Abstract
In this study, the electrospinning technique was employed to create a nanofiber membrane by stretching an organic polymer into nanofibers under a high electric field. Metronidazole (MNZ) at a concentration of 3 wt% was loaded into a poly(lactic-co-glycolic acid) (PLGA) and silk fibroin (SF)-blended nanofiber membrane. This formulation aims to achieve effective and sustained drug release, enabling the eradication of bacteria for the efficient treatment of periodontitis. Results demonstrated that SF interacted with PLGA molecules, forming dense and uniform nanofibers with a diameter of 570 nm. Excessive SF molecules tended to aggregate, leading to an increased particle size, with the interaction between MNZ and SF contributing to adhesion. The composition of MNZ, SF, and PLGA formed a physical chimera without any chemical reactions. Moreover, as the SF content increased, the tensile properties of the membrane gradually improved. Concurrently, the in vitro degradation rate increased with higher SF content. Among the various groups tested, the 3 wt% MNZ/PLGA/SF 2:1 membrane exhibited superior drug release characteristics, with 71.76% release within 24 h. This formulation demonstrated excellent antibacterial properties, indicated by a bacterial inhibition diameter of 13.5 mm, noteworthy hydrophilicity with a contact angle of 44.3°, and favorable biocompatibility. The membrane holds significant application value in regenerative engineering and drug delivery systems, showcasing substantial potential for the treatment of periodontitis.
1 Introduction
Periodontitis stands as a chronic inflammatory and destructive oral disease primarily characterized by the formation of plaque beneath the gingiva [1]. The pathogenesis of periodontitis involves the gradual erosion of periodontal tissue integrity by the host’s immune system and bacterial infection, potentially leading to the absorption of alveolar bone and loss of periodontal ligament attachment [2]. This progressive process results in the loosening of teeth and, ultimately, tooth loss. The primary objective of early periodontal treatment is to control inflammation and prevent the further progression of periodontitis [3]. The success of periodontal treatment crucially hinges on the judicious selection of the right antibacterial drug and the appropriate route of administration [4]. The main pathogenic bacteria of periodontitis are anaerobic bacteria, and Escherichia coli is also one of the pathogenic bacteria. Metronidazole (MNZ) emerges as a fitting antimicrobial agent for the treatment of periodontitis. With its nitro structure, it actively participates in the energy metabolism of bacteria, disrupting the structure of genetic material (DNA), and inhibiting DNA synthesis. This interference effectively disrupts the growth and reproduction of pathogenic microorganisms, thereby exerting a sterilizing effect [5]. MNZ demonstrates potent bactericidal effects against bacteria [6].
In clinical practice, oral antibiotics are typically prescribed for 3–5 days as part of systemic treatment. This approach necessitates administering a sufficiently high dosage to the pocket area to attain the required concentration [7]. However, prolonged or excessive antibiotic use can lead to adverse reactions, including nausea, loss of appetite, abdominal cramps, headache, and dizziness [8]. To optimize therapeutic outcomes while minimizing adverse effects, local administration is often preferred [9]. This involves loading antibacterial drugs onto a membrane, allowing for the gradual release of drug components into the periodontal pocket [10,11]. The key challenge is to maintain a sufficiently high concentration of antibacterial drugs in the periodontal pocket for an adequate duration to effectively treat periodontitis [12]. This controlled and sustained release strategy aims to eradicate bacteria while minimizing adverse effects on the body [13]. Poly(lactic-co-glycolic acid) (PLGA), a degradable synthetic polymer, boasts excellent biocompatibility and membrane-forming capabilities, making it a versatile material in pharmaceutical and biomedical applications [14,15]. PLGA-loaded nanofiber membranes with different substances were studied for periodontitis by electrospinning [16,17]. However, the strong hydrophobicity of PLGA is not conducive to the adhesion properties of periodontal barrier membranes. Meanwhile, silk fibroin (SF), primarily extracted from silkworms, is a natural polymer known for its biocompatibility, biodegradability, morphological flexibility, mechanical properties, low inflammatory response, and non-toxicity [18,19]. Therefore, synthetic polymers incorporated with natural polymers may not only enhance hydrophilicity [20] but also have better biocompatibility and could improve the cell affinity [21].
In this study, a biomembrane drug delivery system for treating periodontitis was designed, consisting of a PLGA/SF nanofiber membrane loaded with MNZ via electrospinning. Electrospinning is a versatile technique that enables the production of nanofibers with unique properties [22]. The polymer solution is sprayed and ejected in a strong electric field, where the droplets at the tip of the needle transform from a spherical shape to a conical shape. Eventually, a nanofiber film is collected on a metal collector [23]. The membrane’s forming properties, hydrophilicity, and mechanical characteristics were tailored by adjusting the PLGA and SF ratio. This nanofiber membrane serves a dual purpose: controlling the drug release and facilitating absorption by surrounding tissues, ensuring a continuous release of MNZ to effectively combat bacteria and achieve the desired therapeutic effect in treating periodontitis.
2 Materials and methods
2.1 Materials
PLGA, with an analytical grade and a molecular weight of 100,000–120,000 Da, sourced from Daigang Bioengineering Co., Ltd., Jinan, Shandong, China; SF obtained from Sichuan Antibiotics Research Institute; MNZ also sourced from Sichuan Antibiotics Research Institute; hexafluoroisopropanol (HFIP) with a purity of 99.5% obtained from Adamas; osteoblasts (MC3T3-E1) acquired from the Chinese Academy of Sciences Cell Bank; and phosphate-buffered saline obtained from Feijing Biotechnology Co., Ltd.
2.2 Preparation of nanofiber membrane
PLGA was dissolved in HFIP at 15 wt% and ultrasonic for 1 h to obtain a clear yellow solution. The solution mixed with MNZ (3 wt%), and different ratio of SF (2:1 and 1:1), and pure PLGA solution as control, respectively [24]. Four milliliters of different solutions was put into a 10 ml syringe and fixed to the pusher of the electrospinning machine. A clip was attached to the needle of the syringe. The distance between the needle and the receiving roller was 20 cm, the voltage was 15 kV, the feed rate was 0.0025 mm/s, and the ambient temperature was 25°C. Pure PLGA membrane, 3 wt% MNZ/PLGA membrane, PLGA/SF 2:1 membrane, PLGA/SF 1:1 membrane, 3 wt% MNZ/PLGA/SF 2:1 membrane, and 3 wt% MNZ/PLGA/SF 1:1 membrane were fabricated and dried in a freeze dryer for 24 h and stored at 4°C.
