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1.
Bioengineering (Basel) ; 10(11)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-38002366

RESUMEN

The expected outcome after a scaffold augmented hernia repair is the regeneration of a tissue composition strong enough to sustain biomechanical function over long periods. It is hypothesised that melt electrowriting (MEW) medical-grade polycaprolactone (mPCL) scaffolds loaded with platelet-rich plasma (PRP) will enhance soft tissue regeneration in fascial defects in abdominal and vaginal sheep models. A pre-clinical evaluation of vaginal and abdominal hernia reconstruction using mPCL mesh scaffolds and polypropylene (PP) meshes was undertaken using an ovine model. Each sheep was implanted with both a PP mesh (control group), and a mPCL mesh loaded with PRP (experimental group) in both abdominal and vaginal sites. Mechanical properties of the tissue-mesh complexes were assessed with plunger tests. Tissue responses to the implanted meshes were evaluated via histology, immunohistochemistry and histomorphometry. At 6 months post-surgery, the mPCL mesh was less stiff than the PP mesh, but stiffer than the native tissue, while showing equitable collagen and vascular ingrowth when compared to PP mesh. The results of this pilot study were supportive of mPCL as a safe and effective biodegradable scaffold for hernia and vaginal prolapse repair, hence a full-scale long-term study (over 24-36 months) with an adequate sample size is recommended.

2.
Pharmaceutics ; 15(5)2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37242582

RESUMEN

This study leverages the advantages of two fabrication techniques, namely, melt-extrusion-based 3D printing and porogen leaching, to develop multiphasic scaffolds with controllable properties essential for scaffold-guided dental tissue regeneration. Polycaprolactone-salt composites are 3D-printed and salt microparticles within the scaffold struts are leached out, revealing a network of microporosity. Extensive characterization confirms that multiscale scaffolds are highly tuneable in terms of their mechanical properties, degradation kinetics, and surface morphology. It can be seen that the surface roughness of the polycaprolactone scaffolds (9.41 ± 3.01 µm) increases with porogen leaching and the use of larger porogens lead to higher roughness values, reaching 28.75 ± 7.48 µm. Multiscale scaffolds exhibit improved attachment and proliferation of 3T3 fibroblast cells as well as extracellular matrix production, compared with their single-scale counterparts (an approximate 1.5- to 2-fold increase in cellular viability and metabolic activity), suggesting that these structures could potentially lead to improved tissue regeneration due to their favourable and reproducible surface morphology. Finally, various scaffolds designed as a drug delivery device were explored by loading them with the antibiotic drug cefazolin. These studies show that by using a multiphasic scaffold design, a sustained drug release profile can be achieved. The combined results strongly support the further development of these scaffolds for dental tissue regeneration applications.

3.
BMJ Support Palliat Care ; 13(4): 453-461, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34479960

RESUMEN

BACKGROUND: Several studies have suggested that sarcopenia is associated with an increased treatment toxicity in patients with cancer. The aim of this study is to evaluate the relationship between sarcopenia and anthracycline-related cardiotoxicity. METHODS: Patients who received anthracycline-based chemotherapy between 2014 and 2018 and had baseline abdominal CT and baseline and follow-up echocardiography after anthracycline treatment were included. European Society of Cardiology ejection fraction criteria and American Society of Echocardiography diastolic dysfunction criteria were used for definition of cardiotoxicity. Sarcopenia was defined on the basis of skeletal muscle index (SMI) and psoas muscle index (PMI) calculated on CT images at L3 and L4 vertebra levels. RESULTS: A total of 166 patients (75 men and 91 women) were included. Sarcopenia was determined in 33 patients (19.9%) according to L3-SMI, in 17 patients (10.2%) according to L4-SMI and in 45 patients (27.1%) according to PMI. 27 patients (16.3%) developed cardiotoxicity. PMI and L3-SMI were significantly associated with an increased risk of cardiotoxicity (L3-SMI: HR=3.27, 95% CI 1.32 to 8.11, p=0.01; PMI: HR=3.71, 95% CI 1.58 to 8.73, p=0.003). CONCLUSIONS: This is the first study demonstrating a significant association between CT-diagnosed sarcopenia and anthracycline-related cardiotoxicity. Routine CT scans performed for cancer staging may help clinicians identify high-risk patients in whom closer follow-up or cardioprotective measures should be considered.


