Engineering Bioactive M2 Macrophage-Polarized, Anti-inflammatory, miRNA-Based Liposomes for Functional Muscle Repair: From Exosomal Mechanisms to Biomaterials.

Severe inflammation and myogenic differentiation disorder are the major obstacles to skeletal muscle healing after injury. MicroRNAs (miRNAs) play an important role as regulatory molecules during the process of muscle healing, but the detailed mechanism of miRNA-mediated intercellular communication between myoblasts and macrophages remains unclear. Here, it is reported that myoblasts secrete miRNAs-enriched exosomes in the inflammatory environment, through which miR-224 is transferred into macrophages to inhibit M2 polarization. Further data demonstrate that WNT-9a may be a direct target of miR-224 for macrophage polarization. In turn, the secretome of M1 macrophages impairs myogenic differentiation and promotes proliferation. Single-cell integration analysis suggests that the elevation of exosome-derived miR-224 is caused by the activation of the key factor E2F1 in myoblasts and demonstrates the RB/E2F1/miR-224/WNT-9a axis. In vivo results show that treatment with antagomir-224 or liposomes containing miR-224 inhibitors suppresses fibrosis and improves muscle recovery. These findings indicate the importance of the crosstalk between myoblasts and macrophages via miRNA-containing exosomes in the regulation of macrophage polarization and myogenic differentiation/proliferation during muscle healing. This study provides a strategy for treating muscle injury through designing an M2 polarization-enabling anti-inflammatory and miRNA-based bioactive material.

Repair of exposure and fracture of the porous high-density polyethylene framework after ear reconstruction.

OBJECTIVE: To assess the repair method of exposure or fracture of the porous high-density polyethylene ear framework after total auricle reconstruction. STUDY DESIGN: A prospective case study. METHODS: From April 2018 to October 2021, 11 patients with framework exposure or fracture after total auricle reconstruction were admitted to the hospital for repair. In these 11 patients, the repair was performed using (1) a temporal muscle flap combined with free skin graft in 5 patients, (2) a mastoid fascia flap combined with free skin graft in 2 patients, (3) a simple local skin flap in 1 patient, (4) combination of a temporalis muscle flap and a mastoid fascia flap together with free skin graft in 2 patients, and (5) a Su-Por helix material combined with a temporal muscle flap and free skin graft in 1 patient. RESULTS: After follow-up for 3-36 months, except for one patient in whom local exposure again occurred at the same site, the framework was in a good shape in the other patients, and all the skin graft survived. CONCLUSION: The defect of the upper part of the auricle can be repaired using a temporal muscle flap combined with temporal muscle fascia and skin graft. The defect of the middle and lower part of the auricle can be repaired using a mastoid fascia flap combined with skin graft. For framework fracture, the damaged site can be first strengthened with another ear material and then combined with the adjacent fascia flap and free skin graft.

Auricular reconstruction using Medpor combined with different hearing rehabilitation approaches for microtia.

