Propelling Multi-Modal Therapeutics of PEEK Implants through the Power of NO evolving Covalent Organic Frameworks (COFs).

The design and fabrication of NO-evolving core-shell nanoparticles (denoted as NC@Fe), comprised of BNN6-laden COF@Fe3 O4 nanoparticles, are reported. This innovation extends to the modification of 3D printed polyetheretherketone scaffolds with NC@Fe, establishing a pioneering approach to multi-modal bone therapy tailored to address complications such as device-associated infections and osteomyelitis. This work stands out prominently from previous research, particularly those relying on the use of antibiotics, by introducing a bone implant capable of simultaneous NO gas therapy and photothermal therapy (PPT). Under NIR laser irradiation, the Fe3 O4 NP core (photothermal conversion agent) within NC@Fe absorbs photoenergy and initiates electron transfer to the loaded NO donor (BNN6), resulting in controlled NO release. The additional heat generated through photothermal conversion further propels the NC@Fe nanoparticles, amplifying the therapeutic reach. The combined effect of NO release and PPT enhances the efficacy in eradicating bacteria over a more extensive area around the implant, presenting a distinctive solution to conventional challenges. Thorough in vitro and in vivo investigations validate the robust potential of the scaffold in infection control, osteogenesis, and angiogenesis, emphasizing the timeliness of this unique solution in managing complicated bone related infectious diseases.

Tuning the Emission of a Nonconventional Aggregation-Induced Emission Polymer via Silicon-Bridged Twisted Intramolecular Charge Transfer for Targeted Delivery and Visualized Drug Release.

The design of tunable luminescent biomaterials with large Stokes shifts is usually pursued by a twisted intramolecular charge transfer (TICT) effect with switchable emission colors in response to various external stimuli. However, such a strategy is usually realized in conjugated molecules containing benzene or its derivatives and consequently suffers from poor biocompatibility. In this work, a hyperbranched polysiloxane (HBPSi)-based non-conjugated fluorescent polymer with TICT and aggregation-induced emission (AIE) features is developed, and its luminescent properties, fluorescence mechanism, and potential applications are investigated. Initially, the non-conjugated HBPSi exhibits remarkable AIE characteristics due to the formation of through-space conjugation. With the introduction of the sulfur atom, a non-conjugated D-A type AIE material, HBPSi-Cys, that exhibits a dual-state emission with a large Stokes shift of 213 nm, is obtained. The correlation of the lower-energy emission band with solvent polarity suggests the existence of the TICT state. TICT and AIE characteristics direct different properties of HBPSi-Cys, with TICT regulating solvatochromic emission wavelengths and AIE manipulating the emission intensity with a compensation effect. Density functional theory calculations reveal that the non-conjugated D-A structure in HBPSi-Cys was formed across the silicon bridge, with auxochromic sulfhydryl groups and adjacent amide groups as acceptor units and amine and hydroxyl groups as donor units. Additionally, the AIE-active HBPSi could be utilized as a fluorescent probe for the analysis of metal ions. After grafting the AS1411 aptamer to HBPSi-Cys as the recognition motif, HBPSi-Apt possesses excellent targeted bioimaging, drug loading, pH/GSH dual-responsive drug release, and visualized drug delivery performance. This work provides a new way to design functional AIE polymers with tunable optical properties, and the synthesized HBPSi-Cys shows great potential as a smart fluorescent biomaterial.

Titanium-interlayer mediated hydroxyapatite coating on polyetheretherketone: a prospective study in patients with single-level cervical degenerative disc disease.

