an atypical ED case with no clear manifestation fitting the diagnosis for recognized types of ED. PATIENT CONCERNS: The 35-year-old male is unable to have normal erection since puberty, and unable to complete intercourse with his wife. He had no history of trauma, surgery or psychiatric/psychological disease. The patient has a normal male karyotype. There is no significant finding in physical examination, nocturnal penile tumescence test, and ultrasound measurement of penis vascular functions. The serum levels of major hormones are all in normal ranges. DIAGNOSES: Atypical ED, psychogenic ED not excluded; infertility. INTERVENTIONS: Oral phosphodiesterase inhibitors Tadalafil (20 mg, BIW) or Sildenafil (50 mg, BIW) had no effect in this patient. Penile prosthesis implantation helped the patient to acquire normal sexual life, but did solve the ejaculation failure and infertility. Motile sperms were obtained by testicular epididymal sperm aspiration under the guidance of ultrasound, and intracytoplasmic sperm injection was performed with occytes retrieved from his wife. OUTCOMES: The patient sexual life was significantly improved after penile prosthesis implantation; the patient wife is currently in the first trimester of pregnancy as the result of in vitro fertilization. CONCLUSIONS: The no response to phosphodiesterase type 5 inhibitors (PDE5) treatment may suggest an impediment of PDE5-related pharmacological pathways or the presence of defect/injury in the neural system. This special case raises a question if some patients with persistent ED may have similar manifestations and can be treated with the same procedures.

Comparisons of the analgesic effect of different pulsed radiofrequency targets in SNI-induced neuropathic pain.

An injury of the peripheral nerve may lead to neuropathic pain, which could be treated with pulsed radiofrequency to the dorsal root ganglion (DRG) or peripheral nerve [the nerve trunk (NT) or proximal to the injury site (NI)]. However, it is not clear whether there is any difference in analgesic effect or maintenance among the three targets. PRF was applied to the ipsilateral L5 DRG, peripheral nerve (NT or NI) 5 days after spared nerve injury (SNI). Triptolide (10 µg/kg) or vehicle was intrathecally administered 5 days after SNI for 3 days. Mechanical withdrawal thresholds were tested after treatment at different time points. Furthermore, microglia and the P2X7 receptor (P2X7R) in the ipsilateral spinal cord were measured with immunofluorescence and western blotting, respectively. PRF + NI exerted a more remarkable analgesic effect than PRF + DRG and PRF + NT at the early stage, but PRF + DRG had a stronger analgesic effect than PRF + NI and PRF + NT at the end of our study. In addition, PRF + DRG showed no significant difference from intrathecal administration of triptolide. Moreover, SNI-induced microglia activation and upregulation of P2X7R in spinal dorsal horn could be markedly inhibited by PRF + DRG. The results suggest that the analgesic effect of PRF + DRG increased with time whereas the other two not and microglia and P2X7R in the ipsilateral spinal dorsal horn may be involved in the process.

Low-temperature deposition manufacturing technology: a novel 3D printing method for bone scaffolds.

The application of three-dimensional printing technology in the medical field has great potential for bone defect repair, especially personalized and biological repair. As a green manufacturing process that does not involve liquefication through heating, low-temperature deposition manufacturing (LDM) is a promising type of rapid prototyping manufacturing and has been widely used to fabricate scaffolds in bone tissue engineering. The scaffolds fabricated by LDM have a multi-scale controllable pore structure and interconnected micropores, which are beneficial for the repair of bone defects. At the same time, different types of cells or bioactive factor can be integrated into three-dimensional structural scaffolds through LDM. Herein, we introduced LDM technology and summarize its applications in bone tissue engineering. We divide the scaffolds into four categories according to the skeleton materials and discuss the performance and limitations of the scaffolds. The ideas presented in this review have prospects in the development and application of LDM scaffolds.

3D Printing and Performance Study of Porous Artificial Bone Based on HA-ZrO2-PVA Composites.

