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1.
Small ; : e2310024, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177175

RESUMEN

Bone matrix exhibits exceptional mechanical properties due to its unique nanocomposite structure of type I collagen fibrils and hydroxyapatite (HAp) nanoparticles in hierarchical liquid crystalline (LC) order. However, the regeneration mechanism of this LC structure is elusive. This study investigates the role of the LC structure of HAp nanorods in guiding aligned mineralization and its underlying molecular mechanism. A unidirectionally oriented LC phase of HAp nanorods is developed through engineering-assisted self-assembling. This is used to study the growth direction of long-range aligned extracellular matrix (ECM) and calcium deposit formation during the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. It is found that 2 key regulatory genes, COL1A1 and COL4A6, lead to the formation of aligned ECM. Activation of the PI3K-Akt pathway enhances osteogenesis and promotes ordered calcium deposits. This study provides evidence for elucidating the mechanism of LC-induced ordered calcium deposition at hierarchical levels spanning from the molecular to macro-scale, as well as the switch from ordered to disordered mineralization. These findings illuminate bone regeneration, contribute to the development of biomimetic artificial bone with long-range ordered structures, and suggest a basis for therapeutic targeting of microstructure-affected bone disorders and the broader field of cell-ECM interactions.

2.
Surg Endosc ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160304

RESUMEN

INTRODUCTION: Minimally invasive endoscopic options are safe and effective alternatives to surgery for the treatment of symptomatic Zenker's diverticulum (ZD). However, there is no consensus on the gold-standard approach. We compared the safety and efficacy of Zenker's peroral endoscopic myotomy (Z-POEM), flexible diverticulotomy (FD), and rigid diverticulotomy (RD) for the management of ZD. METHODS: Patients undergoing treatment for ZD at three UK tertiary referral centres were identified and analysed between 2013 and 2023. Patient demographics, procedural details, clinical success, and 30-day adverse events (AE) were recorded. The primary outcomes were technical and clinical success defined as a fall in Dakkak and Bennett dysphagia score to ≤ 1 without re-intervention. RESULTS: There was no difference in baseline characteristics amongst 126 patients undergoing intervention (50 RD, 31 FD, 45 Z-POEM). Technical success for RD, FD, and Z-POEM was 80%, 100%, and 100%, respectively (p < 0.001). Over a mean follow-up of 11.0 months (95% CI 8.2-13.9), clinical success amongst those treated was 85.3% (RD), 74.1% (FD), and 83.7% (Z-POEM; p = 0.48) with recurrence in 17.2% (RD), 20.0% (FD), and 8.3% (Z-POEM; p = 0.50). AEs were equivalent between groups (p = 0.98). During this time, 11 patients underwent surgical myotomy with low clinical success (36.4%) and high morbidity. CONCLUSION: Endoscopic options for the treatment of ZD show equivalent rates of success, but failed RD often led to open myotomy with worse outcomes. Flexible endoscopic modalities are both safe and highly effective treatments that may be considered first-line in experienced centres and should be offered before surgery.

3.
Am J Med Genet C Semin Med Genet ; 187(4): 527-532, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34799986

RESUMEN

A small number of case reports and observational studies describe chronic nasal congestion, upper airway obstruction, dysphonia, vocal cord abnormalities, and swallowing abnormalities in the Ehlers-Danlos syndromes. Little is known of the causes and therefore treatments of these, yet they are not uncommon findings in persons with hypermobility-related conditions presenting in the healthcare setting. We have a specialist multidisciplinary ear, nose, and throat and speech therapy practice with accumulating observational and empirical experience of managing these conditions, which include altered voice, choking, high dysphagia and anterior and deep neck pains. Here, we present our experience, some illustrative cases, and suggestions for future work in this evolving field.