BACKGROUND: Currently, there are limited reports regarding investigation of the biological properties of polyetheretherketone (PEEK) coated with titanium (Ti) and hydroxyapatite (HA) in human. The objective of this study is to evaluate the in vivo response of the PEEK cages coated with Ti and HA versus uncoated PEEK cages after anterior cervical discectomy and fusion (ACDF) in patients with single-level cervical degenerative disc disease (CDDD). METHODS: Twenty-four patients with PEEK cages coated with Ti and HA (PEEK/Ti/HA group) were matched one-to-one with patients with uncoated PEEK cages (PEEK group) based on age, gender, and operative segment. All patients had been followed up for more than 2 years. Radiological assessments included intervertebral height (IH), C2-7 angle (C2-7a), segmental alignment (SA), and fusion rate. Clinical parameters included Visual Analogue Scale (VAS) and Japanese Orthopedic Association (JOA) scores. RESULTS: There was no statistical difference in SA, IH, and C2-7a between the two groups before and after surgery and all these parameters were restored postoperatively. The fusion rate of PEEK/Ti/HA group was significantly higher than PEEK group at 3-month post-operation (87.5% vs. 62.5%). At the last follow-up, the fusion rate of the both groups achieved 100%. The VAS and JOA scores were comparable between two groups and improved postoperatively. CONCLUSIONS: In patients with single-level ACDF, PEEK cage coated with Ti and HA provided a higher fusion rate than uncoated PEEK cage at 3-month post-operation, while both two cages could achieve solid osseous fusion at the last follow up. Compared with the uncoated PEEK cage, PEEK/Ti/HA cage yielded similar favorable segmental and overall cervical lordosis, IH, and clinical outcomes after the surgery.

3D-Printing Biodegradable PU/PAAM/Gel Hydrogel Scaffold with High Flexibility and Self-Adaptibility to Irregular Defects for Nonload-Bearing Bone Regeneration.

A three-dimensional (3D) printed biodegradable hydrogel scaffold with a strong self-expanding ability to conform to the contour of irregular bone defects and be closely adjacent to host tissues is reported herein. The scaffold has a triple cross-linked network structure consisting of photo-cross-linked polyacrylamide (PAAM) and polyurethane (PU) as the primary IPN network and chemical cross-linked gelatin (Gel) as the secondary network, which confers the scaffold with good mechanical properties. The addition of PU in the polymerization process of acrylamide (AAM) can improve the ultraviolet (UV) photocuring efficiency of the hydrogel and incorporate abundant hydrogen bonds between the PAAM copolymer chain and the PU chain. The results show that the hydrogel scaffold contains regular structures with smooth morphology, excellent dimensional stability, and uniform aperture. The degradation rate of the hydrogel scaffold is controllable through adjusting cross-linking agents and can be up to about 60% after degradation for 28 days. More importantly, the rapid self-inflating characteristic of the scaffold in water, that is, the volume of hydrogel scaffold can increase to about 8 times that of their own in an hour and can generate a slight compressive stress on the surrounding host tissue, thus stimulating the reconstruction and growth of new bone tissues. The in vitro experiment indicates that the scaffold is nontoxic and biocompatible. The in vivo experiment shows that the PU/PAAM/Gel chemically cross-linked scaffold displays the desirable osteogenic capability. This UV-curable 3D printed self-adaptive and degradable hydrogel scaffold holds great potential for nonload-bearing bone repair.

Titanium interlayer-mediated hydroxyapatite-coated polyetheretherketone cage in transforaminal lumbar interbody fusion surgery.

BACKGROUND: The variance in clinical responses to polyetheretherketone (PEEK) cages with titanium (Ti) and hydroxyapatite (HA) coatings (PEEK-Ti-HA cages) is still not clear. In this study, we aimed to evaluate the radiographic and clinical outcomes of patients undergoing TLIF using PEEK-Ti-HA cages with a particular focus on fusion rate. METHODS: A prospective and nonrandomized study was conducted to compare the outcomes of PEEK-Ti-HA cages (group A, n = 32) and uncoated PEEK cages (group B, n = 32). The follow up time was at least 2 years. The radiographic assessments included the regional lordosis (RL), disc height (DH), and fusion rate. The clinical indexes included the Japanese Orthopedic Association (JOA) scores and visual analog scale (VAS) scores (back and leg). RESULTS: No significant differences were found in the pre- and postoperative RL and DH between Group A and Group B. And RL and DH, even if there were any variance initially, were restored not long after surgery in both groups. Though Group A had a significantly higher fusion rate than group B at 3 months post-surgery (93.7% vs. 75.0%), the fusion rates for the two groups reached the same level (100%) when it comes to the final follow-up. Additionally, differences of VAS and JOA scores for the two groups in general approximate. CONCLUSIONS: PEEK-Ti-HA cages, in contrast with uncoated PEEK cages, produced a better fusion rate at 3 months after single-level TLIF. The fusion rates of both groups could get 100% at the final follow-up. PEEK-Ti-HA cages could achieve similar RL, DH, JOA scores and VAS scores in comparison with uncoated PEEK cages post-surgery.