Asunto(s)
Neoplasias , Sarcopenia , Masculino , Humanos , Femenino , Sarcopenia/inducido químicamente , Sarcopenia/diagnóstico por imagen , Sarcopenia/complicaciones , Cardiotoxicidad/complicaciones , Antraciclinas/efectos adversos , Pronóstico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Músculos Psoas/diagnóstico por imagen , Estudios Retrospectivos
4.
Support Care Cancer ; 30(11): 9071-9078, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35972646

RESUMEN

AIM: The combination of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors plus endocrine therapy (ET) improved the survival outcomes and became the standard of care in the treatment of metastatic hormone-positive breast cancer. However, these combinations increased the risk of neutropenia compared with ET alone. While the infection-related mortalities did not seem to be increased, the exact risk of infections with CDK 4/6 inhibitor and ET combinations is relatively understudied. Therefore, we performed a meta-analysis of CDK 4/6 inhibitor clinical trials to assess the infection risk of adding CDK4/6 inhibitors to ET. MATERIAL AND METHOD: We systemically searched the PubMed database for relevant clinical trials. For each study, all grade and grade 3 or higher infections, upper respiratory tract infections (URTI), urinary tract infections (UTI), pneumonia, and febrile neutropenia rates were recorded whenever available. The hazard ratios (HR) with a 95% confidence interval (CI) of infection risk were calculated via the generic inverse-variance method with a random-effects model. RESULTS: Nine eligible studies were included in the analyses (MONALEESA-2,3,7, MONARCH-2,3, MONARCH plus, PALOMA-1,2,3). In the meta-analysis of these studies, CDK 4/6 inhibitors plus ET arms were associated with increased all grade infections (HR 1.77, 95% CI 1.56-2.01, p < 0.00001), grade 3 or higher infections, (HR 1.77, 95% CI 1.28-2.43, p = 0.0005), UTIs (HR 1.59, 95% CI 1.19-2.12, p = 0.002), and febrile neutropenia (HR 4.28, 95% CI 1.73-10.62, p = 0.002). CONCLUSION: In this meta-analysis, we observed that adding CDK4/6 inhibitors to ET significantly increased the risk of all grade, grade 3 or higher infections, and urinary tract infections. We propose that closer follow-up for infections should be considered for metastatic breast cancer patients using CDK 4/6 inhibitors. This may help clinicians to recognize infections earlier which prevents early death from infection.


Asunto(s)
Neoplasias de la Mama , Infecciones , Inhibidores de Proteínas Quinasas , Femenino , Humanos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Neutropenia Febril/etiología , Inhibidores de Proteínas Quinasas/efectos adversos , Infecciones/etiología
5.
Bone ; 158: 116018, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34023543

RESUMEN

Current xenograft animal models fail to accurately replicate the complexity of human bone disease. To gain translatable and clinically valuable data from animal models, new in vivo models need to be developed that mimic pivotal aspects of human bone physiology as well as its diseased state. Above all, an advanced bone disease model should promote the development of new treatment strategies and facilitate the conduction of common clinical interventional procedures. Here we describe the development and characterisation of an orthotopic humanised tissue-engineered osteosarcoma (OS) model in a recently genetically engineered x-linked severe combined immunodeficient (X-SCID) rat. For the first time in a genetically modified rat, our results show the successful implementation of an orthotopic humanised tissue-engineered bone niche supporting the growth of a human OS cell line including its metastatic spread to the lung. Moreover, we studied the inter- and intraspecies differences in ultrastructural composition of bone and calcified tissue produced by the tumour, pointing to the crucial role of humanised animal models.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Animales , Neoplasias Óseas/secundario , Huesos/patología , Línea Celular , Línea Celular Tumoral , Humanos , Osteosarcoma/tratamiento farmacológico , Ratas , Ingeniería de Tejidos
6.
Future Oncol ; 18(3): 323-331, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34758639

RESUMEN

Background: In node-negative HER2-overexpressed breast cancers, adjuvant paclitaxel plus trastuzumab treatment is a successful de-escalation approach with excellent survival outcomes. Methods: All patients with HER2+ breast cancer treated in our centers were retrospectively reviewed. Results: We analyzed 173 patients who were treated with adjuvant paclitaxel plus trastuzumab. The mean tumor size was 2.2 cm. There were eight invasive disease events or death: four distant recurrences (2.3%), three locoregional recurrences (1.7%) and one death without documented recurrence after a 52 month follow-up. The 3-year disease-free survival and recurrence-free interval rate was 96.6%. Conclusion: This real-life experience with adjuvant paclitaxel plus trastuzumab demonstrated few distant recurrences and is compatible with the APT trial findings.