2.3 Surface morphology
A 1 cm × 1 cm sample underwent gold sputtering for 50 s to enhance conductivity. The surface morphology, uniformity, and structure of the nanofibers were examined using scanning electron microscopy (SEM) at an acceleration voltage of 20 kV under vacuum conditions (HITACHI SU8010, Japan). To determine the average diameter, 20 randomly selected fibers were measured from SEM images, and ImageJ software was utilized for the analysis.
2.4 Contact angle
The contact angle of the nanofiber composite membrane was determined using a contact angle meter (LSA60, Germany). Three distinct points were measured for each sample. Following exposure to room temperature for 10 s, the water droplet’s image on the sample surface was captured by a camera and subsequently analyzed using the software provided by the manufacturer.
2.5 Fourier transform infrared (FTIR) spectroscopy
The functional groups of the nanofiber composite membrane were detected in the range of 400–3,500 cm−1 using an FTIR spectrophotometer (Tensor ll, Germany).
2.6 Mechanical properties
The prepared membrane was trimmed to dimensions of 5 cm in length and 1 cm in width, with a measured thickness of 0.04 mm using a screw micrometer. Tensile strength testing was conducted on a tensile strength testing machine (APLY-103, Huitai Machinery Co., Ltd., Dongguan, China) at a stretching speed of 10 mm/min. Each sample group underwent three stretching trials, and the average value was computed to determine the tensile strength.
2.7 Thermogravimetric analysis (TGA)
A 5 mg sample was introduced into an alumina crucible and subjected to testing in a nitrogen atmosphere with a heating rate of 10°C/min within the temperature range of 25–100°C. The thermal stability of the sample was assessed through TGA, and the thermogravimetric curve of the nanofiber composite membrane, spanning from room temperature to 600°C, was recorded. Differential treatment of the thermogravimetric curve was then conducted to identify the temperature range associated with rapid decomposition from the curve.
2.8 Water absorption
A 10 mg (M 0) sample was immersed in phosphate buffer for 1, 3, 6, and 24 h, respectively, at 37°C in a water bath. The samples were labeled and taken out at the specified time. The composite membrane surface was carefully dried with filter paper and weighed (M 1). The experiment was repeated three times. The water absorption of the nanofiber composite membrane was calculated by the following equation:
2.9 In vitro degradation testing
A 10 mg sample was immersed in phosphate buffer for 1, 3, 5, 7, 14, and 21 days, respectively, at 37°C in a water bath. The samples were labeled and taken out at the specified time. The samples were dried and weighed. The experiment was repeated three times.
2.10 Cytocompatibility
Osteoblast cells (MC3T3-E1) were seeded in 96-well plates at a density of 2 × 103 cells per well and cultured. Each sample occupied a 1 cm × 1 cm area. Following the manufacturer’s instructions, cell viability was assessed using a cell counting Kit-8 (CCK-8) kit at 1 and 3 days of culture. At the end of each time point, the cell culture medium was replaced. After incubating the cells with fresh culture medium containing CCK-8 reagent (1:10) at 37°C for 1 h, absorbance was measured at a wavelength of 450 nm using spectrophotometry and an enzyme-linked immunosorbent assay microwell plate reader (Epoch2, BIO-TEK, USA).
2.11 Encapsulation efficiency
The drug-loaded nanofiber membrane (10 mg) was completely dissolved in 1 ml HFIP, and methanol was added to achieve a volume of 10 ml. The mixture was sonicated for 2 h, the supernatant was separated by centrifugation, and the characteristic peak value of MNZ was obtained at 320 nm by ultraviolet spectrophotometer. The encapsulation efficiency of drug-loaded nanofiber membrane was calculated by the following formula:
2.12 Drug release
A 10 mg sample of the loaded membrane was weighed using an electronic balance. The dried loaded membrane was introduced into a beaker containing 15 ml of phosphate buffer solution. The beaker’s opening was sealed with plastic wrap, and it was positioned in a constant-temperature magnetic stirring water bath. A magnet was included to facilitate solution stirring, and the parameters were set to 37°C for 24 h. One milliliter of the solution was taken at 1, 3, 6, and 24 h, and 1 ml of phosphate buffer was immediately added to the beaker to adjust the pH to 7.2–7.4. The extracted 1 ml solution was placed in a cuvette, and absorbance was measured at a wavelength of 320 nm using a UV spectrophotometer. Corresponding absorbance values were obtained for known concentrations, and a standard curve was generated. The percentage of drug released was then calculated based on the initial weight of the drug in the drug-carrying membrane.
2.13 Antibacterial test
In the antibacterial assay, disposable inoculation rings, coated rods, and glass tubes were sterilized using UV irradiation. Bacteria were extracted using an inoculation ring, dissolved in deionized water in a glass test tube, mixed evenly, and then placed in the medium. E. coli, a Gram-negative and facultative anaerobic bacteria, is also one of the pathogenic bacteria of periodontitis. The medium’s surface was evenly coated with a coating rod. Three zones were created on the medium’s surface, and samples with a diameter of 8 mm, including PLGA, PLGA/SF 2:1, and 3 wt% MNZ/PLGA/SF 2:1, were placed on these zones. The medium was subsequently incubated in a bacterial incubator for 24 h. Antibacterial activity was evaluated by measuring the area of the antibacterial zone.
