Drug administration via hollow microneedles (HMN) have the advantages of painlessness, avoidance of first-pass effect, capability of sustained infusion, and no need for professional personnel operation. In addition, HMN can also be applied in the fields of body fluid extraction and biosensors, showing broad application prospects. However, traditional manufacturing technologies cannot meet the demand for low-cost mass production of HMN, limiting its widespread application. This paper reviews the main manufacturing technologies used for HMN in recent years, which include photolithography and etching, laser etching, sputtering and electroplating, micro-molding, three-dimensional (3D) printing and drawing lithography. It further analyzes the characteristics and limitations of existing manufacturing technologies and points out that the combination of various manufacturing technologies can improve production efficiency to a certain extent. In addition, this paper looks forward to the future trends of HMN manufacturing technology and proposes possible directions for its development. In conclusion, it is expected that this review can provide new ideas and references for follow-up research.
Printing, Three-Dimensional ; Needles ; Humans ; Drug Delivery Systems/methods* ; Equipment Design ; Microinjections/methods*

Objective:To assess the optimal timing and short-term clinical efficacy of sinus drug-eluting stent placement in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:The minimum sample size was calculated using G-power 3.1.9.7 software. From March 2021 and May 2023, a total of 114 eligible patients with CRSwNP were recruited in this study at the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University. The patients were randomly assigned to three groups: the control group, the intraoperative stent group, and the postoperative stent group. In the intraoperative stent group, drug-eluting stents were implanted during endoscopic sinus surgery (ESS), while patients in the postoperative stent group received drug-eluting stent 2 weeks after ESS, following routine debridement of the surgical cavity. Bilateral ethmoid sinus stenting was performed for both stent groups, while the control group only underwent ESS with standard postoperative cavity debridement. All subjects were followed up at 2, 4, 8, and 12 weeks postoperatively. Nasal symptom Visual Analog Scale (VAS) scores and endoscopic evaluations of the ethmoid cavity-assessing obstruction, crusting, polypoid mucosal changes, epithelialization of ethmoid cavity, need for intervention, and complications such as middle turbinate lateralization and adhesions-were collected to evaluate the treatment efficacy of three groups. Statistical analyses were performed using GraphPad Prism 9. Analysis of variance (ANOVA) was applied to analyze continuous variables among the three groups, and chi-square tests were used for categorical variables.Results:Among 114 CRSwNP patients, 21 lost follow-up patients and 7 postoperative oral corticosteroid intervention patients were excluded. Finally, 86 patients were included in the analysis, including 45 males and 41 females, aged 18-65 years. The cohort comprised 29 in the control group, 29 in the intraoperative stent group, and 28 in the postoperative stent group. Successful bilateral ethmoid sinus stent implantation was achieved in both stent groups. At 4 weeks postoperatively, compared with the control group, both stent groups showed significant improvements in nasal congestion and rhinorrhea scores ( P<0.05). At 8 weeks, the postoperative group continued to demonstrate superior outcomes in these two symptoms (both P<0.05), while the intraoperative group only showed significant improvement in nasal congestion ( P<0.05). No significant differences were observed in facial pressure, olfactory loss, or nasal dryness scores among the three groups (all P>0.05). Endoscopic evaluation revealed that both stent groups had significant improvements in ethmoid sinus obstruction scores at 4 weeks compared with the control group, with the postoperative group maintaining this advantage at 8 weeks ( P<0.05). At 2 weeks, the intraoperative stent group had higher crusting scores than other groups ( P<0.05). At 2 weeks after stent implantation, the postoperative stent group had significantly lower crusting scores than the intraoperative stent group ( P<0.001). The intraoperative group had a significantly lower incidence of ethmoid sinus edema and polypoid changes at 4 weeks compared with the control group ( P<0.05), while the postoperative group showed reduced rates of these pathological changes at 4, 8, and 12 weeks (all P<0.05). The postoperative stent group had significantly higher rates of ethmoid sinus mucosal epithelialization at 8 and 12 weeks postoperatively compared with the control group. The intraoperative stent group required fewer interventions than the control group at both 8 and 12 weeks, while the postoperative stent group maintained lower interventions rates at all follow-up points after implantation (all P<0.05). Additionally, the incidence of complications was significantly lower in both stent groups compared with the control group ( P<0.05). Overall, stent implantation at different time points showed similar efficacy, with the postoperative group demonstrating more stable outcomes and less crusting/coagulation formation compared with the intraoperative group. Conclusions:The implantation of corticosteroid sinus stents in the ethmoid sinuses effectively controls postoperative inflammation, promotes mucosal epithelialization, and reduces postoperative intervention rates. Stent implantation two weeks after surgery is feasible. Adjusting the timing of stent placement can minimize crust formation and maximize the corticosteroid effect, thereby facilitating a benign course of the surgical site.