Lay abstract In oncology practice, there have been some efforts to avoid the toxicity of combination chemotherapies and reduce the amount of treatment given in recent decades. These strategies have been studied especially for patients with a specific subtype of early-stage breast cancer. We present the results from patients treated in our centers and discuss them in relation to the literature.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/terapia , Recurrencia Local de Neoplasia/epidemiología , Paclitaxel/uso terapéutico , Trastuzumab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Mama/patología , Mama/cirugía , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Mastectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Receptor ErbB-2/análisis , Receptor ErbB-2/metabolismo , Estudios Retrospectivos
7.
Mater Sci Eng C Mater Biol Appl ; 128: 112313, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34474864

RESUMEN

Tissue engineering strategies are widely used to model and study the bone marrow microenvironment in healthy and pathological conditions. Yet, while bone function highly depends on mechanical stimulation, the effects of biomechanical stimuli on the bone marrow niche, specifically on bone marrow adipose tissue (BMAT) is poorly understood due to a lack of representative in vitro loading models. Here, we engineered a BMAT analog made of a GelMA (gelatin methacryloyl) hydrogel/medical-grade polycaprolactone (mPCL) scaffold composite to structurally and biologically mimic key aspects of the bone marrow microenvironment, and exploited an innovative bioreactor to study the effects of mechanical loading. Highly reproducible BMAT analogs facilitated the successful adipogenesis of human mesenchymal bone marrow stem cells. Upon long-term intermittent stimulation (1 Hz, 2 h/day, 3 days/week, 3 weeks) in the novel bioreactor, cellular proliferation and lipid accumulation were similar to unloaded controls, yet there was a significant reduction in the secretion of adipokines including leptin and adiponectin, in line with clinical evidence of reduced adipokine expression following exercise/activity. Ultimately, this innovative loading platform combined with reproducibly engineered BMAT analogs provide opportunities to study marrow physiology in greater complexity as it accounts for the dynamic mechanical microenvironment context.


Asunto(s)
Tejido Adiposo , Médula Ósea , Células de la Médula Ósea , Gelatina , Humanos , Ingeniería de Tejidos
8.
J Oncol Pharm Pract ; 27(5): 1281-1283, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33070764

RESUMEN

INTRODUCTION: Although, immune check-point inhibitors changed the course of many cancers, the outcomes in sarcomas were rather disappointing with less than 10% response rates. Ewing sarcoma is a poorly differentiated and aggressive tumor mostly seen in the children and adolescents. It's a distinct type of sarcoma with prominent chemosensitivity in the early stages. However, the relapsing disease has a poor prognosis with limited treatment options. CASE REPORT: Herein, we represent a case of relapsed Ewing sarcoma treated with multiple lines of chemotherapy.Management & outcome: The patient had a very good response to salvage treatment with a combination of paclitaxel and nivolumab which lasted for twelve months after the cessation of treatment. DISCUSSION: We think that chemotherapy plus immunotherapy can be an option for Ewing sarcoma patients treated with multiple lines of chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Adolescente , Humanos , Inmunoterapia , Masculino , Recurrencia Local de Neoplasia , Paclitaxel/uso terapéutico , Terapia Recuperativa
9.
Tissue Eng Part B Rev ; 27(1): 48-73, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32403989

RESUMEN

Described as a projection (prolapse) of tissue through a fascial defect in the abdominal wall, hernias are associated with significant rates of complications, recurrence, and reoperations. This literature review is aimed at providing an overview of the prosthetic surgical meshes used for the repairing of hernia defects. The review was carried out using two specialized online databases: Espacenet, from the European Patent Office (EPO), and WIPO from the World Intellectual Property Organization. Of the 56 patents selected from 2008 to 2018, China was the largest contributor with 55% (31 patents) of the total patent applicant filings, followed by the United States of America (US), with 29% (16 patents). Although the majority of patent applications (39 documents) had at least one company (industry) assigned to the patent application, 4 patents were solely from academic research. Our data showed that only 13 industry applicants have had their products included in the market, and the majority of meshes available on the market are still made from polypropylene. Chemical, physical, and mesh surface modifications have been implemented, and a few reviews describing mesh design, composition, and mechanical properties are available. However, to date, the ideal mesh implant from a clinical point of view has not been developed.