3 Results and discussion
3.1 Surface morphology
The surface morphology of the membranes is detailed in Figure 1, where distinctive features of pure PLGA, 3 wt% MNZ/PLGA, two variants of PLGA/SF, and two types of PLGA/SF-loaded membranes with 3 wt% MNZ are revealed. The pure PLGA membrane exhibits uniform size and good dispersion, with an average diameter of 310 nm. However, in the case of 3 wt% MNZ/PLGA, the diameter size increases to 420 nm. The elevated MNZ content in the spinning solution enhances solution viscosity, leading to increased fiber diameter and the occurrence of adhesion. High-viscosity solutions hinder the stretching of the polymer jet, causing enlarged droplet diameters at the needle tip, resulting in the formation of beaded fibers. SF, a high molecular weight fibrous protein, is blended with PLGA and interacts with PLGA molecules. The interaction prompts protein molecules to transition from a swollen to a compact state, wrapping internal hydrophilic groups and exposing hydrophobic groups [25]. This results in the formation of dense and uniform nanofibers. In PLGA/SF 1:1, the average diameter increases to 730 nm, showcasing significantly larger fiber diameters and the appearance of partial aggregates [26]. Excessive SF molecules can adhere to each other, forming aggregates with increased size. The average diameter of 3 wt% MNZ/PLGA/SF 2:1 is 640 nm, while that of 3 wt% MNZ/PLGA/SF 1:1 is 930 nm. The interaction between MNZ and SF contributes to adhesion. MNZ is attached to the nanofibers in the form of solid particles. The appropriate concentration of MNZ has good porosity, and the overall structure is an interpenetrating network, which provides enough space for cell nutrient exchange and drug release.

Electron microscopic observation, particle size, and contact angle of nanofibrous membranes with different compositions: (a) PLGA; (b) PLGA/SF 2:1; (c) PLGA/SF 1:1; (d) 3 wt% MNZ/PLGA; (e) 3 wt% MNZ/PLGA/SF 2:1; and (f) 3 wt% MNZ/PLGA/SF 1:1.
3.2 Contact angle
The contact angles of pure PLGA, 3 wt% MNZ/PLGA, two groups of PLGA/SF with different ratios, and two groups of PLGA/SF-loaded membranes with 3 wt% MNZ are shown in Figure 1. The wettability of the material surface can be judged by the contact angle [27]. The contact angle of pure PLGA is 117.8 ± 0.2°, indicating that it is hydrophobic. As the hydrophilic SF is continuously added, the contact angle becomes smaller, and the hydrophilicity gradually increases. Through the experimental results, it can be verified that SF is a hydrophilic material. With the addition of 3 wt% MNZ, the contact angle also becomes smaller, and the hydrophilicity further increases. The contact angle of 3 wt% MNZ/PLGA/SF 1:1 reaches 29.5 ± 0.8° compared with PLGA/SF 1:1 of 56.6 ± 0.8°. Hydrophilic groups including amino acid and hydrogen bonds of SF in the fiber membranes have a great influence on the wettability of the fiber [28]. The addition of water-soluble MNZ and the special structure of SF can effectively adjust the hydrophilicity and hydrophobicity of the composite membrane. Good hydrophilic membranes facilitate cell growth and proliferation in contact with body fluids.
3.3 FTIR spectroscopy
The infrared spectra of pure PLGA, 3 wt% MNZ/PLGA, two groups of PLGA/SF, and two groups of PLGA/SF loaded membranes with 3 wt% MNZ are shown in Figure 2(a). In the spectrum of PLGA, symmetric and asymmetric C–O–C stretching peaks appear at 1,088 and 1,187 cm−1, respectively, and the C═O stretching peak appears at 1,755 cm−1 [29]. These stretching peaks are also observed in all the prepared membranes. In the spectrum of MNZ, C–N stretching peak appears at 823 cm−1, N═O stretching peak appears at 1,365 cm−1, and C═C stretching peak appears at 1,537 cm−1. In the 3 wt% MNZ/PLGA fiber membranes, the characteristic peaks of MNZ functional groups are all obvious, and no any shift. Meanwhile, no new peaks are produced, indicating that no new chemical bonds are formed. This is consistent with physical adsorption and embedding. In the spectrum of SF, phenylalanine stretching peak appears at 1,616 cm−1 [30], amide Ⅰ stretching peak appears at 1,688 cm−1, and N–H stretching peak appears at 3,282 cm−1. These stretching peaks are also observed in PLGA/SF 2:1 and PLGA/SF 1:1. With increasing SF content, the characteristic peaks of functional groups become more obvious and no new peaks are produced, indicating that no new chemical bonds are formed. In the blends of MNZ/PLGA/SF, these characteristic peaks show better composition of MNZ, PLGA, and SF, which is consistent with physical adsorption and embedding.

Characterization of nanofibrous membranes with different compositions: (a) Fourier infrared; (b) tensile testing; (c) thermogravimetric analysis (TGA); and (d) derivative thermogravimetric (DTG) analysis.
3.4 Mechanical properties
The tensile strength of pure PLGA, 3 wt% MNZ/PLGA, two groups of PLGA/SF with different ratios, and two groups of PLGA/SF loaded membranes with 3 wt% MNZ are shown in Figure 2(b). The tensile strength of the pure PLGA membrane is 4.58 MPa, and the tensile strength of 3 wt% MNZ/PLGA membranes is 3.99 MPa. The tensile strengths of PLGA/SF 2:1 and PLGA/SF 1:1 are 5.53 and 6.03 MPa, respectively. The tensile strengths of 3 wt% MNZ/PLGA/SF 2:1 and 3 wt% MNZ/PLGA/SF 1:1 are 5.12 and 5.52 MPa, respectively. From the analysis of the three groups of MNZ/PLGA-loaded membranes with different concentrations of SF, it can be seen that as the loading MNZ, the tensile strength all decreases relative to no loading MNZ. This may be due to the weakness of the clusters of MNZ in the polymer matrix, which are easily ruptured when subjected to stress, thereby reducing the strength of the loaded membrane [31]. From the analysis of the two groups of PLGA/SF with different ratios, it can be seen that SF has good mechanical properties. As the amount of SF increases, the tensile strength is significantly enhanced. The ratio of SF and MNZ can be effectively adjusted to improve the mechanical properties of the composite membrane. Good mechanical properties can ensure the stability of the nanofiber membrane and simulate the characteristics of natural extracellular matrix, which provide good conditions for the growth and proliferation of osteoblasts, and are conducive to the induction of alveolar bone regeneration.