Asunto(s)
Síndrome de Ehlers-Danlos , Inestabilidad de la Articulación , Bases de Datos Genéticas , Humanos , Inestabilidad de la Articulación/etiología , Faringe
4.
Eur Respir J ; 55(6)2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32444408

RESUMEN

Current methods to replace damaged upper airway epithelium with exogenous cells are limited. Existing strategies use grafts that lack mucociliary function, leading to infection and the retention of secretions and keratin debris. Strategies that regenerate airway epithelium with mucociliary function are clearly desirable and would enable new treatments for complex airway disease.Here, we investigated the influence of the extracellular matrix (ECM) on airway epithelial cell adherence, proliferation and mucociliary function in the context of bioengineered mucosal grafts. In vitro, primary human bronchial epithelial cells (HBECs) adhered most readily to collagen IV. Biological, biomimetic and synthetic scaffolds were compared in terms of their ECM protein content and airway epithelial cell adherence.Collagen IV and laminin were preserved on the surface of decellularised dermis and epithelial cell attachment to decellularised dermis was greater than to the biomimetic or synthetic alternatives tested. Blocking epithelial integrin α2 led to decreased adherence to collagen IV and to decellularised dermis scaffolds. At air-liquid interface (ALI), bronchial epithelial cells cultured on decellularised dermis scaffolds formed a differentiated respiratory epithelium with mucociliary function. Using in vivo chick chorioallantoic membrane (CAM), rabbit airway and immunocompromised mouse models, we showed short-term preservation of the cell layer following transplantation.Our results demonstrate the feasibility of generating HBEC grafts on clinically applicable decellularised dermis scaffolds and identify matrix proteins and integrins important for this process. The long-term survivability of pre-differentiated epithelia and the relative merits of this approach against transplanting basal cells should be assessed further in pre-clinical airway transplantation models.


Asunto(s)
Colágeno , Matriz Extracelular , Laminina , Mucosa Respiratoria , Andamios del Tejido , Animales , Bronquios , Células Cultivadas , Células Epiteliales , Humanos , Conejos
5.
Clin Otolaryngol ; 44(4): 497-501, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30834711

RESUMEN

Vocal fold nodules present the voice clinic team with a number of clinical dilemmas which are not as simple as previously thought. The definition, aetiology, prevalence and diagnosis are all poorly understood. Furthermore, treatment evidence for both behavioural and surgical approaches is weak. This paper reviews the published evidence pertaining to all of these aspects. Specific areas of uncertainty that remain include poorly defined nomenclature, the natural history of paediatric vocal nodules, the establishment of criteria to measure successful treatment, optimal configuration of speech therapy regimens and the rationale for surgical intervention. The authors suggest the development of evidence-based guidelines for UK practice.


Asunto(s)
Enfermedades de la Laringe/terapia , Pliegues Vocales , Humanos , Enfermedades de la Laringe/diagnóstico , Enfermedades de la Laringe/epidemiología , Enfermedades de la Laringe/etiología , Prevalencia , Factores de Riesgo
6.
Eur Radiol ; 27(2): 598-606, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27085701

RESUMEN

OBJECTIVE: Determine feasibility of vocal fold (VF) abduction and adduction assessment by cine magnetic resonance imaging (cine-MRI) METHODS: Cine-MRI of the VF was performed on five healthy and nine unilateral VF paralysis (UVFP) participants using an axial gradient echo acquisition with temporal resolution of 0.7 s. VFs were continuously imaged with cine-MRI during a 10-s period of quiet respiration and phonation. Scanning was repeated twice within an individual session and then once again at a 1-week interval. Asymmetry of VF position during phonation (VF phonation asymmetry, VFPa) and respiration (VF respiration asymmetry, VFRa) was determined. Percentage reduction in total glottal area between respiration and phonation (VF abduction potential, VFAP) was derived to measure overall mobility. An un-paired t-test was used to compare differences between groups. Intra-session, inter-session and inter-reader repeatability of the quantitative metrics was evaluated using intraclass correlation coefficient (ICC). RESULTS: VF position asymmetry (VFPa and VFRa) was greater (p=0.012; p=0.001) and overall mobility (VFAP) was lower (p=0.008) in UVFP patients compared with healthy participants. ICC of repeatability of all metrics was good, ranged from 0.82 to 0.95 except for the inter-session VFPa (0.44). CONCLUSION: Cine-MRI is feasible for assessing VF abduction and adduction. Derived quantitative metrics have good repeatability. KEY POINTS: • Cine-MRI is used to assess vocal folds (VFs) mobility: abduction and adduction. • New quantitative metrics are derived from VF position and abduction potential. • Cine-MRI able to depict the difference between normal and abnormal VF mobility. • Cine-MRI derived quantitative metrics have good repeatability.


Asunto(s)
Imagen por Resonancia Cinemagnética/métodos , Parálisis de los Pliegues Vocales/diagnóstico por imagen , Pliegues Vocales/diagnóstico por imagen , Adulto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Fonación , Reproducibilidad de los Resultados
7.
Am J Respir Crit Care Med ; 194(2): 156-68, 2016 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-26840431

RESUMEN

RATIONALE: Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell-seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts. OBJECTIVES: To define a scalable cell culture system to deliver airway epithelium to clinical grafts. METHODS: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T3+Y). Cells were analyzed by immunofluorescence, quantitative polymerase chain reaction, and flow cytometry to assess airway stem cell marker expression. Karyotyping and multiplex ligation-dependent probe amplification were performed to assess cell safety. Differentiation capacity was tested in three-dimensional tracheospheres, organotypic cultures, air-liquid interface cultures, and an in vivo tracheal xenograft model. Ciliary function was assessed in air-liquid interface cultures. MEASUREMENTS AND MAIN RESULTS: 3T3-J2 feeder cells and ROCK inhibition allowed rapid expansion of airway basal cells. These cells were capable of multipotent differentiation in vitro, generating both ciliated and goblet cell lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated tracheal scaffolds in a heterotopic transplantation xenograft model. CONCLUSIONS: Our method generates large numbers of functional airway basal epithelial cells with the efficiency demanded by clinical transplantation, suggesting its suitability for use in tracheal reconstruction.


Asunto(s)
Células Epiteliales/metabolismo , Enfermedades Respiratorias/terapia , Células Madre/metabolismo , Ingeniería de Tejidos/métodos , Diferenciación Celular/fisiología , Células Cultivadas , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Depuración Mucociliar/fisiología , Reacción en Cadena de la Polimerasa , Mucosa Respiratoria/fisiología
8.
J Cell Biochem ; 117(7): 1497-505, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26853803

RESUMEN

An ideal tracheal scaffold must withstand luminal collapse yet be flexible, have a sufficient degree of porosity to permit vascular and cellular ingrowth, but also be airtight and must facilitate growth of functional airway epithelium to avoid infection and aid in mucocilliary clearance. Finally, the scaffold must also be biocompatible to avoid implant rejection. Over the last 40 years, efforts to design and manufacture the airway have been undertaken worldwide but success has been limited and far apart. As a result, tracheal resection with primary repair remains the Gold Standard of care for patients presenting with airway disorders and malignancies. However, the maximum resectable length of the trachea is restricted to 30% of the total length in children or 50% in adults. Attempts to provide autologous grafts for human application have also been disappointing for a host of different reasons, including lack of implant integration, insufficient donor organs, and poor mechanical strength resulting in an unmet clinical need. The two main approaches researchers have taken to address this issue have been the development of synthetic scaffolds and the use of decellularized organs. To date, a number of different decellularization techniques and a variety of materials, including polyglycolic acid (PGA) and nanocomposite polymers have been explored. The findings thus far have shown great promise, however, there remain a significant number of caveats accompanying each approach. That being said, the possibilities presented by these two approaches could be combined to produce a highly successful, clinically viable hybrid scaffold. This article aims to highlight advances in airway tissue engineering and provide an overview of areas to explore and utilize in accomplishing the aim of developing an ideal tracheal prosthesis. J. Cell. Biochem. 117: 1497-1505, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Órganos Artificiales , Sistema Respiratorio , Ingeniería de Tejidos , Andamios del Tejido , Animales , Humanos , Neoplasias del Sistema Respiratorio/metabolismo , Neoplasias del Sistema Respiratorio/terapia , Ingeniería de Tejidos/métodos , Ingeniería de Tejidos/tendencias
9.
Proc Natl Acad Sci U S A ; 110(35): 14360-5, 2013 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-23940349

RESUMEN

Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissue-engineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cell-mediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.


Asunto(s)
Músculo Esquelético/inmunología , Andamios del Tejido , Trasplante Heterólogo , Animales , Proliferación Celular , Citocinas/inmunología , Regulación hacia Abajo , Matriz Extracelular , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Macrófagos/inmunología , Músculo Esquelético/citología , Conejos
10.
J Mater Sci Mater Med ; 26(3): 141, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25737129

RESUMEN

Children suffer from damaged or loss of hollow organs i.e. trachea, oesophagus or arteries from birth defects or diseases. Generally these organs possess an outer matrix consisting of collagen, elastin, and cells such as smooth muscle cells (SMC) and a luminal layer consisting of endothelial or epithelial cells, whilst presenting a barrier to luminal content. Tissue engineering research enables the construction of such organs and this study explores this possibility with a bioabsorbable nanocomposite biomaterial, polyhedral oligomeric silsesquioxane poly(ε-caprolactone) urea urethane (POSS-PCL).Our established methods of tubular graft extrusion were modified using a porogen-incorporated POSS-PCL and a new lamination method was explored. Porogen (40, 60 or 105 µm) were introduced to POSS-PCL, which were fabricated into a bilayered, dual topography matching the exterior and luminal interior of tubular organs. POSS-PCL with different amounts of porogen were tested for their suitability as a SMC layer by measuring optimal interactions with human adipose derived stem cells. Angiogenesis potential was tested with the chorioallantoic membrane assay. Tensile strength and burst pressures of bilayared tubular grafts were determined. Scaffolds made with 40 µm porogen demonstrated optimal adipose derived stem cell integration and the scaffolds were able to accommodate angiogenesis. Mechanical properties of the grafts confirmed their potential to match the relevant physiological and biophysical parameters. This study presents a platform for the development of hollow organs for transplantation based on POSS-PCL. These bilayered-tubular structures can be tailor-made for cellular integration and match physico-mechanical properties of physiological systems of interest. More specific luminal cell integration and sources of SMC for the external layer could be further explored.


Asunto(s)
Andamios del Tejido , Células Cultivadas , Niño , Humanos
11.
Lancet ; 391(10123): 883-910, 2018 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-28987452
12.
Cytotherapy ; 16(12): 1601-13, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25457172

RESUMEN

There has been significant and exciting recent progress in the development of bioengineering approaches for generating tracheal tissue that can be used for congenital and acquired tracheal diseases. This includes a growing clinical experience in both pediatric and adult patients with life-threatening tracheal diseases. However, not all of these attempts have been successful, and there is ongoing discussion and debate about the optimal approaches to be used. These include considerations of optimal materials, particularly use of synthetic versus biologic scaffolds, appropriate cellularization of the scaffolds, optimal surgical approaches and optimal measure of both clinical and biologic outcomes. To address these issues, the International Society of Cell Therapy convened a first-ever meeting of the leading clinicians and tracheal biologists, along with experts in regulatory and ethical affairs, to discuss and debate the issues. A series of recommendations are presented for how to best move the field ahead.


Asunto(s)
Bioprótesis , Ingeniería de Tejidos , Andamios del Tejido , Tráquea , Enfermedades de la Tráquea/terapia , Adulto , Animales , Congresos como Asunto , Francia , Humanos , Ingeniería de Tejidos/métodos , Ingeniería de Tejidos/tendencias
13.
Nanomedicine ; 10(1): 235-46, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23792331

RESUMEN

Auricular reconstruction using sculpted autologous costal cartilage is effective, but complex and time consuming and may incur donor site sequelae and morbidity. Conventional synthetic alternatives are associated with infection and extrusion in up to about 15% of cases. We present a novel POSS-PCU nanocomposite auricular scaffold, which aims to reduce extrusion rates by mimicking the elastic modulus of human ears and by encouraging desirable cellular interactions. The fabrication, physicochemical properties (including nanoscale topography) and cellular interactions of these scaffolds were compared to Medpor®, the current synthetic standard. Our scaffold had a more similar elastic modulus (5.73 ± 0.17MPa) to ear cartilage (5.02 ± 0.17MPa) compared with Medpor®, which was much stiffer (140.9 ± 0.04MPa). POSS-PCU supported fibroblast ingrowth and proliferation; significantly higher collagen production was also produced by cells on the POSS-PCU than those on Medpor®. This porous POSS-PCU nanocomposite scaffold is therefore a promising alternative biomaterial for auricular surgical reconstruction. FROM THE CLINICAL EDITOR: In this paper, a novel POSS-PCU nanocomposite auricular scaffold is described to reduce extrusion rates by having a much closer elastic modulus of human ears than the currently available synthetic standard. Enabling desirable cellular interactions may lead to the successful clinical application of these novel scaffolds.


Asunto(s)
Cartílago Auricular/química , Nanocompuestos/uso terapéutico , Procedimientos de Cirugía Plástica , Andamios del Tejido , Materiales Biocompatibles/química , Oído/cirugía , Cartílago Auricular/trasplante , Humanos , Nanocompuestos/química , Compuestos de Organosilicio/química , Compuestos de Organosilicio/uso terapéutico , Polietilenos/química , Polietilenos/uso terapéutico , Prótesis e Implantes
14.
Mod Rheumatol ; 24(3): 434-42, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24252027

RESUMEN

OBJECTIVES: While numerical and functional defects of invariant NKT cells have been demonstrated in rheumatoid arthritis (RA), the detailed characterization of proliferative and secretory responses following CD1d-mediated presentation is lacking; the presence of non-invariant populations has never been assessed in human autoimmunity. We have evaluated both invariant and non-invariant populations in the blood and synovial fluid from patients to assess feasibility of NKT cell-directed manipulations in RA. METHODS: NKT cell populations were quantified by anti-CD4/anti-Vα24 staining and/or CD1d tetramers. Proliferation was measured in cultures of mononuclear cells following stimulations with αGalCer and cytokine secretion determined by multi-bead assay. RESULTS: We have confirmed a proliferative defect of iNKT cells in both peripheral blood and synovial fluid from RA patients, but no changes in baseline frequencies. Moreover, we have detected an enlargement of non-invariant cell pool in synovial fluid samples. In addition, we noted an evident Th2 shift following exposure to αGalCer and pronounced IL-6 secretion. CONCLUSIONS: While RA patients suffer from defective proliferative responses of invariant NKT cells, non-invariant cells accumulate at the site of inflammation. While stimulation with αGalCer results in reduced TNF-α and increased suppressive IL-10, abundantly produced IL-6 could potentially contribute to the induction of Th17 cells in the joints.


Asunto(s)
Artritis Reumatoide/inmunología , Articulaciones/inmunología , Células T Asesinas Naturales/inmunología , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Antígenos CD4/metabolismo , Proliferación Celular , Citocinas/metabolismo , Humanos , Articulaciones/metabolismo , Articulaciones/patología , Células T Asesinas Naturales/metabolismo , Células T Asesinas Naturales/patología , Líquido Sinovial/inmunología , Líquido Sinovial/metabolismo
15.
J Voice ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38849232