Asunto(s)
Hernia , Mallas Quirúrgicas , Humanos , Estados Unidos
10.
Acta Biomater ; 118: 69-82, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33039595

RESUMEN

In this study we developed and validated a 3D-printed drug delivery system (3DPDDS) to 1) improve local treatment efficacy of commonly applied chemotherapeutic agents in bone cancers to ultimately decrease their systemic side effects and 2) explore its concomitant diagnostic potential. Thus, we locally applied 3D-printed medical-grade polycaprolactone (mPCL) scaffolds loaded with Doxorubicin (DOX) and measured its effect in a humanized primary bone cancer model. A bioengineered species-sensitive orthotopic humanized bone niche was established at the femur of NOD-SCID IL2Rγnull (NSG) mice. After 6 weeks of in vivo maturation into a humanized ossicle, Luc-SAOS-2 cells were injected orthotopically to induce local growth of osteosarcoma (OS). After 16 weeks of OS development, a biopsy-like defect was created within the tumor tissue to locally implant the 3DPDDS with 3 different DOX loading doses into the defect zone. Histo- and morphological analysis demonstrated a typical invasive OS growth pattern inside a functionally intact humanized ossicle as well as metastatic spread to the murine lung parenchyma. Analysis of the 3DPDDS revealed the implants' ability to inhibit tumor infiltration and showed local tumor cell death adjacent to the scaffolds without any systemic side effects. Together these results indicate a therapeutic and diagnostic capacity of 3DPDDS in an orthotopic humanized OS tumor model.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Animales , Materiales Biocompatibles , Neoplasias Óseas/tratamiento farmacológico , Ratones , Ratones Endogámicos NOD , Ratones SCID , Osteosarcoma/tratamiento farmacológico , Impresión Tridimensional
11.
Artículo en Inglés | MEDLINE | ID: mdl-32850700

RESUMEN

The manufacture of fibrous scaffolds with tailored micrometric features and anatomically relevant three-dimensional (3D) geometries for soft tissue engineering applications remains a great challenge. Melt electrowriting (MEW) is an advanced additive manufacturing technique capable of depositing predefined micrometric fibers. However, it has been so far inherently limited to simple planar and tubular scaffold geometries because of the need to avoid polymer jet instabilities. In this work, we surmount the technical boundaries of MEW to enable the manufacture of complex fibrous scaffolds with simultaneous controlled micrometric and patient-specific anatomic features. As an example of complex geometry, aortic root scaffolds featuring the sinuses of Valsalva were realized. By modeling the electric field strength associated with the MEW process for these constructs, we found that the combination of a conductive core mandrel with a non-conductive 3D printed model reproducing the complex geometry minimized the variability of the electric field thus enabling the accurate deposition of fibers. We validated these findings experimentally and leveraged the micrometric resolution of MEW to fabricate unprecedented fibrous aortic root scaffolds with anatomically relevant shapes and biomimetic microstructures and mechanical properties. Furthermore, we demonstrated the fabrication of patient-specific aortic root constructs from the 3D reconstruction of computed tomography clinical data.

12.
Tissue Eng Part B Rev ; 26(3): 272-283, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32089089

RESUMEN

Reconstructive surgery aims to restore tissue defects by replacing them with similar autologous tissue to achieve good clinical outcomes. However, often the defect is too large or the tissue available is limited, requiring synthetic materials to restore the anatomical shape and partial function. The utilization of three-dimensional (3D) printing allows for the manufacture of implants with complex geometries and internal architecture that more closely matches the required clinical needs. Synthetic polymers offer certain advantages over natural polymers as biomedical materials due to their ability to more closely mimic the mechanical and chemical properties of the native tissue. Synthetic polymer materials such as poly(lactic acid) and acrylonitrile butadiene styrene are easily 3D printed to generate 3D objects due to their flexibility in their chemical and mechanical properties and physical form. Polyurethanes (PUs) are widely used as short- and long-term, implantable medical devices due to their good mechanical properties, biocompatibility, and hemocompatibility. This article provides an overview on the advancement of 3D printable PU-based materials for biomedical applications. A summary of the chemical structure and synthesis of PUs is provided to explain how PUs may be processed into medical devices using additive manufacturing techniques. Currently, PUs are being explored by several 3D printing approaches, including fused filament fabrication, bioplotting, and stereolithography, to fabricate complex implants with precise patterns and shapes with fine resolution. PU scaffolds using 3D printing have shown good cell viability and tissue integration in vivo. The important limitations of PU printing are identified to stimulate future research. PUs offer a biocompatible, synthetic polymeric material that can be 3D printed to manufacture implants that are tailored to meet specific anatomical, mechanical, and biological requirements for biomedical applications.