3.5 TGA
TGA and derivative thermogravimetric analysis of pure PLGA, 3 wt% MNZ/PLGA, two groups of PLGA/SF with different ratios, and two groups of PLGA/SF-loaded membranes with 3 wt% MNZ are shown in Figure 2(c) and (d). The initial degradation temperature of PLGA thermal degradation is about 234°C, and the decomposition rate is the fastest at 316°C. The complete degradation occurs at 400°C. When MNZ is added, the degradation temperature is slightly reduced, with a reduction range of 30°C. SF is a natural polymer compound. Under high-temperature conditions, the thermal motion of organic matter molecules is intensified, and the bond energy inside the molecules is destroyed, leading to the rupture and recombination of molecules. In this process, the carbon content gradually increases and is gradually converted into carbonaceous substances [32,33]. When SF is blended with PLGA, it decomposes to a certain extent above 50°C. As the amount of SF increases, the weight loss platform from 92 to 203°C becomes more obvious. The basic trend remains unchanged after adding 3 wt% MNZ. It can be concluded this composite membrane had good thermal stability.
3.6 Water absorption
The water absorption of pure PLGA, 3 wt% MNZ/PLGA, two groups of PLGA/SF, and two groups of PLGA/SF-loaded membranes with 3 wt% MNZ are shown in Figure 3(a). With the prolong of time, the water absorption rate of each group gradually increased. When added into MNZ, 3 wt% MNZ/PLGA has water absorption of 5.12 times than PLGA of 2.04 times after 24 h. The contact angle experiment has approved that MNZ has good hydrophilicity. After adding SF, the water absorption of PLGA/SF 2:1 is 5.96, 6.97, and 7.52 times in 6, 12, and 24 h, respectively, showing significant improvement due to high-molecular weight globular protein of SF with a high content of hydrophilic groups on its branch chain [34,35]. When SF increases, the water absorption of PLGA/SF 1:1 is 6.04, 6.71, and 7.26 times in 6, 12, and 24 h, respectively. The water absorption does not increase significantly compared to PLGA/SF 2:1, which may be due to the uneven distribution of nanofiber diameter and greater viscosity of excessive SF in the electrospinning process, which affects the water absorption [36]. The molecular structure of SF contains a β-fold structure, forming a stable hydrogen bond to attract more water molecules with the polar hydroxyl and carboxyl groups in the SF, and further improving the water absorption rate. The water absorption of 3 wt% MNZ/PLGA/SF 2:1 is 6.54, 7.02, and 8.81 times in 6, 12, and 24 h, which is superior to 3 wt% MNZ/PLGA/SF 1:1 of 6.3, 7.2, and 8.17 times. MNZ is evenly dispersed on the nanofiber membrane with good porosity, which increases the area of contact with water. The synergistic effect of MNZ and SF further enhances the water absorption, but more SF aggravates the adhesion of nanofibers, reducing the pore volume and affecting the water absorption [37].

Evaluation of nanofibrous membranes with different compositions. (a) water absorption; (b) in vitro degradation; (c) biocompatibility; and (d) encapsulation efficiency.
3.7 In vitro degradation testing
The in vitro degradation of pure PLGA, 3 wt% MNZ/PLGA, and two groups of PLGA/SF loaded membranes with 3 wt% MNZ are shown in Figure 3(b). As can be seen from the figure, the weight continues to decrease with the prolongation of degradation time. The loaded composite membranes have a higher degradation rate than the pure PLGA membrane in the first 7 days, and the weight loss rate is also higher than the pure PLGA membrane after 21 days [38]. Pure PLGA was degraded by 7.45%, and 3 wt%MNZ/PLGA was degraded by 13.63%. This trend suggests that the addition of MNZ accelerates the degradation of PLGA membranes. This is because part of the MNZ is attached to the surface of the membrane during the electrospinning process. When the membrane comes into contact with the buffer solution, the drug can quickly and directly diffuse into the buffer solution, increasing the weight loss rate of the membrane [39]. At the same time, because MNZ is a hydrophilic substance, it also promotes degradation. The PLGA/SF composite membranes have a higher degradation rate than the pure PLGA membrane with a prolong time from 7 to 21 days [40]. The degradation rate of PLGA/SF 2:1 was 13.54%, and that of PLGA/SF 1:1 was 10.98%. This trend suggests that the addition of SF accelerates the degradation of PLGA membranes [41]. SF is a highly hydrophilic substance, which promotes the absorption of the membrane, and the aqueous medium penetrates into the polymer matrix, causing the polymer chain to relax, the ester bond to start to hydrolyze, the molecular weight to decrease, and gradually degrade into low molecular weight polymers. The weight loss of PLGA/SF 1:1 is similar to that of PLGA/SF 2:1, which may be because excessive SF causes serious adhesion of nanofibers, hindering in vitro degradation. The nanofibers are cohesive in structure, and the internal ester bond is not easy to break, which hinders the degradation of the material in vitro to a certain extent. The weight of 3 wt% MNZ/PLGA/SF 2:1 was reduced to 16.63% degradation, and that of 3 wt% MNZ/PLGA/SF 1:1 was 15.73% degradation. This shows that the synergistic effect of MNZ and SF greatly promotes the degradation rate.
3.8 Biocompatibility
The biocompatibility of pure PLGA, 3 wt% MNZ/PLGA, two groups of PLGA/SF, and two groups of PLGA/SF-loaded membranes with 3 wt% MNZ are shown in Figure 3(c). Biocompatibility is an effective way to evaluate the stimulation of materials to cells, and it is also the most direct manifestation of the influence of materials on cells [42,43]. Biocompatibility fully shows the toxicity of materials to cells [44]. PLGA has good biocompatibility [45], and the number of cells in 3 wt% MNZ/PLGA increased, which may be due to the promotion of cell growth by low concentrations of MNZ. The cells in 3 wt% MNZ/PLGA/SF 2:1 and 3 wt% MNZ/PLGA/SF 1:1 increased significantly. SF has a similar amino acid composition to human skin tissue and has good biocompatibility, which promotes cell growth [46]. At the same time, a good pore structure provides cell climbing.
3.9 Encapsulation efficiency
The encapsulation efficiency of 3 wt% MNZ/PLGA drug-loaded membranes, two groups of PLGA/SF drug-loaded membranes containing 3 wt% MNZ at different ratios, is shown in Figure 3(d). The encapsulation efficiency indirectly indicates the ability of the delivery drug system. It can be seen that the encapsulation efficiency exceeded 85%, which is 3 wt% MNZ/PLGA of 85.63%, 3 wt% MNZ/PLGA/SF 2:1 of 93.25%, and 3 wt% MNZ/PLGA/SF 1:1 of 95.14%, respectively. Silk fibroin is a protein polymer composed of polypeptide chains of glycine and alanine repeating units, which is beneficial to the adsorption and adhesion of drugs, and promotes the encapsulation efficiency of MNZ in nanofiber membranes.