An ideal artificial bone implant should have similar mechanical properties and biocompatibility to natural bone, as well as an internal structure that facilitates stomatal penetration. In this work, 3D printing was used to fabricate and investigate artificial bone composites based on HA-ZrO2-PVA. The composites were proportionally configured using zirconia (ZrO2), hydroxyapatite (HA) and polyvinyl alcohol (PVA), where the ZrO2 played a toughening role and PVA solution served as a binder. In order to obtain the optimal 3D printing process parameters for the composites, a theoretical model of the extrusion process of the composites was first established, followed by the optimization of various parameters including the spray head internal diameter, extrusion pressure, extrusion speed, and extrusion line width. The results showed that, at the optimum parameters of a spray head diameter of 0.2 mm, extrusion pressure values ranging from 1-3 bar, a line spacing of 0.8-1.5 mm, and a spray head displacement range of 8-10 mm/s, a better structure of biological bone scaffolds could be obtained. The mechanical tests performed on the scaffolds showed that the elastic modulus of the artificial bone scaffolds reached about 174 MPa, which fulfilled the biomechanical requirements of human bone. According to scanning electron microscope observation of the scaffold sample, the porosity of the scaffold sample was close to 65%, which can well promote the growth of chondrocytes and angiogenesis. In addition, c5.18 chondrocytes were used to verify the biocompatibility of the composite materials, and the cell proliferation was increased by 100% when compared with that of the control group. The results showed that the composite has good biocompatibility.

Genetic variants in microRNA biogenesis pathway genes are associated with semen quality in a Han-Chinese population.

MicroRNA biogenesis genes have been confirmed involved in lots of diseases. This study evaluated the role of genetic variants in microRNA biogenesis genes in semen quality and idiopathic male infertility. Seven single-nucleotide polymorphisms (SNP) of DICER1 (rs13078, rs1057035 and rs12323635) and DROSHA (rs10719, rs2291109, rs17409893 and rs642321) were determined by TaqMan probes and SNPstream in 667 eligible infertile men and 419 fertile controls. Semen quality analysis was performed by computer-assisted sperm analysis. It was found that genetic variants of rs12323635 was associated with idiopathic male infertility. Additionally, in strategy analysis, the rs12323635 C allele might decrease the risk of oligozoospermia (OR 0.42, 95% CI 0.26-0.66; P=0.0002). The rs642321 TT genotype may have a higher risk of oligozoospermia (OR 2.38, 95% CI 1.34-4.25; P=0.003). These significant differences were retained after Bonferroni correction. The results showed that variants of DICER1 and DROSHA may modify the risk of abnormal semen parameters, which could result in male infertility. MicroRNA have been confirmed involved in lots of diseases. To our knowledge, few studies have elucidated the role of genetic variants in microRNA biogenesis genes in semen quality and idiopathic male infertility, although microRNA is indispensable in normal spermatogenesis. In this original study, we evaluated the potential impact of the polymorphisms in microRNA biogenesis genes on the risk of abnormal semen quality based on 667 infertile patients and 419 controls, and provided the first evidence that polymorphism in rs12323635 in DICER1 may modify the risk of abnormal semen parameters, which could result in male infertility.

Accumulated HSV1-TK proteins interfere with spermatogenesis through a disruption of the integrity of Sertoli-germ cell junctions.

