Application and Development of Electrospun Nanofiber Scaffolds for Bone Tissue Engineering.

Nanofiber scaffolds have gained significant attention in the field of bone tissue engineering. Electrospinning, a straightforward and efficient technique for producing nanofibers, has been extensively researched. When used in bone tissue engineering scaffolds, electrospun nanofibers with suitable surface properties promote new bone tissue growth and enhance cell adhesion. Recent advancements in electrospinning technology have provided innovative approaches for scaffold fabrication in bone tissue engineering. This review comprehensively examines the utilization of electrospun nanofibers in bone tissue engineering scaffolds and evaluates the relevant literature. The review begins by presenting the fundamental principles and methodologies of electrospinning. It then discusses various materials used in the production of electrospun nanofiber scaffolds for bone tissue engineering, including natural and synthetic polymers, as well as certain inorganic materials. The challenges associated with these materials are also described. The review focuses on novel electrospinning techniques for scaffold construction in bone tissue engineering, such as multilayer nanofibers, multifluid electrospinning, and the integration of electrospinning with other methods. Recent advancements in electrospinning technology have enabled the fabrication of precisely aligned nanofiber scaffolds with nanoscale architectures. These innovative methods also facilitate the fabrication of biomimetic structures, wherein bioactive substances can be incorporated and released in a controlled manner for drug delivery purposes. Moreover, they address issues encountered with traditional electrospun nanofibers, such as mechanical characteristics and biocompatibility. Consequently, the development and implementation of novel electrospinning technologies have revolutionized scaffold fabrication for bone tissue engineering.

Recent progress of electrospun nanofibers as burning dressings.

Burns are a global public health problem, which brings great challenges to public health and the economy. Severe burns often lead to systemic infection, shock, multiple organ failure, and even death. With the increasing demand for the therapeutic effect of burn wounds, traditional dressings have been unable to meet people's needs due to their single function and many side effects. In this context, electrospinning shows a great prospect on the way to open up advanced wound dressings that promote wound repairing and prevent infection. With its large specific surface area, high porosity, and similar to natural extracellular matrix (ECM), electrospun nanofibers can load drugs and accelerate wound healing. It provides a promising solution for the treatment and management of burn wounds. This review article introduces the concept of burn and the types of electrospun nanofibers, then summarizes the polymers used in electrospun nanofiber dressings. Finally, the drugs (plant extracts, small molecule drugs and nanoparticles) loaded with electrospun burn dressings are summarized. Some promising aspects for developing commercial electrospun burn dressings are proposed.

Integrated Janus nanofibers enabled by a co-shell solvent for enhancing icariin delivery efficiency.

During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core-shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future.

Electrospun medicated gelatin/polycaprolactone Janus fibers for photothermal-chem combined therapy of liver cancer.

Liver cancer is a common cancer in the world, and core-shell nanoparticles as a commonly used combination therapy for local tumor ablation, have many shortcomings. In this study, photothermal Janus nanofibers were prepared using a electrospinning technology for tumor treatment, and the products were characterized and in vitro photothermal performance investigated. The micromorphology analysis showed that the photothermic agent CuS and electrospun fibers (loaded with CuS and anticancer drug dihydromyricetin) were successfully prepared, with diameters of 11.58 ± 0.27 µm and 1.19 ± 0.01 µm, respectively. Water contact angle and tensile test indicated that the fiber membranes has a certain hydrophilic adhesion and excellent mechanical strength. The fiber membranes has 808 nm near-infrared laser photothermal heating performance and photothermal stability, and it also has a strong response to the laser that penetrates biological tissue. In addition, in vitro cell culture and in vivo implantation study showed that the fiber membranes could kill HepG2 hepatocellular carcinoma cells combined with photothermal-chem and could be enriched in the implantation area, respectively. Hence, the Janus membranes may be a potential cancer treatment material.

Preparation and Investigation of Cellulose Acetate/Gelatin Janus Nanofiber Wound Dressings Loaded with Zinc Oxide or Curcumin for Enhanced Antimicrobial Activity.