Physicochemical and biological characteristics of BMP-2/IGF-1-loaded three-dimensional coaxial electrospun fibrous membranes for bone defect repair.

Coaxial electrospun fibrous membranes show favorable mechanical properties for use in guided bone regeneration (GBR). We used coaxial electrospinning technology to fabricate three-dimensional nanofiber membranes loaded with BMP-2 and IGF-1, and assessed the physicochemical and biological properties of these novel membranes in vitro. We fabricated four experimental groups of BMP-2/IGF-1/BSA-loaded membranes with different flow ratios (shell/core). Membrane characteristics were assessed by scanning and transmission electron microscopy, and laser confocal microscopy. Physicochemical and drug release properties were evaluated based on contact angle, mechanical property testing, X-ray diffraction analysis, and ELISA. The membranes were seeded with bone marrow-derived mesenchymal stem cells (BMMSCs) to estimate their biological properties based on cell viability and alkaline phosphatase (ALP) activity. The four membrane groups presented uniform diameters and core-shell structures. Acceleration of the shell solution flow rate increased the contact angle and mechanical properties of the fibrous membrane, while dual-factor addition did not impact fiber structure. Each drug-loaded membrane showed a gradually increasing release curve, with varying degrees of burst and sustained release. Compared to the other groups, the membranes with a core-shell flow ratio of 1:10 showed better drug-loading capacity and sustained release performance, higher biological properties and good barrier function. Optimal parameters were chosen based on the physical and chemical characteristics and biological properties of the membrane. Our results imply that the BMP-2/IGF-1/BSA-loaded coaxial electrospun fibrous membrane with optimum parameters is a suitable barrier membrane for GBR, and releases multiple factors promoting osteoconduction and osteoinduction.

Efficient removal of perrhenate/pertechnetate by a pyridinium-based porous polymer.

The extraction of 99TcO4- from radioactive effluents is extremely crucial for the purposes of nuclear disposal and environmental remediation. Herein, utilizing a facile and low-cost synthesis method, we report a pyridinium-based cationic polymer network, CPP-Cl, with impressive adsorption performance and ultrafast adsorption kinetics towards ReO4-. The structure featuring highly density of charged pyridinium units was synthesized, making it an effective adsorbent for capturing ReO4-. The material showed fast ReO4- adsorption kinetics reaching adsorption equilibrium within 30 s, an excellent capture capability of 1069.7 mg/g, and exceptional separation efficiency of 94.3% for removing 1000 ppm ReO4-. Furthermore, it possessed excellent reusability in multiple sorption/desorption trials and good uptake capacity within a widely ranging pH values. It is noteworthy that the extraction efficiency of CPP-Cl for ReO4- from simulated nuclear waste can be up to 94.2%. The favorable performance of the material in multiple tests revealed that CPP-Cl has tremendous potential as a high-efficiency sorbent for capturing 99TcO4-/ReO4- in complex nuclear associated environmental systems.

Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration.

Diabetic infectious microenvironment (DIME) frequently leads to a critical failure of osseointegration by virtue of its main peculiarities including typical hyperglycemia and pathogenic infection around implants. To address the plaguing issue, we devise a glucose-primed orthopedic implant composed of polyetheretherketone (PEEK), Cu-chelated metal-polyphenol network (hauberk coating) and glucose oxidase (GOx) for boosting diabetic osseointegration. Upon DIME, GOx on implants sostenuto consumes glucose to generate H2O2, and Cu liberated from hauberk coating catalyzes the H2O2 to highly germicidal •OH, which massacres pathogenic bacteria through photo-augmented chemodynamic therapy. Intriguingly, the catalytic efficiency of the coating gets greatly improved with the turnover number (TON) of 0.284 s-1. Moreover, the engineered implants exhibit satisfactory cytocompatibility and facilitate osteogenicity due to the presence of Cu and osteopromotive polydopamine coating. RNA-seq analysis reveals that the implants enable to combat infections and suppress pro-inflammatory phenotype (M1). Besides, in vivo evaluations utilizing infected diabetic rat bone defect models at week 4 and 8 authenticate that the engineered implants considerably elevate osseointegration through pathogen elimination, inflammation dampening and osteogenesis promotion. Altogether, our present study puts forward a conceptually new tactic that arms orthopedic implants with glucose-primed antibacterial and osteogenic capacities for intractable diabetic osseointegration.