Transgenic rats show spermatid-specific ectopic expression of the reporter gene, herpes simplex virus type1 thymidine kinase (HSV1-TK), in the testes and have demonstrated male infertility. However, the disruption of spermatogenesis and the underlying molecular mechanisms in these transgenic animals have not been well clarified. In this study, light and electron microscopic observations were performed to characterize the morphological changes in the testes. To explore the molecular mechanisms of male infertility in the HSV1-TK transgenic rat, cDNA microarray and quantitative real-time PCR analyses were performed. The seminiferous tubules of 3-month-old transgenic rats showed morphological alterations including seminiferous epithelial sloughing, vacuolization, and degeneration of spermatogenic cells, suggesting a failure of Sertoli-germ cell interaction. Components of the epididymal lumen from transgenic rats included abnormal spermatozoa, degenerating round spermatids and abnormal elongated spermatids indicating an appearance of direct impairment of spermiogenesis. cDNA microarray and real-time PCRanalyses revealed significant changes (P<0.05) in the gene expression level in six genes, testin, versican, mamdc1, fgf7, ostf1 and cnot7. Among them, testin drew most of our attention, since the testin gene is a sensitive marker for disruption of Sertoli-germ cell adhesion. Thus, our results suggest that the accumulation of HSV1-TK in the spermatids not only directly interferes with spermiogenesis but also disrupts spermatogenesis through a disruption of Sertoli-germ cell adhesions. It is important to explore the testicular actions of the HSV1-TK protein in transgenic experimental models and thereby gain clues to find an appropriate treatment for HSV-infected patients exhibiting human male infertility, as has been recently observed.

Preparation, characterization, and phenol adsorption of activated carbons from oxytetracycline bacterial residue.

UNLABELLED: The oxytetracycline bacterial residue-activated carbon (OBR-AC) prepared from oxytetracycline bacterial residue with K2CO3 under chemical activation was studied. The effects of activation temperature, activation time, and activation ratio on the specific surface area (SSA) and methylene blue adsorption (MBA) were studied. Characterization of the optimum OBR-AC was performed by using scanning electron microscopy (SEM), pore structure (PS,) and Fourier-transform infrared spectroscopy (FT-IR). The optimum parameters were as follows: 800 degrees C activation temperature, 3 hr activation time, and 1:3 activation ratio. The SSA and MBA under optimum conditions were 1593.09 m2/g and 117.0 mg/g, respectively. Adsorption equilibrium and kinetics data were determined for the adsorption of phenol from the synthetically prepared phenol solution. The results showed that the Langmuir model gave the best fit for equilibrium isotherm, whereas the kinetics data were well fitted by the pseudo-second order model. IMPLICATIONS: In the past, the bacterial residues have been used for feed additives in China. Unfortunately, doubts of its suitability as a feedstock have been raised because of the small amount of antibiotics, a large number of the fermentation by-products and metabolic products and by-products remaining in the bacterial residues. So Oxytetracycline Bacterial Residue (OBR) is one of hazardous wastes in China. In order to solve the problem of OBR, the preparation of OBR-AC is studied, and OBR-AC under optimum operation parameters is characterized by Scanning Eldctron Microscopy (SEM), Pore Structure (PS) and Fourier Transfer-Infra Red (FT-IR). Moreover, the phenol adsorption isotherms and kinetics models for OBR-AC under optimum operation parameters are studied.

Low-Temperature Printed Hierarchically Porous Induced-Biomineralization Polyaryletherketone Scaffold for Bone Tissue Engineering.

Polyetheretherketone (PEEK) as a popular orthopaedic implant is usually fabricated into a hierarchically porous structure for improving osteogenic activity. However, the applications are limited due to the excessively high processing temperature and uncontrollably tedious modification routes. Here, an amorphous polyaryletherketone with carboxyl groups (PAEK-COOH) is synthesized and fabricated to the hierarchically controllable porous scaffolds via a low-temperature 3D-printing process. The prepared PAEK-COOH scaffolds present controllable porous structures ranging from nano- to micro-scale, and their mechanical strengths are comparable to that of trabecular bone. More importantly, the in vitro experiments show that the nanoporous surface is conducive to promoting cellular adhesion, and carboxyl groups can induce hydroxyapatite mineralization via electrostatic interaction. The in vivo experiments demonstrate that the PAEK-COOH scaffolds offer much better osseointegration without additional active ingredients, compared to that of PEEK. Therefore, this work will not only develop a promising candidate for bone tissue engineering, but provide a viable method to design PAEK biomaterials.