Asunto(s)
Tecnología Biomédica , Poliuretanos/química , Impresión Tridimensional , Animales , Líquidos Corporales/química , Humanos , Poliuretanos/síntesis química , Temperatura
13.
Tissue Eng Part A ; 26(5-6): 292-304, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31910098

RESUMEN

Stereolithography (SL) has several advantages over traditional biomanufacturing techniques such as fused deposition modeling, including increased speed, accuracy, and efficiency. While SL has been broadly used in tissue engineering for the fabrication of three-dimensional scaffolds that can mimic the in vivo environment for cell growth and tissue regeneration, lithographic printing is usually performed on single-component materials cured with ultraviolet light, severely limiting the versatility and cytocompatibility of such systems. In this study, we report a highly tunable, low-cost photoinitiator system that we used to establish a systematic library of crosslinked materials based on low molecular weight poly(ethylene glycol) diacrylate. We assessed the physicochemical properties, photocrosslinking efficiency, cost performance, and biocompatibility to demonstrate the capability of manufacturing a multimaterial complex tissue scaffold. [Figure: see text] Impact statement Stereolithography (SL) has advantages over traditional biomanufacturing techniques, including accuracy and efficiency. While SL has been broadly used for fabricating three-dimensional scaffolds that can mimic the in vivo environment for cell growth and tissue regeneration, lithographic printing is usually performed on single-component materials cured with ultraviolet light, severely limiting the versatility and cytocompatibility of such systems. In this study, we report a highly tunable photoinitiator system and establish a systematic library of crosslinked materials based on poly(ethylene glycol) diacrylate. We assessed the physicochemical properties, photocrosslinking efficiency and biocompatibility to demonstrate the capability of manufacturing a multimaterial complex tissue scaffold.


Asunto(s)
Luz , Polietilenglicoles/química , Materiales Biocompatibles/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
14.
ACS Macro Lett ; 9(12): 1732-1739, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-35653675

RESUMEN

Biodegradable coronary artery stents are sought-after alternatives to permanent stents. These devices are designed to degrade after the blood vessel heals, leaving behind a regenerated artery. The original generation of clinically available biodegradable stents required significantly thicker struts (∼150 µm) than nondegradable ones to ensure sufficient mechanical strength. However, these thicker struts proved to be a key contributor to the clinical failure of the stents. A current challenge lies in the fabrication of stents that possess both thin struts and adequate mechanical strength. In this contribution, we describe a method for the bottom-up, additive manufacturing of biodegradable composite stents with ultrathin fibers and superior mechanical properties compared to the base polymer. Specifically, we illustrate that melt electrowriting (MEW) can be used to 3D print composite structures with thin struts (60-80 µm) and a high degree of geometric complexity required for stenting applications. Additionally, this technology allows additive manufacture of personalized stents that are customized to a patient's unique anatomy and disease state. Furthermore, we illustrate that polycaprolactone-reduced graphene oxide nanocomposites have superior mechanical properties compared to original polycaprolactone without detriment to the material's cytocompatibility and that customizable stent-like structures can be fabricated from these materials with struts as thin as 60 µm, well below the target value for clinical use of 80 µm.