Construction of a Ni(OH)2@CaTiO3 heterostructure on a Ti implant for enhanced osseointegration through NIR photoactivated bacterial inactivation and microenvironment optimization.

Desirable antibacterial and osseointegration abilities are essentially important for long-term survival of a Ti-orthopedic implant. Herein, a near-infrared light (NIR) excited antibacterial platform with excellent osseointegration composed of perovskite calcium titanate/nickel hydroxide on a Ti implant (Ni(OH)2@CaTiO3/Ti) was designed and successfully fabricated. The construction of the heterostructure efficiently separated the photogenerated electron-hole pairs to produce sufficient reactive oxygen species (ROS), which enabled the photoactivated bacterial inactivation (PBI) of Ti implants. The results showed that the surface-modified Ti implant displayed remarkable antibacterial ability with bacterial inhibition rates of 95.5% for E. coli and 93.8% for S. aureus under NIR excitation. Also, the intervention of Ni(OH)2 could create a slightly alkaline surface on the Ti implant, which synchronized with Ca-rich CaTiO3 to regulate the osteogenic microenvironment in favor of the adhesion, proliferation and differentiation of MC3T3-E1 cells as well as the up-regulation of osteogenesis-related gene expressions. The in vivo implantation experiments further confirmed that the heterostructured coating prominently accelerated the formation of new bone and promoted the osseointegration of Ti implants. Our work may provide a novel concept for improving the antibacterial and osseointegration abilities of Ti implants in orthopedic and dental applications.

Construction of hyperbranched polysiloxane-based multifunctional fluorescent prodrug for preferential cellular uptake and dual-responsive drug release.

Hyperbranched polymers hold great promise in nanomedicine for their controlled chemical structures, sizes, multiple terminal groups and enhanced stability than linear amphiphilic polymer assemblies. However, the rational design of hyperbranched polymer-based nanomedicine with low toxic materials, selective cellular uptake, controlled drug release, as well as real-time drug release tracking remains challenging. In this work, a hyperbranched multifunctional prodrug HBPSi-SS-HCPT is constructed basing on the nonconventional aggregation-induced emission (AIE) featured hyperbranched polysiloxanes (HBPSi). The HBPSi is a biocompatible AIE macromolecule devoid of conjugates, showing a high quantum yield of 17.88% and low cytotoxicity. By covalently grafting the anticancer drug, 10-hydroxycamptothecin (HCPT), to the HBPSi through 3,3'-dithiodipropionic acid, HBPSi-SS-HCPT is obtained. The HBPSis demonstrate obvious AIE features and it turned to aggregation-caused quenching (ACQ) after grafting HCPT owing to the FRET behavior between HBPSi and HCPT in HBPSi-SS-HCPT. In addition to on-demand HCPT release in response to changes in environmental pH and glutathione, a series of in vitro and in vivo studies revealed that HBPSi-SS-HCPT exhibits enhanced accumulation in tumor tissues through the enhanced permeation and retention (EPR) effect and preferential cancer cell uptake by charge reversal, thus resulting in apoptotic cell death subsequently. This newly developed multifunctional HBPSi-SS-HCPT prodrug provides a biocompatible strategy for controlled drug delivery, preferential cancer cell uptake, on-demand drug release and enhanced antitumor efficacy.

Modification of polyetheretherketone implants: From enhancing bone integration to enabling multi-modal therapeutics.