3.10 Drug release
The drug release profiles of 3 wt% MNZ/PLGA and two groups of PLGA/SF loaded membranes with 3 wt% MNZ are presented in Figure 4. The drug release behavior of the three groups of drug-loaded membranes can be categorized into two stages: an initial rapid release followed by a subsequent slow release [47]. At 1 h, the release rates of MNZ for 3 wt% MNZ/PLGA, 3 wt% MNZ/PLGA/SF 2:1, and 3 wt% MNZ/PLGA/SF 1:1 were 34.67, 42.36, and 36.56%, respectively. After 3 h, the cumulative release rates of MNZ were 42.79, 54.59, and 42.23%, respectively. At 6 h, the cumulative release rates of MNZ were 47.67, 65.14, and 54.59%, respectively. The cumulative release rates of MNZ were 53.63, 71.76, and 64.62% at 24 h and 66.27, 81.16, and 75.62% at 120 h, respectively, as the degradation entered the sustained release stage.

Drug release curves of nanofibrous membranes with different compositions.
The initial rapid release of the drug from the nanofibers is attributed to the substantial electrokinetic force during electrospinning and the tendency of MNZ molecules to migrate toward the fiber surface. As the composite membrane enters the buffer, the burst release occurs at the contact surface between the fiber and water, causing a sharp increase in the MNZ concentration in the buffer [48]. The faster release of 3 wt% MNZ/PLGA/SF nanofiber membrane compared to 3 wt% MNZ/PLGA may be due to the hydrophilic SF dissolving in water over time, further accelerating the rapid release of the attached nanofiber membrane. The slower release of 3 wt% MNZ/PLGA/SF 1:1 compared to 3 wt% MNZ/PLGA/SF 2:1 may be because MNZ does not easily enter the buffer as the content of SF increases, causing adhesion and reducing the release rate [49]. In the sustained release stage, the drug is gradually and slowly released as the nanofiber membrane degrades, and the sustained release time can be up to 5 days. After 5 days, the drug was released continuously but slowly, which was related to the degradation of the nanofiber membrane. The degradation rate of PLGA was relatively slow, and the drug into the nanofiber membrane was also slowly and continuously released. The 3 wt% MNZ/PLGA/SF 2:1 drug-loaded membrane demonstrated superior rapid release and sustained release compared to the other two groups during drug release. After a comprehensive evaluation, the 3 wt% MNZ/PLGA/SF 2:1 drug-loaded membrane can be considered a favorable choice for periodontitis.
3.11 Antibacterial test
The antibacterial properties of pure PLGA, 3 wt% MNZ/PLGA, and 3 wt% MNZ/PLGA/SF drug-loaded membranes are depicted in Figure 5. The antibacterial diameter of pure PLGA was 0 mm, indicating that pure PLGA had no antibacterial effect. The diameter of the nanofiber membrane was 8 mm, and the antibacterial diameter of PLGA/SF 2:1 was 8.5 ± 0.3 mm, suggesting that SF had a certain antibacterial effect. SF is a natural organic polymer derived from the silk gland of silkworms, and it serves a protective and antibacterial role. The antibacterial diameter of 3 wt% MNZ/PLGA/SF 2:1 was 13.5 ± 0.5 mm, indicating the successful loading of MNZ on the nanofibers and exhibiting excellent antibacterial activity. The antibacterial mechanism of MNZ involves the reduction of the nitro group in the molecule to an amino group inside the cell, inhibiting the synthesis of pathogenic DNA, and thus playing an antibacterial role [50]. The 3 wt% MNZ/PLGA/SF 2:1 exhibited outstanding antibacterial properties, effectively inhibiting bacterial growth.

Antibacterial diameters of pure PLGA, 3 wt% MNZ/PLGA, and 3 wt% MNZ/PLGA/SF drug-loaded membranes.
4 Conclusion
The study utilized electrospinning technology to prepare MNZ/PLGA/SF nanofibers. MNZ, PLGA, and SF were physically embedded together, and each group of molecules exhibited good physicochemical properties. With the addition of MNZ, PLGA gradually changed from a hydrophobic to a hydrophilic membrane, and the hydrophilicity was enhanced with the gradual increase of SF. MNZ/PLGA/SF nanofibers demonstrated good biocompatibility and thermal stability. The results indicated that the 3 wt% MNZ/PLGA/SF 2:1 nanofibers had a better water absorption rate, in vitro degradation rate, and drug release compared to other groups and exhibited excellent antibacterial properties. The MNZ/PLGA/SF biomembrane shows significant potential and advantages in the treatment of periodontitis.
Acknowledgments
The authors are grateful to anonymous reviewers, whose comments improved the manuscript.
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Funding information: This work was supported by the Natural Science Foundation of Sichuan Province, China (2022NSFSC1469), the Project of Chengdu Municipal Health Commission (2021059), Sichuan Province Science and Technology Transformation Project (2023ZHCG0051), Tianfu Jincheng Laboratory, City of Future Medicine project (2023ZYD0166), and Chengdu City “Unveiling and Commanding” Science and Technology Project (2024-JB00-00018-GX).
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Conflict of interest: The authors state no conflict of interest.
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Data availability statement: The raw/processed data required to reproduce these findings cannot be shared at this time, as the data form part of an ongoing study.