Objective:To assess the optimal timing and short-term clinical efficacy of sinus drug-eluting stent placement in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:The minimum sample size was calculated using G-power 3.1.9.7 software. From March 2021 and May 2023, a total of 114 eligible patients with CRSwNP were recruited in this study at the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University. The patients were randomly assigned to three groups: the control group, the intraoperative stent group, and the postoperative stent group. In the intraoperative stent group, drug-eluting stents were implanted during endoscopic sinus surgery (ESS), while patients in the postoperative stent group received drug-eluting stent 2 weeks after ESS, following routine debridement of the surgical cavity. Bilateral ethmoid sinus stenting was performed for both stent groups, while the control group only underwent ESS with standard postoperative cavity debridement. All subjects were followed up at 2, 4, 8, and 12 weeks postoperatively. Nasal symptom Visual Analog Scale (VAS) scores and endoscopic evaluations of the ethmoid cavity-assessing obstruction, crusting, polypoid mucosal changes, epithelialization of ethmoid cavity, need for intervention, and complications such as middle turbinate lateralization and adhesions-were collected to evaluate the treatment efficacy of three groups. Statistical analyses were performed using GraphPad Prism 9. Analysis of variance (ANOVA) was applied to analyze continuous variables among the three groups, and chi-square tests were used for categorical variables.Results:Among 114 CRSwNP patients, 21 lost follow-up patients and 7 postoperative oral corticosteroid intervention patients were excluded. Finally, 86 patients were included in the analysis, including 45 males and 41 females, aged 18-65 years. The cohort comprised 29 in the control group, 29 in the intraoperative stent group, and 28 in the postoperative stent group. Successful bilateral ethmoid sinus stent implantation was achieved in both stent groups. At 4 weeks postoperatively, compared with the control group, both stent groups showed significant improvements in nasal congestion and rhinorrhea scores ( P<0.05). At 8 weeks, the postoperative group continued to demonstrate superior outcomes in these two symptoms (both P<0.05), while the intraoperative group only showed significant improvement in nasal congestion ( P<0.05). No significant differences were observed in facial pressure, olfactory loss, or nasal dryness scores among the three groups (all P>0.05). Endoscopic evaluation revealed that both stent groups had significant improvements in ethmoid sinus obstruction scores at 4 weeks compared with the control group, with the postoperative group maintaining this advantage at 8 weeks ( P<0.05). At 2 weeks, the intraoperative stent group had higher crusting scores than other groups ( P<0.05). At 2 weeks after stent implantation, the postoperative stent group had significantly lower crusting scores than the intraoperative stent group ( P<0.001). The intraoperative group had a significantly lower incidence of ethmoid sinus edema and polypoid changes at 4 weeks compared with the control group ( P<0.05), while the postoperative group showed reduced rates of these pathological changes at 4, 8, and 12 weeks (all P<0.05). The postoperative stent group had significantly higher rates of ethmoid sinus mucosal epithelialization at 8 and 12 weeks postoperatively compared with the control group. The intraoperative stent group required fewer interventions than the control group at both 8 and 12 weeks, while the postoperative stent group maintained lower interventions rates at all follow-up points after implantation (all P<0.05). Additionally, the incidence of complications was significantly lower in both stent groups compared with the control group ( P<0.05). Overall, stent implantation at different time points showed similar efficacy, with the postoperative group demonstrating more stable outcomes and less crusting/coagulation formation compared with the intraoperative group. Conclusions:The implantation of corticosteroid sinus stents in the ethmoid sinuses effectively controls postoperative inflammation, promotes mucosal epithelialization, and reduces postoperative intervention rates. Stent implantation two weeks after surgery is feasible. Adjusting the timing of stent placement can minimize crust formation and maximize the corticosteroid effect, thereby facilitating a benign course of the surgical site.

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.