Polyetheretherketone (PEEK) is a popular thermoplastic material widely used in engineering applications due to its favorable mechanical properties and stability at high temperatures. With the first implantable grade PEEK being commercialized in 1990s, the use of PEEK has since grown exponentially in the biomedical field and has rapidly transformed a large section of the medical devices landscape. Nowadays, PEEK is a standard biomaterial used across a wide range of implant applications, however, its bioinertness remains a limitation for bone repair applications. The increasing demand for enhanced treatment efficacy/improved patient quality of life, calls for next-generation implants that can offer fast bone integration as well as other desirable therapeutic functions. As such, modification of PEEK implants has progressively shifted from offering desirable mechanical properties, enhancing bioactivity/fast osteointegration, to more recently, tackling post-surgery bacterial infection/biofilm formation, modulation of inflammation and management of bone cancers. Such progress is also accompanied by the evolution of the PEEK manufacturing technologies, to meet the ever increasing demand for more patient specific devices. However, no review has comprehensively covered the recently engaged application areas to date. This paper provides an up-to-date review on the development of PEEK-based biomedical devices in the past 10 years, with particularly focus on modifying PEEK for multi-modal therapeutics. The aim is to provide the peers with a timely update, which may guide and inspire the research and development of next generation PEEK-based healthcare products. STATEMENT OF SIGNIFICANCE: Significant progress has been made in PEEK processing and modification techniques in the past decades, which greatly contributed to its wide applications in the biomedical field. Despite the high volume of published literature on PEEK implant related research, there is a lack of review on its emerging applications in multi-modal therapeutics, which involve bone regeneration, anti-bacteria/anti-inflammation, and cancer inhibition, etc. This timely review covers the state-of-the-art in these exciting areas and provides the important guidance for next generation PEEK based biomedical device research and development.

3D-Printed Multifunctional Polyetheretherketone Bone Scaffold for Multimodal Treatment of Osteosarcoma and Osteomyelitis.

In this work, we developed the first 3D-printed polyetheretherketone (PEEK)-based bone scaffold with multi-functions targeting challenging bone diseases such as osteosarcoma and osteomyelitis. A 3D-printed PEEK/graphene nanocomposite scaffold was deposited with a drug-laden (antibiotics and/or anti-cancer drugs) hydroxyapatite coating. The graphene nanosheets within the scaffold served as effective photothermal agents that endowed the scaffold with on-demand photothermal conversion function under near-infrared laser irradiation. The bioactive hydroxyapatite coating significantly boosted the stem cell proliferation in vitro and promoted new bone growth in vivo. The presence of antibiotics and anti-cancer drugs enabled eradication of drug-resistant bacteria and ablation of osteosarcoma cancer cells, the treatment efficacy of which can be further enhanced by on-demand laser-induced heating. The promising results demonstrate the strong potential of our multi-functional scaffold in applications such as bone defect repair and multimodal treatment of osteosarcoma and osteomyelitis.

Preparation and characteristics of electrospinning PTH-Fc/PLCL/SF membranes for bioengineering applications.

Alveolar bone loss is always a big challenge for oral implant placement. Guided bone regeneration (GBR) is one of the solutions to fix this problem. Among all the factors, the barrier membrane plays a key role in this technology. At present, lack of the osteoinductivity remains the biggest weakness for clinical application. Focusing on this, we tried to fabricate an osteoinductive three-dimensional (3D) nanofiber membrane with drug releasing system by introducing parathyroid hormone (PTH)-Fc into the poly(lactic acid-co-caprolactone) PLCL/SF solution for electrospinning. The characteristics were determined by scanning electron microscopy, X-ray diffraction, contact angle measurement, and mechanical strength. According to the optimum parameters tested, we proceed to the in vitro experiments. Drug release and matrix degradation profiles of electrospinning fibers were investigated. Cell morphology was observed and cell proliferation was analyzed after bone marrow mesenchymal stem cells (BMMSCs) were seeded. The results showed favorable physical and chemical properties and good biocompatibility of these 3D nanofibers. The effect on the BMMSCs suggested the drug releasing promoted osteogenic differentiation of cells stably. This study exhibited a promising method of GBR oeteoinductive membrane fabrication. The bone reconstruction will be benefited from the osteogenic differentiation positive drug releasing system.

Conducting Polyetheretherketone Nanocomposites with an Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multimodal Therapeutic Applications.

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades because of its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue toward its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Because of the formation of an electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved 12 orders of magnitude enhancement in their electrical conductivity and thereby enabled electrophoretic deposition of a bioactive/antibacterial coating consisting of stearyltrimethylammonium chloride-modified hydroxyapatite. The coated composite implant shows significant boosting of bone marrow mesenchymal stem cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers has enabled laser-induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 °C in 150 s. The unique multifunctionality of the implant has also been demonstrated for photothermal applications such as enhancing bacterial eradication and tumor cell inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multifunctional implant in bone repair applications as well as multimodal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis.