Anti-adhesive coatings are increasingly demanded in nasal stents to minimize secondary tissue damage and pain upon removal. However, conventional coatings are often limited by weak interfacial bonding, poor environmental stability, or insufficient biocompatibility. Here, we report a biocompatible anti-adhesive elastomer coating based on a chain entanglement model, in which polymer loops grafted onto the substrate serve as "molecular locks" to anchor a silicone oil-impregnated polydimethylsiloxane (PDMS) network via ultrasound-induced chain interpenetration. Free of toxic catalysts, fluorinated compounds, or intricate crosslinking systems, this "molecular lock"-anchored elastomer coating achieves superior anti-adhesive performance against common daily liquids, a range of biofluids (e.g., blood, mucus, saliva, tears), and blood scabs. It is applicable across a broad range of substrates, including metals, ceramics, and polymers, exhibiting MPa-level interfacial strength and ultralow droplet retention forces (approximate to 0.3 mu N). Notably, it remains stable under harsh environmental conditions, such as solvent immersion, tape peeling, heating, ultrasonication, and scratching. In a rabbit nasal septum hemostasis model, the stent with "molecular lock"-anchored elastomer coating effectively resisted blood adhesion and accelerated mucosal wound healing, offering a promising platform for next-generation biofriendly implantable device coatings.

ObjectiveTo design and validate a spherical nasal vestibular stent based on vestibular structural changes for treating nasal obstruction.MethodsThis study enrolled 99 patients with nasal obstruction and confirmed positive findings on anterior rhinoscopy. Pre- and post-dilation sinonasal computed tomography (CT) scans were obtained until symptoms nearly resolved. Three-dimensional (3D) reconstruction was utilized to evaluate anatomical changes, and Spearman correlation analysis was performed to assess the relationship between these changes and visual analog scale (VAS) scores for nasal obstruction. Based on 3D reconstructed models and computational fluid dynamics (CFD) parameter evaluations, a nitinol mesh stent customized to the anatomical characteristics of the nasal vestibule was designed. A single-arm clinical trial in 31 patients was subsequently evaluated the stent using NOSE scores, acoustic rhinometry, and rhinomanometry before and after placement. Adverse events were systematically recorded.Results3D reconstruction showed that changes in nasal vestibule volume before and after dilation correlated with patients’ VAS scores for nasal obstruction. In the clinical trial, the spherical nasal vestibular stent—designed using nasal vestibule volume data—significantly reduced nasal resistance (p < 0.05), increased nasal volume and valve area (p < 0.001), and lowered NOSE scores (p < 0.001). Most patients tolerated the stent well; side effects like dryness and pain were mild.ConclusionBased on 3D models from dilated nasal vestibules, this study designed a spherical stent that effectively relieves nasal obstruction with minimal risk, positioning it as a promising non-surgical intervention for clinical application.

Background/Objectives: The Eustachian tube (ET) is a physiological channel connecting the middle ear with the external atmosphere. The ET plays a role in maintaining the pressure balance of the middle ear, protecting it from pathogen invasion, and cleaning secretions. Eustachian tube dysfunction (ETD) can lead to middle ear diseases in animals. The ET morphological structure are different across species. Therefore, we aim to compare the anatomical and morphological of ET across species. Methods: The combined skull base–nasal approach was used to anatomy ET. Hematoxylin-eosin, luxol fast blue myelin and immunohistochemical Staining were used to observe the morphology of ET. Results: There were significant differences in the size and structure of ET among species: the rodents ET (mouse: 1.152 ± 0.084 mm; rat: 3.738 ± 0.04355 mm) is characterized by cartilage and obvious bubbles; while the miniature pigs ET (32.34 ± 2.157 mm) has a chondroid conical structure similar to that of humans. ET inflammation model was built by intro-tympanic injection of lipopolysaccharide (LPS). NADPH oxidase 2 (NOX2) significantly increased by 38.6% in inflamed mice, causing ET oxidative stress. The expressions of inflammatory factors interleukin-1β (IL-1β) and cyclooxygenase-2 (COX2) increased by 28.4% and 30.8%, resulting in thickening of the ET mucosa and infiltration of inflammatory cells. Conclusions: The combined skull base–nasal approach was an effective method to anatomy ET across species. The morphology of ET varied across species and NOX2 might play an important role in ET inflammation.