The skin, as the largest organ, serves as a protective barrier against external stimuli. However, when the skin is injured, wound healing becomes a complex process influenced by physiological conditions, bacterial infections, and inflammation. To improve the process of wound healing, a variety of wound dressings with antibacterial qualities have been created. Electrospun nanofibers have gained significant attention in wound dressing research due to their large specific surface area and unique structure. One interesting method for creating Janus-structured nanofibers is side-by-side electrospinning. This work used side-by-side electrospinning to make cellulose acetate/gelatin Janus nanofibers. Curcumin and zinc oxide nanoparticles were added to these nanofibers. We studied Janus nanofibers' physicochemical characteristics and abilities to regulate small-molecule medication release. Janus nanofibers coated with zinc oxide nanoparticles and curcumin were also tested for antibacterial activity. The Janus nanofibers with specified physicochemical characteristics were successfully fabricated. Nanofibers released small-molecule medicines in a controlled manner. Additionally, the Janus nanofibers loaded with curcumin exhibited excellent antibacterial capabilities. This research contributes to the development of advanced wound dressings for promoting wound healing and combating bacterial infections.

Engineered shapes using electrohydrodynamic atomization for an improved drug delivery.

The shapes of micro- and nano-products have profound influences on their functional performances, which has not received sufficient attention during the past several decades. Electrohydrodynamic atomization (EHDA) techniques, mainly include electrospinning and electrospraying, are facile in manipulate their products' shapes. In this review, the shapes generated using EHDA for modifying drug release profiles are reviewed. These shapes include linear nanofibers, round micro-/nano-particles, and beads-on-a-string hybrids. They can be further divided into different kinds of sub-shapes, and can be explored for providing the desired pulsatile release, sustained release, biphasic release, delayed release, and pH-sensitive release. Additionally, the shapes resulted from the organizations of electrospun nanofibers are discussed for drug delivery, and the shapes and inner structures can be considered together for developing novel drug delivery systems. In future, the shapes and the related shape-performance relationships at nanoscale, besides the size, inner structure and the related structure-performance relationships, would further play their important roles in promoting the further developments of drug delivery field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Electrosprayed Eudragit RL100 nanoparticles with Janus polyvinylpyrrolidone patches for multiphase release of paracetamol.

Advanced nanotechniques and the corresponding complex nanostructures they produce represent some of the most powerful tools for developing novel drug delivery systems (DDSs). In this study, a side-by-side electrospraying process was developed for creating double-chamber nanoparticles in which Janus soluble polyvinylpyrrolidone (PVP) patches were added to the sides of Eudragit RL100 (RL100) particles. Both sides were loaded with the poorly water-soluble drug paracetamol (PAR). Scanning electron microscope results demonstrated that the electrosprayed nanoparticles had an integrated Janus nanostructure. Combined with observations of the working processes, the microformation mechanism for creating the Janus PVP patches was proposed. XRD, DSC, and ATR-FTIR experiments verified that the PAR drug was present in the Janus particles in an amorphous state due to its fine compatibility with the polymeric matrices. In vitro dissolution tests verified that the Janus nanoparticles were able to provide a typical biphasic drug release profile, with the PVP patches providing 43.8 ± 5.4% drug release in the first phase in a pulsatile manner. In vivo animal experiments indicated that the Janus particles, on one hand, could provide a faster therapeutic effect than the electrosprayed sustained-release RL100 nanoparticles. On the other hand, they could maintain a therapeutic blood drug concentration for a longer period. The controlled release mechanism of the drug was proposed. The protocols reported here pioneer a new process-structure-performance relationship for developing Janus-structure-based advanced nano-DDSs.

Electrospun Fenoprofen/Polycaprolactone @ Tranexamic Acid/Hydroxyapatite Nanofibers as Orthopedic Hemostasis Dressings.

Dressings with multiple functional performances (such as hemostasis, promoting regeneration, analgesia, and anti-inflammatory effects) are highly desired in orthopedic surgery. Herein, several new kinds of medicated nanofibers loaded with several active ingredients for providing multiple functions were prepared using the modified coaxial electrospinning processes. With an electrospinnable solution composed of polycaprolactone and fenoprofen as the core working fluid, several different types of unspinnable fluids (including pure solvent, nanosuspension containing tranexamic acid and hydroxyapatite, and dilute polymeric solution comprising tranexamic acid, hydroxyapatite, and polyvinylpyrrolidone) were explored to implement the modified coaxial processes for creating the multifunctional nanofibers. Their morphologies and inner structures were assessed through scanning and transmission electron microscopes, which all showed a linear format without the discerned beads or spindles and a diameter smaller than 1.0 µm, and some of them had incomplete core-shell nanostructures, represented by the symbol @. Additionally, strange details about the sheaths' topographies were observed, which included cracks, adhesions, and embedded nanoparticles. XRD and FTIR verified that the drugs tranexamic acid and fenoprofen presented in the nanofibers in an amorphous state, which resulted from the fine compatibility among the involved components. All the prepared samples were demonstrated to have a fine hydrophilic property and exhibited a lower water contact angle smaller than 40° in 300 ms. In vitro dissolution tests indicated that fenoprofen was released in a sustained manner over 6 h through a typical Fickian diffusion mechanism. Hemostatic tests verified that the intentional distribution of tranexamic acid on the shell sections was able to endow a rapid hemostatic effect within 60 s.

Quantum Light Generation Based on GaN Microring toward Fully On-Chip Source.

An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.

Electrospun multi-chamber core-shell nanofibers and their controlled release behaviors: A review.

Core-shell structure is a concentric circle structure found in nature. The rapid development of electrospinning technology provides more approaches for the production of core-shell nanofibers. The nanoscale effects and expansive specific surface area of core-shell nanofibers can facilitate the dissolution of drugs. By employing ingenious structural designs and judicious polymer selection, specialized nanofiber drug delivery systems can be prepared to achieve controlled drug release. The synergistic combination of core-shell structure and materials exhibits a strong strategy for enhancing the drug utilization efficiency and customizing the release profile of drugs. Consequently, multi-chamber core-shell nanofibers hold great promise for highly efficient disease treatment. However, little attention concentration is focused on the effect of multi-chamber core-shell nanofibers on controlled release of drugs. In this review, we introduced different fabrication techniques for multi-chamber core-shell nanostructures, including advanced electrospinning technologies and surface functionalization. Subsequently, we reviewed the different controlled drug release behaviors of multi-chamber core-shell nanofibers and their potential needs for disease treatment. The comprehensive elucidation of controlled release behaviors based on electrospun multi-chamber core-shell nanostructures could inspire the exploration of novel controlled delivery systems. Furthermore, once these fibers with customizable drug release profiles move toward industrial mass production, they will potentially promote the development of pharmacy and the treatment of various diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Enhancing diabetic wound healing: advances in electrospun scaffolds from pathogenesis to therapeutic applications.

Diabetic wounds are a significant subset of chronic wounds characterized by elevated levels of inflammatory cytokines, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS). They are also associated with impaired angiogenesis, persistent infection, and a high likelihood of hospitalization, leading to a substantial economic burden for patients. In severe cases, amputation or even mortality may occur. Diabetic foot ulcers (DFUs) are a common complication of diabetes, with up to 25% of diabetic patients being at risk of developing foot ulcers over their lifetime, and more than 70% ultimately requiring amputation. Electrospun scaffolds exhibit a structural similarity to the extracellular matrix (ECM), promoting the adhesion, growth, and migration of fibroblasts, thereby facilitating the formation of new skin tissue at the wound site. The composition and size of electrospun scaffolds can be easily adjusted, enabling controlled drug release through fiber structure modifications. The porous nature of these scaffolds facilitates gas exchange and the absorption of wound exudate. Furthermore, the fiber surface can be readily modified to impart specific functionalities, making electrospinning nanofiber scaffolds highly promising for the treatment of diabetic wounds. This article provides a concise overview of the healing process in normal wounds and the pathological mechanisms underlying diabetic wounds, including complications such as diabetic foot ulcers. It also explores the advantages of electrospinning nanofiber scaffolds in diabetic wound treatment. Additionally, it summarizes findings from various studies on the use of different types of nanofiber scaffolds for diabetic wounds and reviews methods of drug loading onto nanofiber scaffolds. These advancements broaden the horizon for effectively treating diabetic wounds.