15.
J Oncol Pharm Pract ; 26(5): 1230-1233, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31735133

RESUMEN

INTRODUCTION: Immune checkpoint inhibitors and angiogenesis inhibitors are novel treatment options for renal cell carcinoma and widely used in clinical practice. They are related with adverse events that occur as a consequence of immune system activation and inhibition of angiogenesis. Herein, we report a rare case of inflammatory arthritis seen in a patient treated with an anti Programmed cell death-1 pembrolizumab and an anti-vascular endothelial growth factor pazopanib. CASE REPORT: A 60-year-old Caucasian male presented to our clinic with inflammatory arthritis with pitting edema. He had been started on pembrolizumab therapy for metastatic renal cell carcinoma after enrolling in the KEYNOTE-679 study. After six cycles of treatment with pembrolizumab, metastasis had been determined in the lung. Then, the patient's therapy was changed to pazopanib. While the patient was on pazopanib treatment, he noticed a gradual swelling of both hands. Rheumatoid factor, anti-nuclear antibody and anti-cyclic citrullinated peptide were negative. Joint ultrasonography revealed acute tenosynovitis and soft tissue swelling with pitting edema, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. Management and outcome: He was started on 10 mg prednisolone daily. His symptoms dramatically responded to corticosteroid. He continued to take pazopanib. Then, the patient was discharged with 10 mg prednisolone daily. DISCUSSION: Pembrolizumab- and/or pazopanib-induced remitting seronegative symmetrical synovitis with pitting edema can be among the rare rheumatic immune-related adverse events that clinicians may encounter as the immune check point inhibitors and anti-VEGF use increases. Corticosteroid therapy can relieve symptoms and cessation of therapy may not be necessary.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Edema/inducido químicamente , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/efectos adversos , Sulfonamidas/efectos adversos , Sinovitis/inducido químicamente , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Células Renales/diagnóstico , Quimioterapia Combinada , Edema/diagnóstico , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación , Sinovitis/diagnóstico
16.
Small ; 15(24): e1900873, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31058444

RESUMEN

Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load-dependent recruitment. Scaffolds with precisely-defined serpentine architectures reproduce the J-shaped strain stiffening, anisotropic and viscoelastic behavior of native heart valve leaflets, as demonstrated by quasistatic and dynamic mechanical characterization. They also support the growth of human vascular smooth muscle cells seeded both directly or encapsulated in fibrin, and promote the deposition of valvular extracellular matrix components. Finally, proof-of-principle MEW trileaflet valves display excellent acute hydrodynamic performance under aortic physiological conditions in a custom-made flow loop. The convergence of MEW and a biomimetic design approach enables a new paradigm for the manufacturing of scaffolds with highly controlled microarchitectures, biocompatibility, and stringent nonlinear and anisotropic mechanical properties required for HVTE.


Asunto(s)
Biomimética/instrumentación , Galvanoplastia/métodos , Válvulas Cardíacas/citología , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido/química , Fenómenos Biomecánicos , Biomimética/métodos , Prótesis Vascular , Células Cultivadas , Regeneración Tisular Dirigida/instrumentación , Regeneración Tisular Dirigida/métodos , Enfermedades de las Válvulas Cardíacas/patología , Enfermedades de las Válvulas Cardíacas/terapia , Humanos , Recién Nacido , Ensayo de Materiales , Miocitos del Músculo Liso/citología , Polímeros/química , Ingeniería de Tejidos/instrumentación , Ingeniería de Tejidos/métodos , Cordón Umbilical/citología
18.
Biofabrication ; 11(3): 035028, 2019 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-30645987

RESUMEN

We present a study on ternary nanocomposites consisting of medical grade poly(ε-caprolactone) (mPCL) matrix, hydroxyapatite nanopowder (nHA) and compatibilized magnesium fluoride nanoparticle (cMgF2) fillers. MgF2 nanoparticles were compatibilized by following a design approach based on the material interfaces of natural bone. MgF2-specific peptide-poly(ethylene glycol) conjugates were synthesized and used as surface modifiers for MgF2 nanoparticles similarly to the non-collagenous proteins (NPC) of bone which compatibilize hydroxyapatite nanocrystallites. Different compositions of mPCL/nHA/cMgF2 composites were blended together and processed into three dimensional (3D) scaffolds using solvent-free techniques including cryomilling and melt extrusion-based additive manufacturing. The use of two different inorganic fillers in mPCL resulted in nanocomposite materials with enhanced mechanical and biological properties. In particular, cMgF2 nanoparticles were found to be the primary constitent leading to the significant improvements in the mechanical properties of these composites. The scaffolds of the ternary nanocomposites provided the best in vitro performance in terms of osteogenic differentiation and stimulated mineralization. In summary, we demonstrated that the concept of bioinspired interface engineering facilitates the development of homogeneous ternary nanocomposites with increased processability in additive biomanufacturing. Additionally, the concept leads to scaffolds exhibiting enhanced mechanical and biological properties. Overall, these multicomponent nano-interfaced building blocks add a new group of advanced functional materials with tunable mechanical properties, degradation and bioactivity.