RESUMEN

OBJECTIVES: This scoping review aims to comprehensively assess current surgical interventions for bilateral vocal fold paralysis (BVFP), addressing the heterogeneity in treatment outcomes. Additionally, it explores the potential role of soft robotics as an innovative approach to improve outcomes in BVFP management. METHODS: This scoping review systematically examines literature from MEDLINE, Embase, and Scopus databases. Inclusion criteria encompass studies related to BVFP management with measurable subjective or objective outcomes. Studies with populations solely under the age of 18 were excluded. Four reviewers independently screened 2263 studies, resulting in the selection of 125 papers for data extraction. Information included study characteristics, interventions, and outcomes. Data synthesis involved both quantitative and qualitative analyses. RESULTS: The review identified 145 surgical interventions grouped into seven types: tracheostomy, cordectomy, arytenoidectomy, lateralization, combined procedures and others. Outcome measures fit into the following categories: "objective voice," "subjective voice," "aerodynamics," "dyspnea," "decannulation," "swallow," and "quality of life." Positive outcomes were predominant across all interventions, with arytenoidectomy and cordectomy showing relatively lower rates of successful objective and subjective voice outcomes. This could be the result of prioritizing improved airway status. Soft robotics is hypothesized as a potential solution to the limitation of current interventions sacrificing voice for breathing. CONCLUSIONS: The main aim of current surgical interventions for BVFP is expanding glottic aperture. Yet achieving optimal outcomes remains elusive due to complex airflow dynamics and potential impacts on phonatory function and swallowing. The current review underscores the need for a more nuanced, personalized approach, considering individual anatomical and physiological variations. Soft robotics emerges as a promising avenue to address this variability. However, challenges such as implantation procedures, long-term care, and patient education require careful consideration. Collaboration between medical professionals, engineers, and robotics specialists is essential for translating these principles into practical solutions.

16.
ACS Appl Mater Interfaces ; 16(15): 19480-19495, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38581369

RESUMEN

Light-driven soft actuators based on photoresponsive materials can be used to mimic biological motion, such as hand movements, without involving rigid or bulky electromechanical actuations. However, to our knowledge, no robust photoresponsive material with desireable mechanical and biological properties and relatively simple manufacture exists for robotics and biomedical applications. Herein, we report a new visible-light-responsive thermoplastic elastomer synthesized by introducing photoswitchable moieties (i.e., azobenzene derivatives) into the main chain of poly(ε-caprolactone) based polyurethane urea (PAzo). A PAzo elastomer exhibits controllable light-driven stiffness softening due to its unique nanophase structure in response to light, while possessing excellent hyperelasticity (stretchability of 575.2%, elastic modulus of 17.6 MPa, and strength of 44.0 MPa). A bilayer actuator consisting of PAzo and polyimide films is developed, demonstrating tunable bending modes by varying incident light intensities. Actuation mechanism via photothermal and photochemical coupling effects of a soft-hard nanophase is demonstrated through both experimental and theoretical analyses. We demonstrate an exemplar application of visible-light-controlled soft "fingers" playing a piano on a smartphone. The robustness of the PAzo elastomer and its scalability, in addition to its excellent biocompatibility, opens the door to the development of reproducible light-driven wearable/implantable actuators and lightweight soft robots for clinical applications.


Asunto(s)
Elastómeros , Robótica , Elastómeros/química , Poliuretanos , Urea
17.
Nanoscale ; 16(31): 14802-14812, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39028306

RESUMEN

Macromolecule branching upon polyhedral oligomeric silsesquioxanes (POSS) via "click" chemistry has previously been reported for promoting natural biological responses in vitro, particularly when regarding their demonstrated biocompatibility and structural robustness as potential macromolecule anchoring points. However, "clicking" of large molecules around POSS structures uncovers two main challenges: (1) a synthetic challenge encompassing multi-covalent attachment of macromolecules to a single nanoscale-central position, and (2) purification and separation of fully adorned nanocages from those that are incomplete due to their similar physical characteristics. Here we present peptide decoration to a T8POSS nanocage through the attachment of azido-modified trimers. Triglycine- and trialanine-methyl esters "clicked" to 97% and 92% completion, respectively, resulting in 84% and 68% yields of the fully-adorned octamers. The "clicks" halt within 27-h of the reaction time, and efforts to further increase the octamer yield were of negligible benefit. Exploration of reaction conditions reveals multiple factors preventing full octa-arm modification to all available POSS nanocages, and offers insights into macromolecule attachment between both peptides and small inorganic-organic structures, all of which require consideration for future work of this nature.