Meniscus is a wedge-shaped fibrocartilaginous tissue, playing important roles in maintaining joint stability and function. Meniscus injuries are difficult to heal and frequently progress into structural breakdown, which then leads to osteoarthritis. Regeneration of heterogeneous tissue engineering meniscus (TEM) continues to be a scientific and translational challenge. The morphology, tissue architecture, mechanical strength, and functional applications of the cultivated TEMs have not been able to meet clinical needs, which may due to the negligent attention on the importance of microenvironment in vitro and in vivo. Herein, we combined the 3D (three-dimensional)-printed gradient porous scaffolds, spatiotemporal partition release of growth factors, and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures, excellent biomechanical properties and anti-inflammatory and anti-oxidant effects. By observing the results of cell activity and differentiation, and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro, we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation, with a view to cultivating a high-quality of TEM from bench to bedside.

Excessive exudate secreted from diabetic wounds often results in skin overhydration, severe infections, and secondary damage upon dressing changes. However, conventional wound dressings are difficult to synchronously realize the non-maceration of wound sites and rapid exudate transport due to their random porous structure. Herein, a self-pumping Janus hydrogel with aligned channels (JHA) composed of hydrophilic poly (ethylene glycol) diacrylate (PEGDA) hydrogel layer and hydrophobic polyurethane (PU)/graphene oxide (GO)/polytetrafluoroethylene (PTFE) layer is designed to rapidly export exudate and accelerate diabetic wound healing. In the design, the ice-templating process endows the hydrophilic hydrogel layer with superior liquid transport ability and mechanical strength due to the formation of aligned channel structure. The hydrophobic layer with controlled thickness functions as an effective barrier to prevent exudate from wetting the skin surface. Experiments in diabetic rat model show that JHA can significantly promote re-epithelialization and collagen deposition, shorten the inflammation phase, and accelerate wound healing. This unique JHA dressing may have great potential for real-life usage in clinical patients.

Allergic rhinitis, as the most common type of rhinitis, has become a global health problem. At present, oral/intranasal administration of H-1-antihistamines and corticosteroids is considered to be the main therapeutic method for allergic rhinitis. However, the local bioavailability of the drug is low due to the systemic effect of drugs and nasal mucociliary clearance. More recently, a hydrogel-based intranasal delivery system (HIDS) is proposed and gradually developed as an emerging strategy for allergic rhinitis treatment by extending the residence time of drugs in a controlled manner. This review aims to highlight the advances in HIDS for allergic rhinitis treatment. The designs and therapeutic effect of the existing HIDS in the nasal microenvironment are described in detail. This review also provides a perspective on the future opportunities and developments of HIDS. Despite its nascent status, the future clinical and translational applications of HIDS can have a transformative impact on improving the treatment of chronic inflammation in the nasal cavity.

Abstract Since the meniscus is an important stabilizing structure of the knee joint and has a significant role in load‐bearing and shock absorption, so the complete structural and functional reconstructions of the teared menisci should be done not only after partial meniscectomy but also post total meniscectomy. So far, animal experiments and good clinical practice have showed that TMAT after total meniscectomy has partially solved the problem of structural and functional reconstructions after total meniscectomy. However, partial meniscectomy will also lead to accelerated knee degeneration, and its proportion is much higher than that of patients with total meniscectomy. Herein, the feasibility of PMAT after partial meniscectomy was investigated for the first time by using the 40% posterior horn meniscectomy model of the medial meniscus in Beagle dogs, and also for the first time, TMAT group and the total meniscectomy group were used as control groups. Compared with the TMAT, the transcriptomics evaluation, scanning electron microscope observation, histological regeneration and structure, biomechanical property, inflammation environment, and the knee function post PMAT were more similar to that of normal meniscus was first reported. This study provides a PMAT scheme with clinical translational value for the complete structural and functional reconstruction of the patients with partial meniscectomy and fills the gap in the field of teared meniscus therapy on the basis of quite well clinical applications of the meniscus repair and the TMAT.

Background: A novel braided nasal stent is an effective alternative to nasal packing after septoplasty that can be used to manage the mucosal flap after septoplasty and expand the nasal cavity. This study aimed to investigate the influence of design parameters on the mechanical properties of the nasal stent for optimal performance. Methods: A braided nasal stent modeling method was proposed and 27 stent models with a range of different geometric parameters were built. The compression behavior and bending behavior of these stent models were numerically analyzed using a finite element method (FEM). The orthogonal test was used as an optimization method, and the optimized design variables of the stent with improved performance were obtained based on range analysis and weight grade method. Results: The reaction force and bending stiffness of the braided stent increased with the wire diameter, braiding density, and external stent diameter, while wire diameter resulted as the most important determining parameter. The external stent diameter had the greatest influence on the elongation deformation. The influence of design parameters on von-Mises stress distribution of bent stent models was visualized. The stent model with geometrical parameters of 25 mm external diameter, 30° braiding angle, and 0.13 mm wire diameter (A3B3C3) had a greater reaction force but a considerably smaller bending stiffness, which was the optimal combination of parameters. Conclusion: Firstly, among the three design parameters of braided stent models, wire diameter resulted as the most important parameter determining the reaction force and bending stiffness. Secondly, the external stent diameter significantly influenced the elongation deformation during the compression simulation. Finally, 25 mm external diameter, 30° braiding angle, and 0.13 mm wire diameter (A3B3C3) was the optimal combination of stent parameters according to the orthogonal test results.

关节透明软骨自我修复能力有限,其再生仍然是临床医生和研究人员面临的巨大挑战.尽管多种传统临床治疗方法显示出一定的疗效,但各自均存在其局限性和不足.近些年来,基于细胞的再生医学为软骨病损提供了一种很有希望的治疗策略.间充质干细胞作为一种多能祖细胞,具有来源广泛、多向分化及自我更新等特征,除增殖及成软骨分化外,其免疫调节、抗炎作用和旁分泌效应亦是其促进软骨修复再生的重要机制.目前,间充质干细胞在多项体内外研究中显示出较好的软骨修复效果.本文就近些年来应用于软骨修复再生的间充质干细胞生物学特征、常见组织来源、实际应用情况、各自的优缺点、最终去向和转归及促软骨修复再生机制等方面的研究进展进行综述.

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.

Purpose: To examine the indications and outcomes of medial patellofemoral ligament reconstruction (MPFLR) with or without tibial tubercle osteotomy (TTO) in treating recurrent or habitual patellar dislocation with an increased tibial tuberosity-trochlear groove (TT-TG) distance. Methods: We performed a literature search of the established medical databases Cochrane Central, PubMed-MEDLINE, EMBASE, and Web of Science. The inclusion criteria were as follows: skeletally mature patients with recurrent or habitual patellar dislocation and an increased TT-TG distance, treatment with MPFLR combined with a TTO procedure or isolated MPFLR, and reporting of clinical outcomes and complications. Each study was assessed for quality and the level of evidence. The general characteristics, indications, surgical techniques, TT-TG distance, clinical results, imaging evaluation findings, and complications of each study were recorded. Results: Nine studies consisting of 288 knees met the inclusion criteria. The average Coleman score was 71.56 (range, 5583). The threshold for an increased TT-TG distance ranged from 16 to 20 mm in the included studies. Similar good postoperative outcomes were reported in patients with an increased TT-TG distance treated with MPFLR with versus without a TTO procedure. The mean postoperative Lysholm score ranged from 75.0 to 94.7 (I2 = 87.6%) in the isolated MPFLR group and from 85.0 to 87.6 (I2 = 16.3%) in the TTO-with-MPFLR group. Similar postoperative congruence angles were reported in both groups. The postoperative redislocation rate ranged from 0% to 4.2% in the TTO-withMPFLR group, and no redislocation was found in the isolated MPFLR group. The postoperative apprehension sign was only reported in isolated MPFLR patients. Conclusions: The outcomes of MPFLR with or without TTO to treat recurrent or habitual patellar dislocation with an increased TT-TG distance appeared similar. However, this study was limited by the considerable heterogeneity, variety of techniques, variety of TT-TG distances, and variability in patella alta and trochlear dysplasia among the included studies. Level of Evidence: Level IV, systematic review of Level II to IV studies.

局灶性关节软骨缺损在运动医学领域较为常见,通常导致关节疼痛和功能障碍,由于软骨无血管、缺乏内源性修复细胞的特点,其自愈能力有限,若不及时治疗最终将发展为骨关节炎.手术一直是临床治疗关节软骨缺损的主要手段,按照外科修复技术主要分为姑息性手术、修复性手术、重建性手术和软骨替代性手术等四大类.本文主要就近年来有关以上不同外科手段治疗局灶性软骨缺损的适应证、优势、局限性及远期疗效等方面的进展情况进行综述.

膝关节的关节软骨损伤、半月板血供差区域的撕裂和交叉韧带断裂自愈能力差,且对损伤结构及其功能进行重建的挑战大,属于难治性运动创伤.膝关节难治性运动创伤的治疗一直是临床和基础研究的热点之一,现有的治疗方法尚存较大局限.近些年来,干细胞在运动医学领域中的应用研究越来越多,大量研究结果和临床实践均表明外周血来源的间充质干细胞在难治性运动创伤治疗中有一定的安全性和有效性.本文就外周血间充质干细胞在膝关节软骨、半月板和交叉韧带损伤这三种难治性运动创伤治疗中的应用研究进展进行总结.

Background: Tendon-bone healing is an important factor in determining the success of ligament reconstruction. With the development of biomaterials science, the tissue engineering scaffold plays an extremely important role in tendon-bone healing and bone tissue engineering. Materials and Methods: Electronic databases (PubMed, Embase, and the Web of Science) were systematically searched for relevant and qualitative studies published from 1 January 1990 to 31 December 2019. Only original articles that met eligibility criteria and evaluated the use of issue engineering scaffold especially biomaterials in tendon bone healing in vivo were selected for analysis. Results: The search strategy identified 506 articles, and 27 studies were included for full review including two human trials and 25 animal studies. Fifteen studies only used biomaterials like PLGA, collage, PCL, PLA, and PET as scaffolds to repair the tendon-bone defect, on this basis, the rest of the 11 studies using biological interventions like cells or cell factors to enhance the healing. The adverse events hardly ever occurred, and the tendon bone healing with tissue engineering scaffold was effective and superior, which could be enhanced by biological interventions. Conclusion: Although a number of tissue engineering scaffolds have been developed and applied in tendon bone healing, the researches are mainly focused on animal models which are with limitations in clinical application. Since the efficacy and safety of tissue engineering scaffold has been proved, and can be enhanced by biological interventions, substantial clinical trials remain to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical practice.

Background Unlike bone tissue, little progress has been made regarding cartilage regeneration, and many challenges remain. Furthermore, the key roles of cartilage lesion caused by traumas, focal lesion, or articular overstress remain unclear. Traumatic injuries to the meniscus as well as its degeneration are important risk factors for long-term joint dysfunction, degenerative joint lesions, and knee osteoarthritis (OA) a chronic joint disease characterized by degeneration of articular cartilage and hyperosteogeny. Nearly 50% of the individuals with meniscus injuries develop OA over time. Due to the limited inherent self-repair capacity of cartilage lesion, the Biomaterial drug-nanomedicine is considered to be a promising alternative. Therefore, it is important to elucidate the gene potential regeneration mechanisms and discover novel precise medication, which are identified through this study to investigate their function and role in pathogenesis. Methods We downloaded the mRNA microarray statistics GSE117999, involving paired cartilage lesion tissue samples from 12 OA patients and 12 patients from a control group. First, we analyzed these statistics to recognize the differentially expressed genes (DEGs). We then exposed the gene ontology (GO) annotation and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. Protein-protein interaction (PPI) networks were then constructed, from which we attained eight significant genes after a functional interaction analysis. Finally, we identified a potential nanomedicine attained from this assay set, using a wide range of inhibitor information archived in the Search Tool for the Retrieval of Interacting Genes (STRING) database. Results Sixty-six DEGs were identified with our standards for meaning (adjusted P-value < 0.01, |log2 - FC| ≥1.2). Furthermore, we identified eight hub genes and one potential nanomedicine - Selenocysteine based on these integrative data. Conclusion We identified eight hub genes that could work as prospective biomarkers for the diagnostic and biomaterial drug treatment of cartilage lesion, involving the novel genes CAMP, DEFA3, TOLLIP, HLA-DQA2, SLC38A6, SLC3A1, FAM20A, and ANO8. Meanwhile, these genes were mainly associated with immune response, immune mediator induction, and cell chemotaxis. Significant support is provided for obtaining a series of novel gene targets, and we identify potential mechanisms for cartilage regeneration and final nanomedicine immunotherapy in regenerative medicine.

Osteochondral damage from trauma or osteoarthritis is a general joint disease that can lead to an increased social and economic burden in the modern society. The inefficiency of osteochondral defects is mainly due to the absence of suitable tissue-engineered substrates promoting tissue regeneration and replacing damaged areas. The hydrogels are becoming a promising kind of biomaterials for tissue regeneration. The biomimetic hydrogel microenvironment can be tightly controlled by modulating a number of biophysical and biochemical properties, including matrix mechanics, degradation, microstructure, cell adhesion, and intercellular interactions. In particular, advances in stem cell-laden hydrogels have offered new ideas for the cell therapy and osteochondral repair. Herein, the aim of this review is to underpin the importance of stem cell-laden hydrogels on promoting the development of osteochondral regeneration, especially in the field of manipulation of biomimetic microenvironment and utilization growth factors with various delivery methods.

Background Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear. Methods PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis. Results A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events. Conclusion Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.

Osteochondral damage from trauma or osteoarthritis is a general joint disease that can lead to an increased social and economic burden in the modern society. The inefficiency of osteochondral defects is mainly due to the absence of suitable tissue-engineered substrates promoting tissue regeneration and replacing damaged areas. The hydrogels are becoming a promising kind of biomaterials for tissue regeneration. The biomimetic hydrogel microenvironment can be tightly controlled by modulating a number of biophysical and biochemical properties, including matrix mechanics, degradation, microstructure, cell adhesion, and intercellular interactions. In particular, advances in stem cell-laden hydrogels have offered new ideas for the cell therapy and osteochondral repair. Herein, the aim of this review is to underpin the importance of stem cell-laden hydrogels on promoting the development of osteochondral regeneration, especially in the field of manipulation of biomimetic microenvironment and utilization growth factors with various delivery methods.

Human endometrial stem cells (hEnSCs), dental pulp stem cells (hDPSCs) and adipose tissue-derived stem cells (hADSCs) are considered to be the promising candidates for the treatment of pancreas diseases. The prognosis is better within situinjection of mesenchymal stem cells (MSCs) to the damaged pancreas compared with intravenous injection. However, the clinical application of these cells are limited, due to poor engraftment of transplanted cells after delivery. On the other hand, understanding the role of the biomaterials in cell therapy is essential to promote the therapeutic effects of MSCs. Matrigel, a basement membrane matrix biomaterial, is rich in laminin and collagen IV. The aim of this study is to investigate the difference of biological characteristics of hEnSCs, hDPSCs and hADSCsin vitroand their survival situation with Matrigel post intrapancreatic transplantationin vivo. Our findings showed, firstly, there was no significant difference in morphology and immunophenotype of these MSCs. Secondly, the biological properties, including cell proliferation, the ability of adipogenic and osteogenic differentiation and the mRNA expression levels of pancreas development-related genes, have been showed distinct difference among these MSCs. Thirdly, Matrigel can improve the survival of MSCsin vivo, especially for Matrigel-based hDPSCs and Matrigel-based hEnSCs in pancreas parenchyma of SD rats. These results suggest that hDPSCs and hEnSCs are with the greater inherent therapeutic potential for pancreas diseases compared with hADSCs.

BackgroundFew studies have investigated whether the mini-medial parapatellar (MMP) and quadriceps-sparing (QS) approaches have good long-term results compared to the conventional medial parapatellar (MP) approach in terms of clinical evaluations and radiographic assessments for total knee arthroplasty (TKA). The purpose of this study was to perform comparisons among the MMP, QS and MP approaches with a follow-up at 10 to 17 years.MethodsThis is a retrospective comparative study of 93 patients who underwent MMP TKA (32 TKAs), QS TKA (47 TKAs) or MP TKA (31 TKAs) with the same arthroplasty system. The clinical evaluations were performed according to the new American Knee Society score (KSS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the visual analogue scale (VAS), range of motion (ROM), incidence of anterior knee pain (AKP), the Feller patellofemoral score (PFS), the reoperation rate and the complication rates. Radiographic assessments included observation of the mechanical axis of the lower limb and calculations of the lateral distal femoral angle (LDFA), femoral flexion angle (FFA), medial proximal tibial angle (MPTA), tibial slope angle (TSA), lateral patella displacement (LPD), and lateral patella tilt (LPT).ResultsThere were no differences in the long-term follow-up results of the new KSS, WOMAC score, ROM, VAS, patellofemoral functions, reoperation rate or complication rates among the groups. In addition, no radiographic differences in terms of lower limb mechanical axis or femoral, tibial or patellar position were observed.ConclusionThese results provide conclusive evidence that equivalent, long-term clinical results can be obtained using any one of these three approaches.