BACKGROUND: Congenital microtia-atresia affects patients in two specific ways: severe conductive hearing loss and difficulty in integrating into social environments due to auricle malformation. AIMS/OBJECTIVES: To investigate the safety and efficacy of single-stage auricular reconstruction and hearing rehabilitation in children with microtia and external auditory canal atresia. MATERIAL AND METHODS: From January 2016 to December 2019, we included 32 patients with microtia and external canal atresia who received auricle reconstruction with high-density polyethylene (Medpor) framework and three different hearing rehabilitation approaches at the Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Twenty patients underwent the traditional external auditory canal and middle ear repair (EACR), eight patients were implanted with Bonebridge (BB) devices, and four patients were implanted with bone-anchored hearing aid (BAHA) in one stage. Postoperative changes in auricle morphology and hearing and speech recognition and occurrence of complications were evaluated. RESULTS: After 6-24 months of follow-up, the auricle shape recovered well in all three groups, and the average score of 14 fine structures in the auricle was 9.43 (EACR), 10.67 (BB), and 9.75 (BAHA) points. The average score of auricle symmetry was 6.83 (EACR), 6.00 (BB), and 6.44 (BAHA) points. No significant differences in auricle shape were observed among the three groups (p > .05). After surgery, the average hearing improvement in the BB group was 43.33 dB, and the average speech recognition threshold declined to 42.28 dB. In the BAHA group, the average hearing improvement was 35 dB, and the average speech recognition threshold declined to 33.5 dB, similar to that of the BB group. However, in the EACR group, the average hearing improvement was only 4.13 dB, and the average speech recognition threshold declined to 11.36 dB. No vertigo, tinnitus, cerebrospinal fluid leakage, facial nerve paralysis, osseointegration failure, and other complications occurred in all the patients. In the EACR group, auricle stent fracture, ear canal restenosis, and canal atresia occurred in one patient each. In the BAHA group, two patients developed local ear infections. CONCLUSIONS AND SIGNIFICANCE: The procedure of single-stage auricular reconstruction and hearing rehabilitation for microtia is feasible and effective. The appropriate method of hearing reconstruction should be determined by evaluating the development of the inner and middle ear of the patients. For those patients with poor development of the mastoid and ossicular chain, hearing aid devices are recommended to achieve a stable and significant hearing effect.

Enhanced tolerance and antitumor efficacy by docetaxel-loaded albumin nanoparticles.

Docetaxel is one of the most active chemotherapeutic agents for cancer treatment. The traditional docetaxel injection (TAXOTERE®) is currently formulated in the surfactant polysorbate 80, which has been associated with severe adverse reactions. To avoid the use of polysorbate 80 as well as to reduce the systemic toxicity of docetaxel, in this study, docetaxel-loaded albumin nanoparticles were fabricated by a novel simple self-assembly method. The resulting nanoparticles showed a mean diameter size of 150 nm. After being encapsulated into nanoparticles, docetaxel displayed similar cytotoxicity to traditional injection. Since polysorbate 80 was not involved in nanoparticles, the hemolysis was completely eliminated. The maximal tolerance dose of nanoparticles was also increased, which allowed a higher dose to be safely intravenously injected and produced ideal antitumor effects. The 150 nm diameter also allowed the nanoparticles to accumulate in tumor tissue via the enhanced permeability and retention effect. The passive targeting ability further caused the higher antitumor effects of nanoparticles than that of traditional injection at the same dose (7.5 mg/kg). Therefore, docetaxel-loaded albumin nanoparticles fabricated by our strategy showed higher promise in their safety and effectiveness than the traditional docetaxel injection.

Assessment of surgical results in patients with empty nose syndrome using the 25-item Sino-Nasal Outcome Test Evaluation.

IMPORTANCE Empty nose syndrome (ENS) is an iatrogenic disorder, which severely affects the normal nasal breathing function. People affected by ENS may experience decreased productivity and lifestyle disruption. The 20-Item Sino-Nasal Outcome Test (SNOT-20) is a validated quality-of-life measurement and can be used to compare before and after intervention outcomes. OBJECTIVES To evaluate the effectiveness of the Medpor implant (Porex Surgical Inc) to improve the disease-specific quality of life in patients with ENS and to validate the 25-Item SNOT (SNOT-25) as an assessment tool in patients with ENS. DESIGN, SETTING, AND PARTICIPANTS We prospectively enrolled 24 patients from our hospital who received inferior turbinate reconstruction surgery after drug therapy failed to improve their symptoms. INTERVENTIONS All the patients underwent submucosal Medpor implant surgery to reconstruct their inferior turbinate. MAIN OUTCOMES AND MEASURES Patient assessments were based on the SNOT-25 questionnaire prior to surgery and at 3, 6, and 12 months after surgery. RESULTS The total scores of the SNOT-25 declined postoperatively, showing a significant difference at 3, 6, and 12 months after surgery compared with their initial visit (P = .045, P < .001, and P < .001, respectively). The 5 items most frequently reported by patients as important at their initial visit were "fatigue," "reduced concentration," "sadness," "dryness," and "nose is too open." The mean overall scores for these 5 important items also declined, showing statistically significant decreases compared with their initial visit (P < .05) and indicating that the items patients believed were important had improved. CONCLUSIONS AND RELEVANCE Medpor implant surgery in patients with ENS is associated with statistically significant improvements in disease-specific quality of life measures. The modified version of SNOT-20 Health Survey Scales, the SNOT-25,may be a useful measurement tool in patients with ENS.