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Articles in the same Issue
- Research Articles
- Tension buckling and postbuckling of nanocomposite laminated plates with in-plane negative Poisson’s ratio
- Polyvinylpyrrolidone-stabilised gold nanoparticle coatings inhibit blood protein adsorption
- Energy and mass transmission through hybrid nanofluid flow passing over a spinning sphere with magnetic effect and heat source/sink
- Surface treatment with nano-silica and magnesium potassium phosphate cement co-action for enhancing recycled aggregate concrete
- Numerical investigation of thermal radiation with entropy generation effects in hybrid nanofluid flow over a shrinking/stretching sheet
- Enhancing the performance of thermal energy storage by adding nano-particles with paraffin phase change materials
- Using nano-CaCO3 and ceramic tile waste to design low-carbon ultra high performance concrete
- Numerical analysis of thermophoretic particle deposition in a magneto-Marangoni convective dusty tangent hyperbolic nanofluid flow – Thermal and magnetic features
- Dual numerical solutions of Casson SA–hybrid nanofluid toward a stagnation point flow over stretching/shrinking cylinder
- Single flake homo p–n diode of MoTe2 enabled by oxygen plasma doping
- Electrostatic self-assembly effect of Fe3O4 nanoparticles on performance of carbon nanotubes in cement-based materials
- Multi-scale alignment to buried atom-scale devices using Kelvin probe force microscopy
- Antibacterial, mechanical, and dielectric properties of hydroxyapatite cordierite/zirconia porous nanocomposites for use in bone tissue engineering applications
- Time-dependent Darcy–Forchheimer flow of Casson hybrid nanofluid comprising the CNTs through a Riga plate with nonlinear thermal radiation and viscous dissipation
- Durability prediction of geopolymer mortar reinforced with nanoparticles and PVA fiber using particle swarm optimized BP neural network
- Utilization of zein nano-based system for promoting antibiofilm and anti-virulence activities of curcumin against Pseudomonas aeruginosa
- Antibacterial effect of novel dental resin composites containing rod-like zinc oxide
- An extended model to assess Jeffery–Hamel blood flow through arteries with iron-oxide (Fe2O3) nanoparticles and melting effects: Entropy optimization analysis
- Comparative study of copper nanoparticles over radially stretching sheet with water and silicone oil
- Cementitious composites modified by nanocarbon fillers with cooperation effect possessing excellent self-sensing properties
- Confinement size effect on dielectric properties, antimicrobial activity, and recycling of TiO2 quantum dots via photodegradation processes of Congo red dye and real industrial textile wastewater
- Biogenic silver nanoparticles of Moringa oleifera leaf extract: Characterization and photocatalytic application
- Novel integrated structure and function of Mg–Gd neutron shielding materials
- Impact of multiple slips on thermally radiative peristaltic transport of Sisko nanofluid with double diffusion convection, viscous dissipation, and induced magnetic field
- Magnetized water-based hybrid nanofluid flow over an exponentially stretching sheet with thermal convective and mass flux conditions: HAM solution
- A numerical investigation of the two-dimensional magnetohydrodynamic water-based hybrid nanofluid flow composed of Fe3O4 and Au nanoparticles over a heated surface
- Development and modeling of an ultra-robust TPU-MWCNT foam with high flexibility and compressibility
- Effects of nanofillers on the physical, mechanical, and tribological behavior of carbon/kenaf fiber–reinforced phenolic composites
- Polymer nanocomposite for protecting photovoltaic cells from solar ultraviolet in space
- Study on the mechanical properties and microstructure of recycled concrete reinforced with basalt fibers and nano-silica in early low-temperature environments
- Synergistic effect of carbon nanotubes and polyvinyl alcohol on the mechanical performance and microstructure of cement mortar
- CFD analysis of paraffin-based hybrid (Co–Au) and trihybrid (Co–Au–ZrO2) nanofluid flow through a porous medium
- Forced convective tangent hyperbolic nanofluid flow subject to heat source/sink and Lorentz force over a permeable wedge: Numerical exploration
- Physiochemical and electrical activities of nano copper oxides synthesised via hydrothermal method utilising natural reduction agents for solar cell application
- A homotopic analysis of the blood-based bioconvection Carreau–Yasuda hybrid nanofluid flow over a stretching sheet with convective conditions
- In situ synthesis of reduced graphene oxide/SnIn4S8 nanocomposites with enhanced photocatalytic performance for pollutant degradation
- A coarse-grained Poisson–Nernst–Planck model for polyelectrolyte-modified nanofluidic diodes
- A numerical investigation of the magnetized water-based hybrid nanofluid flow over an extending sheet with a convective condition: Active and passive controls of nanoparticles
- The LyP-1 cyclic peptide modified mesoporous polydopamine nanospheres for targeted delivery of triptolide regulate the macrophage repolarization in atherosclerosis
- Synergistic effect of hydroxyapatite-magnetite nanocomposites in magnetic hyperthermia for bone cancer treatment
- The significance of quadratic thermal radiative scrutinization of a nanofluid flow across a microchannel with thermophoretic particle deposition effects
- Ferromagnetic effect on Casson nanofluid flow and transport phenomena across a bi-directional Riga sensor device: Darcy–Forchheimer model
- Performance of carbon nanomaterials incorporated with concrete exposed to high temperature
- Multicriteria-based optimization of roller compacted concrete pavement containing crumb rubber and nano-silica
- Revisiting hydrotalcite synthesis: Efficient combined mechanochemical/coprecipitation synthesis to design advanced tunable basic catalysts
- Exploration of irreversibility process and thermal energy of a tetra hybrid radiative binary nanofluid focusing on solar implementations
- Effect of graphene oxide on the properties of ternary limestone clay cement paste
- Improved mechanical properties of graphene-modified basalt fibre–epoxy composites
- Sodium titanate nanostructured modified by green synthesis of iron oxide for highly efficient photodegradation of dye contaminants
- Green synthesis of Vitis vinifera extract-appended magnesium oxide NPs for biomedical applications
- Differential study on the thermal–physical properties of metal and its oxide nanoparticle-formed nanofluids: Molecular dynamics simulation investigation of argon-based nanofluids
- Heat convection and irreversibility of magneto-micropolar hybrid nanofluids within a porous hexagonal-shaped enclosure having heated obstacle
- Numerical simulation and optimization of biological nanocomposite system for enhanced oil recovery
- Laser ablation and chemical vapor deposition to prepare a nanostructured PPy layer on the Ti surface