Asunto(s)
Química Clic , Compuestos de Organosilicio , Péptidos , Péptidos/química , Compuestos de Organosilicio/química , Nanoestructuras/química , Azidas/química
18.
J Voice ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39138040

RESUMEN

OBJECTIVE: Laryngeal dystonia (LD), previously termed spasmodic dysphonia, is an isolated focal dystonia that involves involuntary, uncontrolled contractions of the laryngeal muscles during speech. It is a severely disabling condition affecting patients' work and social lives through prevention of normal speech production. Our understanding of the pathophysiology of LD and available therapeutic options are currently limited. The aim of this short review is to provide an up-to-date summary of what is known about the central mechanisms and the pathophysiology of LD. METHODS: A systematic review of the literature was performed searching Embase, CINHAL, Medline, and Cochrane with the cover period January 1990-October 2023 with a search strategy (("Laryngeal dystonia" OR "Spasmodic dysphonia") AND ("Central Mechanism" OR "Pathophysiology")). Original studies involving LD patients that discussed central mechanisms and/or pathophysiology of LD were chosen. RESULTS: Two hundred twenty-six articles were identified of which 27 articles were included to formulate this systematic review following the screening inclusion and exclusion criteria. LD is a central neurological disorder involving a multiregional altered neural network. Affected neural circuits not only involve the motor control circuit, but also the feedforward, and the feedback circuits of the normal speech production neural network, involving higher-order planning, somatosensory perception and integration regions of the brain. CONCLUSION: Speech production is a complex process, and LD is a central neurological disorder involving multiregional neural network connectivity alteration reflecting this. Neuromodulation targeting the central nervous system could therefore be considered and explored as a new potential therapeutic option for LD in the future, and should assist in elucidating the underlying central mechanisms responsible for causing the condition.

19.
Laryngoscope ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970445

RESUMEN

BACKGROUND: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss. OBJECTIVE: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally. METHODOLOGY: A case series. Patients were enrolled retrospectively by each institutional hospital or clinic. Eleven patients with complete loss of laryngeal function undergoing total laryngeal transplantation between 1998 and 2018 were recruited. RESULTS: After a minimum of 24 months follow-up, three patients had died (27%), and there were two graft explants in survivors, one total and one partial, due to chronic rejection. In the remaining cases, voice was functional in 62.5% and 50% achieved decannulation. Swallowing was initially restricted, but only one patient was gastrostomy-dependent by 6 months and all had normal or near-normal swallowing by the end of year two after transplantation. Median follow-up was 73 months. Functional (voice, swallowing, airway) recovery peaked between 12 and 24 months. CONCLUSIONS: Laryngeal transplantation is a complex procedure with significant morbidity. Significant improvements in quality of life are possible for highly selected individuals with end-stage laryngeal disorders, including laryngeal neoplasia, but further technical and pharmacological developments are required if the technique is to be more widely applicable. An international registry should be created to provide better quality pooled data for analysis of outcomes of any future laryngeal transplants. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

20.
Physiology (Bethesda) ; 27(3): 140-7, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22689789

RESUMEN

Human airways are a paragon of intrinsic engineering. They experience 7,000-10,000 liters of airflow/day, have a 70-m(2) surface area, and undergo complete renewal every 100-400 days. Despite this, airways are susceptible to aging, injury, and diseases that are major causes of mortality. Current airway regeneration research is focused both on understanding the cells and strategies responsible for maintaining intrinsic tissue homeostasis as well as on establishing clinical interventions for improving repair.


Asunto(s)
Bronquios/fisiología , Homeostasis/fisiología , Regeneración/fisiología , Fenómenos Fisiológicos Respiratorios , Tráquea/fisiología , Humanos , Cicatrización de Heridas/fisiología
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