Silver oxide decorated urchin-like microporous organic polymer composites as versatile antibacterial organic coating materials.

Microporous organic polymers (MOPs) and metal oxide hybrid composites are considered valuable coating materials because of their versatility derived from the synergistic combination of MOPs' inherent dispersibility and the distinctive properties of metal oxides. In this study, we present the synthesis of sea-urchin-like MOPs hybridised with silver oxide nanoparticles (Ag2O NPs) to fabricate antibacterial composites suitable for potential antibacterial coating applications. Ag2O NP-decorated urchin-like MOPs (Ag2O@UMOPs) were synthesised by employing a combination of two methods: a one-pot Lewis acid-base interaction-mediated self-assembly and a straightforward impregnation process. The as-prepared Ag2O@UMOPs demonstrated high antibacterial efficacy against both E. coli (G-) and S. aureus (G+). The antibacterial mechanism of Ag2O@UMOPs mainly involved the synergistic effects of accumulation of Ag2O@UMOPs, the release of Ag+ ions, and the generation of reactive oxygen species. The exceptional processability and biosafety of Ag2O@UMOPs make them ideal organic coating materials for convenient application on various substrates. These remarkable features of Ag2O@UMOPs provide an effective platform for potential antibacterial applications in biological sciences.

Construction and validation of a nomogram prediction model for postoperative incisional infection in ankle fractures.

The aim was to investigate the independent risk factors for postoperative incisional infection in ankle fractures and to establish a nomogram prediction model accordingly. Data were collected from ankle fracture patients in the Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2022. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors for postoperative incisional infection in ankle fractures and to establish the corresponding nomogram. Receiver operating characteristic curves were plotted and area under the curve was calculated, and calibration curves and decision curve analysis were plotted to evaluate the model performance. A total of 722 patients with ankle fractures were included in the study, and 76 patients developed postoperative incisional infections, with an incidence of 10.53%. After univariate and multivariate logistic regression analysis, a total of 5 variables were identified as independent risk factors for postoperative incisional infection in ankle fractures, namely, age ≥ 60 years (OR, 1.885; 95% CI, 1.156-3.045), having diabetes (OR1.625; 95% CI, 1.095-2.876), open fracture (OR, 5.564; 95% CI, 3.099-9.990), albumin < 35 g/L (OR, 2.618; 95% CI, 1.217-4.215), and operative time ≥ 2 hours (OR, 1.606; 95% CI, 1.077-3.247). The nomogram for postoperative incisional infection after ankle fracture constructed in this study has good predictive accuracy and helps orthopedic surgeons to intervene earlier in patients at high risk of postoperative incisional infection after ankle fracture.

Causal relationship between dried fruit intake and meniscal injuries: Two-sample Mendelian randomization.

To investigate the causal relationship between dried fruit intake and meniscal injuries using Mendelian randomization (MR). Data were pooled from large-scale genome wide association studies (GWAS), and genetic loci independently associated with dry fruit intake and meniscal injuries in populations of European origin were selected as instrumental variables. Three MR analyses, inverse variance weighting (IVW), weighted median (WME) and MR-Egger, were used to investigate the causal relationship between dried fruit intake and meniscal injuries. The results were tested for robustness by heterogeneity and multiplicity tests, and sensitivity analyses were performed using the "leave-one-out" method. The IVW results showed an OR (95 % CI) of 0.47 (0.28-0.78), P = .003, indicating a causal relationship between dried fruit intake and meniscus injury. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. The present study used a 2-sample MR analysis, and by analyzing and exploring the genetic data, the study showed that too little intake of dry fruits is a risk factor for meniscal injuries.

The causal relationship between ever smoked and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between ever smoked and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with ever smoked and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between ever smoked and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results of ever smoked showed an OR = 2.49, 95% CI = 1.05-5.91, P = .038, indicating that ever smoked is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. This study used two-sample MR analysis to analyze and explore the genetic data, and the results showed a higher prevalence of frozen shoulder in patients with ever smoked, suggesting that active control of ever smoked may reduce the occurrence of frozen shoulder.