- Cilostazol niosomes-loaded transdermal gels: An in vitro and in vivo anti-aggregant and skin permeation activity investigations towards preparing an efficient nanoscale formulation
- Linear and nonlinear optical studies on successfully mixed vanadium oxide and zinc oxide nanoparticles synthesized by sol–gel technique
- Analytical investigation of convective phenomena with nonlinearity characteristics in nanostratified liquid film above an inclined extended sheet
- Optimization method for low-velocity impact identification in nanocomposite using genetic algorithm
- Analyzing the 3D-MHD flow of a sodium alginate-based nanofluid flow containing alumina nanoparticles over a bi-directional extending sheet using variable porous medium and slip conditions
- A comprehensive study of laser irradiated hydrothermally synthesized 2D layered heterostructure V2O5(1−x)MoS2(x) (X = 1–5%) nanocomposites for photocatalytic application
- Computational analysis of water-based silver, copper, and alumina hybrid nanoparticles over a stretchable sheet embedded in a porous medium with thermophoretic particle deposition effects
- A deep dive into AI integration and advanced nanobiosensor technologies for enhanced bacterial infection monitoring
- Effects of normal strain on pyramidal I and II 〈c + a〉 screw dislocation mobility and structure in single-crystal magnesium
- Computational study of cross-flow in entropy-optimized nanofluids
- Significance of nanoparticle aggregation for thermal transport over magnetized sensor surface
- A green and facile synthesis route of nanosize cupric oxide at room temperature
- Effect of annealing time on bending performance and microstructure of C19400 alloy strip
- Chitosan-based Mupirocin and Alkanna tinctoria extract nanoparticles for the management of burn wound: In vitro and in vivo characterization
- Electrospinning of MNZ/PLGA/SF nanofibers for periodontitis
- Photocatalytic degradation of methylene blue by Nd-doped titanium dioxide thin films
- Shell-core-structured electrospinning film with sequential anti-inflammatory and pro-neurogenic effects for peripheral nerve repairment
- Flow and heat transfer insights into a chemically reactive micropolar Williamson ternary hybrid nanofluid with cross-diffusion theory
- One-pot fabrication of open-spherical shapes based on the decoration of copper sulfide/poly-O-amino benzenethiol on copper oxide as a promising photocathode for hydrogen generation from the natural source of Red Sea water
- A penta-hybrid approach for modeling the nanofluid flow in a spatially dependent magnetic field
- Advancing sustainable agriculture: Metal-doped urea–hydroxyapatite hybrid nanofertilizer for agro-industry
- Utilizing Ziziphus spina-christi for eco-friendly synthesis of silver nanoparticles: Antimicrobial activity and promising application in wound healing
- Plant-mediated synthesis, characterization, and evaluation of a copper oxide/silicon dioxide nanocomposite by an antimicrobial study
- Effects of PVA fibers and nano-SiO2 on rheological properties of geopolymer mortar
- Investigating silver and alumina nanoparticles’ impact on fluid behavior over porous stretching surface
- Potential pharmaceutical applications and molecular docking study for green fabricated ZnO nanoparticles mediated Raphanus sativus: In vitro and in vivo study
- Effect of temperature and nanoparticle size on the interfacial layer thickness of TiO2–water nanofluids using molecular dynamics
- Characteristics of induced magnetic field on the time-dependent MHD nanofluid flow through parallel plates
- Flexural and vibration behaviours of novel covered CFRP composite joints with an MWCNT-modified adhesive
- Experimental research on mechanically and thermally activation of nano-kaolin to improve the properties of ultra-high-performance fiber-reinforced concrete
- Analysis of variable fluid properties for three-dimensional flow of ternary hybrid nanofluid on a stretching sheet with MHD effects
- Biodegradability of corn starch films containing nanocellulose fiber and thymol
- Toxicity assessment of copper oxide nanoparticles: In vivo study
- Some measures to enhance the energy output performances of triboelectric nanogenerators
- Reinforcement of graphene nanoplatelets on water uptake and thermomechanical behaviour of epoxy adhesive subjected to water ageing conditions
- Optimization of preparation parameters and testing verification of carbon nanotube suspensions used in concrete
- Max-phase Ti3SiC2 and diverse nanoparticle reinforcements for enhancement of the mechanical, dynamic, and microstructural properties of AA5083 aluminum alloy via FSP
- Advancing drug delivery: Neural network perspectives on nanoparticle-mediated treatments for cancerous tissues
- PEG-PLGA core–shell nanoparticles for the controlled delivery of picoplatin–hydroxypropyl β-cyclodextrin inclusion complex in triple-negative breast cancer: In vitro and in vivo study
- Conduction transportation from graphene to an insulative polymer medium: A novel approach for the conductivity of nanocomposites
- Review Articles
- Developments of terahertz metasurface biosensors: A literature review
- Overview of amorphous carbon memristor device, modeling, and applications for neuromorphic computing
- Advances in the synthesis of gold nanoclusters (AuNCs) of proteins extracted from nature
- A review of ternary polymer nanocomposites containing clay and calcium carbonate and their biomedical applications
- Recent advancements in polyoxometalate-functionalized fiber materials: A review
- Special contribution of atomic force microscopy in cell death research
- A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery
- Cellular senescence and nanoparticle-based therapies: Current developments and perspectives
- Cyclodextrins-block copolymer drug delivery systems: From design and development to preclinical studies
- Micelle-based nanoparticles with stimuli-responsive properties for drug delivery
- Critical assessment of the thermal stability and degradation of chemically functionalized nanocellulose-based polymer nanocomposites
- Research progress in preparation technology of micro and nano titanium alloy powder
- Nanoformulations for lysozyme-based additives in animal feed: An alternative to fight antibiotic resistance spread
- Incorporation of organic photochromic molecules in mesoporous silica materials: Synthesis and applications
- A review on modeling of graphene and associated nanostructures reinforced concrete
- A review on strengthening mechanisms of carbon quantum dots-reinforced Cu-matrix nanocomposites
- Review on nanocellulose composites and CNFs assembled microfiber toward automotive applications
- Nanomaterial coating for layered lithium rich transition metal oxide cathode for lithium-ion battery
- Application of AgNPs in biomedicine: An overview and current trends
- Nanobiotechnology and microbial influence on cold adaptation in plants
- Hepatotoxicity of nanomaterials: From mechanism to therapeutic strategy