Asunto(s)
Materiales Biocompatibles/farmacología , Nanocompuestos/química , Péptidos/química , Polímeros/química , Impresión Tridimensional , Materiales Biomiméticos/química , Diferenciación Celular , Proliferación Celular , Supervivencia Celular , Durapatita/química , Fluoruros/química , Humanos , Compuestos de Magnesio/química , Células Madre Mesenquimatosas/citología , Nanocompuestos/ultraestructura , Poliésteres/química , Andamios del Tejido/química , Microtomografía por Rayos X
19.
Biofabrication ; 11(2): 025004, 2019 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-30616231

RESUMEN

Melt electrowriting (MEW) combines the fundamental principles of electrospinning, a fibre forming technology, and 3D printing. The process, however, is highly complex and the quality of the fabricated structures strongly depends on the interplay of key printing parameter settings including processing temperature, applied voltage, collection speed, and applied pressure. These parameters act in unison, comprising the principal forces on the electrified jet: pushing the viscous polymer out of the nozzle and mechanically and electrostatically dragging it for deposition towards the collector. Although previous studies interpreted the underlying mechanism of electrospinning with polymer melts in a direct writing mode, contemporary devices used in laboratory environments lack the capability to collect large data reproducibly. Yet, a validated large data set is a condition sine qua non to design an in-process control system which allows to computer control the complexity of the MEW process. For this reason, we engineered an advanced automated MEW system with monitoring capabilities to specifically generate large, reproducible data volumes which allows the interpretation of complex process parameters. Additionally, the design of an innovative real-time MEW monitoring system identifies the main effects of the system parameters on the geometry of the fibre flight path. This enables, for the first time, the establishment of a comprehensive correlation between the input parameters and the geometry of a MEW jet. The study verifies the most stable process parameters for the highly reproducible fabrication of a medical-grade poly(ε-caprolactone) fibres and demonstrates how Printomics can be performed for the high throughput analysis of processing parameters for MEW.


Asunto(s)
Técnicas Electroquímicas/métodos , Impresión Tridimensional , Aceleración , Electricidad , Temperatura , Viscosidad
20.
J Mater Chem B ; 7(10): 1761-1772, 2019 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-32254918

RESUMEN

Gelatin methacryloyl (GelMA) hydrogels are a mechanically and biochemically tuneable biomaterial, facilitating chondrocyte culture for tissue engineering applications. However, a lack of characterisation and standardisation of fabrication methodologies for GelMA restricts its utilisation in surgical interventions for articular cartilage repair. The purpose of this study was to determine the effects of gelatin source and photoinitiator type on the redifferentiation capacity of monolayer-expanded human articular chondrocytes encapsulated in GelMA/hyaluronic acid methacrylate (HAMA) hydrogels. Chondrocyte-laden hydrogels reinforced with multiphasic melt-electrowritten (MEW) medical grade polycaprolactone (mPCL) microfibre scaffolds were prepared using bovine (B) or porcine-derived (P) GelMA, and photocrosslinked with either lithium acylphosphinate (LAP) and visible light (405 nm) or Irgacure 2959 (IC) and UV light (365 nm). Bulk physical properties, cell viability and biochemical features of hydrogel constructs were measured at day 1 and day 28 of chondrogenic cell culture. The compressive moduli of all groups increased after 28 days of cell culture, with B-IC displaying similar compressive strength to that of native articular cartilage (∼1.5 MPa). Compressive moduli correlated with an increase in total glycosaminoglycan (GAG) content for each group. Gene expression analysis revealed upregulation of chondrogenic marker genes in IC-crosslinked groups, whilst dedifferentiation gene markers were upregulated in LAP-crosslinked groups. mPCL reinforcement correlated with increased accumulation of collagen I and II in B-IC, B-LAP and P-IC groups compared to non-reinforced hydrogels. A reduction in cell viability was noted in all samples at day 28, potentially due to the generation of free radicals during photocrosslinking or cytotoxicity of the photoinitiators. In summary, hydrogel constructs prepared with bovine-derived GelMA and photocrosslinked with Irgacure 2959 and 365 nm light displayed properties most similar to native articular cartilage after 28 days of cell culture. The differences in biological response between investigated construct types emphasises the necessity to characterise and standardise biomaterials before translating in vitro tissue engineering research to preclinical applications for articular cartilage injuries.


Asunto(s)
Condrocitos/química , Condrogénesis/efectos de los fármacos , Gelatina/química , Ingeniería de Tejidos/métodos , Humanos
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