The causal relationship between depression and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between depression and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with depression and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between depression and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an odds ratio (95% confidence interval) of 1.18 (0.91-1.53), P = .204, indicating that depression was not causally related to the development of frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using a two-sample MR analysis, and the results showed no causal relationship between depression and the occurrence of frozen shoulder, requiring the inclusion of a larger sample for the study.

The causal relationship between breast cancer and frozen shoulder: A two-sample Mendelian randomization.

To investigate the causal relationship between breast cancer and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with breast cancer and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median (WME) and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between breast cancer and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an OR (95% CI) of 1.02 (1.00-1.04), P = .048, indicating that breast cancer is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using two-sample MR analysis, and the results showed that the incidence of frozen shoulder was higher in breast cancer patients, suggesting that screening for frozen shoulder in breast cancer patients should be increased.

Tri-Layer Core-Shell Fibers from Coaxial Electrospinning for a Modified Release of Metronidazole.

Polymers are the backbone of drug delivery. Electrospinning has greatly enriched the strategies that have been explored for developing novel drug delivery systems using polymers during the past two decades. In this study, four different kinds of polymers, i.e., the water-soluble polymer poly (vinyl alcohol) (PVA), the insoluble polymer poly(ε-caprolactone) (PCL), the insoluble polymer Eudragit RL100 (ERL100) and the pH-sensitive polymer Eudragit S100 (ES100) were successfully converted into types of tri-layer tri-polymer core-shell fibers through bi-fluid coaxial electrospinning. During the coaxial process, the model drug metronidazole (MTD) was loaded into the shell working fluid, which was an emulsion. The micro-formation mechanism of the tri-layer core-shell fibers from the coaxial emulsion electrospinning was proposed. Scanning electron microscope and transmission electron microscope evaluations verified the linear morphology of the resultant fibers and their obvious tri-layer multiple-chamber structures. X-ray diffraction and Fourier transform infrared spectroscopy measurements demonstrated that the drug MTD presented in the fibers in an amorphous state and was compatible with the three polymeric matrices. In vitro dissolution tests verified that the three kinds of polymer could act in a synergistic manner for a prolonged sustained-release profile of MTD in the gut. The drug controlled-release mechanisms were suggested in detail. The protocols reported here pioneer a new route for creating a tri-layer core-shell structure from both aqueous and organic solvents, and a new strategy for developing advanced drug delivery systems with sophisticated drug controlled-release profiles.

A combined electrohydrodynamic atomization method for preparing nanofiber/microparticle hybrid medicines.

Bacterial prostatitis is a challenging condition to treat with traditional dosage forms. Physicians often prescribe a variety of dosage forms with different administration methods, which fail to provide an efficient and convenient mode of drug delivery. The aim of this work was to develop a new type of hybrid material incorporating both electrosprayed core-shell microparticles and electrospun nanofibers. A traditional Chinese medicine (Ningmitai, NMT) and a Western medicine (ciprofloxacin, CIP) were co-encapsulated within this material and were designed to be released in a separately controlled manner. Utilizing polyvinylpyrrolidone (PVP) as a hydrophilic filament-forming polymer and pH-sensitive Eudragit® S100 (ES100) as the particulate polymeric matrix, a combined electrohydrodynamic atomization (EHDA) method comprising coaxial electrospraying and blending electrospinning, was used to create the hybrids in a single-step and straightforward manner. A series of characterization methods were conducted to analyze both the working process and its final products. Scanning electron microscopy and transmission electron microscopy revealed that the EHDA hybrids comprised of both CIP-PVP nanofibers and NMT-ES100 core-shell microparticles. Multiple methods confirmed the rapid release of CIP and the sustained release of NMT. The antibacterial experiments indicated that the hybrids exhibited a more potent antibacterial effect against Escherichia coli dh5α and Bacillus subtilis Wb800 than either the separate nanofibers or microparticles. The amalgamation of fibrous nanomedicine and particulate micromedicine can expand the horizon of new types of medicines. The integration of electrospinning and coaxial electrospraying provides a straightforward approach to fabrication. By combining hydrophilic soluble polymers and pH-sensitive polymers in the hybrids, we can ensure the separate sequential controlled release of CIP and NMT for a potential synergistic and convenient therapy for bacterial prostatitis.