- Applications of micro-nanobubble and its influence on concrete properties: An in-depth review
- A comprehensive systematic literature review of ML in nanotechnology for sustainable development
- Exploiting the nanotechnological approaches for traditional Chinese medicine in childhood rhinitis: A review of future perspectives
- Twisto-photonics in two-dimensional materials: A comprehensive review
- Current advances of anticancer drugs based on solubilization technology
- Recent process of using nanoparticles in the T cell-based immunometabolic therapy
- Future prospects of gold nanoclusters in hydrogen storage systems and sustainable environmental treatment applications
- Preparation, types, and applications of one- and two-dimensional nanochannels and their transport properties for water and ions
- Microstructural, mechanical, and corrosion characteristics of Mg–Gd–x systems: A review of recent advancements
- Functionalized nanostructures and targeted delivery systems with a focus on plant-derived natural agents for COVID-19 therapy: A review and outlook
- Mapping evolution and trends of cell membrane-coated nanoparticles: A bibliometric analysis and scoping review
- Nanoparticles and their application in the diagnosis of hepatocellular carcinoma
- In situ growth of carbon nanotubes on fly ash substrates
- Structural performance of boards through nanoparticle reinforcement: An advance review
- Reinforcing mechanisms review of the graphene oxide on cement composites
- Seed regeneration aided by nanomaterials in a climate change scenario: A comprehensive review
- Surface-engineered quantum dot nanocomposites for neurodegenerative disorder remediation and avenue for neuroimaging
- Graphitic carbon nitride hybrid thin films for energy conversion: A mini-review on defect activation with different materials
- Nanoparticles and the treatment of hepatocellular carcinoma
- Special Issue on Advanced Nanomaterials and Composites for Energy Conversion and Storage - Part II
- Highly safe lithium vanadium oxide anode for fast-charging dendrite-free lithium-ion batteries
- Recent progress in nanomaterials of battery energy storage: A patent landscape analysis, technology updates, and future prospects
- Special Issue on Advanced Nanomaterials for Carbon Capture, Environment and Utilization for Energy Sustainability - Part II
- Calcium-, magnesium-, and yttrium-doped lithium nickel phosphate nanomaterials as high-performance catalysts for electrochemical water oxidation reaction
- Low alkaline vegetation concrete with silica fume and nano-fly ash composites to improve the planting properties and soil ecology
- Mesoporous silica-grafted deep eutectic solvent-based mixed matrix membranes for wastewater treatment: Synthesis and emerging pollutant removal performance
- Electrochemically prepared ultrathin two-dimensional graphitic nanosheets as cathodes for advanced Zn-based energy storage devices
- Enhanced catalytic degradation of amoxicillin by phyto-mediated synthesised ZnO NPs and ZnO-rGO hybrid nanocomposite: Assessment of antioxidant activity, adsorption, and thermodynamic analysis
- Incorporating GO in PI matrix to advance nanocomposite coating: An enhancing strategy to prevent corrosion
- Synthesis, characterization, thermal stability, and application of microporous hyper cross-linked polyphosphazenes with naphthylamine group for CO2 uptake
- Engineering in ceramic albite morphology by the addition of additives: Carbon nanotubes and graphene oxide for energy applications
- Nanoscale synergy: Optimizing energy storage with SnO2 quantum dots on ZnO hexagonal prisms for advanced supercapacitors
- Aging assessment of silicone rubber materials under corona discharge accompanied by humidity and UV radiation
- Tuning structural and electrical properties of Co-precipitated and Cu-incorporated nickel ferrite for energy applications
- Sodium alginate-supported AgSr nanoparticles for catalytic degradation of malachite green and methyl orange in aqueous medium
- An environmentally greener and reusability approach for bioenergy production using Mallotus philippensis (Kamala) seed oil feedstock via phytonanotechnology
- Micro-/nano-alumina trihydrate and -magnesium hydroxide fillers in RTV-SR composites under electrical and environmental stresses
- Mechanism exploration of ion-implanted epoxy on surface trap distribution: An approach to augment the vacuum flashover voltages
- Nanoscale engineering of semiconductor photocatalysts boosting charge separation for solar-driven H2 production: Recent advances and future perspective
- Excellent catalytic performance over reduced graphene-boosted novel nanoparticles for oxidative desulfurization of fuel oil
- Special Issue on Advances in Nanotechnology for Agriculture
- Deciphering the synergistic potential of mycogenic zinc oxide nanoparticles and bio-slurry formulation on phenology and physiology of Vigna radiata
- Nanomaterials: Cross-disciplinary applications in ornamental plants
- Special Issue on Catechol Based Nano and Microstructures
- Polydopamine films: Versatile but interface-dependent coatings
- In vitro anticancer activity of melanin-like nanoparticles for multimodal therapy of glioblastoma
- Poly-3,4-dihydroxybenzylidenhydrazine, a different analogue of polydopamine
- Chirality and self-assembly of structures derived from optically active 1,2-diaminocyclohexane and catecholamines
- Advancing resource sustainability with green photothermal materials: Insights from organic waste-derived and bioderived sources
- Bioinspired neuromelanin-like Pt(iv) polymeric nanoparticles for cancer treatment
- Special Issue on Implementing Nanotechnology for Smart Healthcare System
- Intelligent explainable optical sensing on Internet of nanorobots for disease detection
- Special Issue on Green Mono, Bi and Tri Metallic Nanoparticles for Biological and Environmental Applications
- Tracking success of interaction of green-synthesized Carbopol nanoemulgel (neomycin-decorated Ag/ZnO nanocomposite) with wound-based MDR bacteria
- Green synthesis of copper oxide nanoparticles using genus Inula and evaluation of biological therapeutics and environmental applications
- Biogenic fabrication and multifunctional therapeutic applications of silver nanoparticles synthesized from rose petal extract
- Metal oxides on the frontlines: Antimicrobial activity in plant-derived biometallic nanoparticles
- Controlling pore size during the synthesis of hydroxyapatite nanoparticles using CTAB by the sol–gel hydrothermal method and their biological activities
- Special Issue on State-of-Art Advanced Nanotechnology for Healthcare
- Applications of nanomedicine-integrated phototherapeutic agents in cancer theranostics: A comprehensive review of the current state of research
- Smart bionanomaterials for treatment and diagnosis of inflammatory bowel disease
- Beyond conventional therapy: Synthesis of multifunctional nanoparticles for rheumatoid arthritis therapy