Study of inferior turbinate reconstruction with Medpor for the treatment of empty nose syndrome.

OBJECTIVES/HYPOTHESIS: Patients with empty nose syndrome experience considerable discomfort in their daily lives and treatment is difficult for their physicians. The purpose of this study was to evaluate the outcome of an empty nose syndrome treatment via reconstruction of the inferior turbinate with porous polyethylene (Medpor). DESIGN AND METHOD: A prospective self-controlled study was conducted, and 19 patients suffering from empty nose syndrome underwent a surgical therapy through submucosal implantation of Medpor in order to reconstruct their inferior turbinate. The outcome was assessed by comparison of the preoperative and follow-up symptoms, nasal endoscopy findings, CT scans, mucociliary clearance, acoustic rhinometry, and the Sino-Nasal Outcome Test-20 scores. RESULTS: In a follow-up period of 3 to 18 months, all patients reported subjective symptom improvements and a statistically significant improvement of the Sino-Nasal Outcome Test scores was achieved (P < 0.05). Mucociliary clearance assessments showed improvements at 3, 6, and 12 months postoperatively, but without statistical significance. Acoustic rhinometry assessments showed postoperative improvements of nasal resistance, nasal volume, and minimum cross-sectional area with a significant overall average score (P < 0.05). CONCLUSION: The reconstruction of inferior turbinate with Medpor is a new promising approach to treat patients with empty nose syndrome. LEVEL OF EVIDENCE: 4.

The clinical outcomes of new hyaluronan nasal dressing: a prospective, randomized, controlled study.

BACKGROUND: Poor postoperative wound healing after endoscopic sinus surgery (ESS) remains a significant problem. This study evaluates the efficacy and safety of a new absorbable hyaluronan hydrogel. METHODS: A prospective, randomized, controlled trial was conducted. Fifty-five patients with bilateral ESS were recruited and randomized to receive absorbable hyaluronan hydrogel in one side as treated and the opposite side without absorbable hyaluronan hydrogel as control. Clinical outcome measures were assessed at postoperative 1, 2, 4, 8, and 12 weeks. RESULTS: Fifty-four patients completed the study. Overall, absorbable hyaluronan hydrogel significantly promotes the reepithelization process and reduces the presence of obstructing synechia, nonobstructing synechia, edema, crust, and mild mucopurulent drainage (all p ≤ 0.0002). At all postoperative follow-up visits, the promotion in reepithelization is statistically significant at 2, 4, and 8 weeks, and the reductions in the presence of nonobstructing synechia, edema, crust, and mild mucopurulent drainage are all statistically significant except for the presence of crust at 12 weeks and mild mucopurulent drainage at 1 and 12 weeks. Although the presence of obstructing synechia at each follow-up visit between groups does not reach statistical significance, the incidence ranges from 5.56 to 12.96% in the control group and from 0 to 3.70% in the treated group. No adverse event related to treatment was observed. CONCLUSION: In this clinical study, data analyses suggest that this new absorbable hyaluronan hydrogel, as nasal dressing/packing after ESS is safe and promotes the postoperative reepithelization process and reduces the presence of synechia, edema, crust, and mild mucopurulent drainage.