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1.
Biomacromolecules ; 20(7): 2494-2505, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31083976

RESUMO

After more than 22 years of research challenges and innovation, the heart valve tissue engineering paradigm still attracts attention as an approach to overcome limitations which exist with clinically utilized mechanical or bioprosthetic heart valves. Despite encouraging results, delayed translation can be attributed to limited knowledge on the concurrent mechanisms of biomaterial degradation in vivo, host inflammatory response, cell recruitment, and de novo tissue elaboration. This study aimed to reduce this gap by evaluating three alternative levels at which lability could be incorporated into candidate polyurethane materials electroprocessed into a valve scaffold. Specifically, polyester and polycarbonate labile soft segment diols were reacted into thermoplastic elastomeric polyurethane ureas that formed scaffolds where (1) a single polyurethane containing both of the two diols in the polymer backbone was synthesized and processed, (2) two polyurethanes were physically blended, one with exclusively polycarbonate and one with exclusively polyester diols, followed by processing of the blend, and (3) the two polyurethane types were concurrently processed to form individual fiber populations in a valve scaffold. The resulting valve scaffolds were characterized in terms of their mechanics before and after exposure to varying periods of pulsatile flow in an enzymatic (lipase) buffer solution. The results showed that valve scaffolds made from the first type of polymer and processing combination experienced more extensive degradation. This approach, although demonstrated with polyurethane scaffolds, can generally be translated to investigate biomaterial approaches where labile elements are introduced at different structural levels to alter degradation properties while largely preserving the overall chemical composition and initial mechanical behavior.


Assuntos
Materiais Biocompatíveis/química , Próteses Valvulares Cardíacas , Teste de Materiais , Poliésteres/química , Poliuretanos/química , Animais , Suínos
2.
Soft Matter ; 14(42): 8483-8495, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30357253

RESUMO

Physical cues are decisive factors in extracellular matrix (ECM) formation and elaboration. Their transduction across scale lengths is an inherently symbiotic phenomenon that while influencing ECM fate is also mediated by the ECM structure itself. This study investigates the possibility of enhancing ECM elaboration by topological cues that, while not modifying the substrate macro scale mechanics, can affect the meso-scale strain range acting on cells incorporated within the scaffold. Vascular smooth muscle cell micro-integrated, electrospun scaffolds were fabricated with comparable macroscopic biaxial mechanical response, but different meso-scale topology. Seeded scaffolds were conditioned on a stretch bioreactor and exposed to large strain deformations. Samples were processed to evaluate ECM quantity and quality via: biochemical assay, qualitative and quantitative histological assessment and multi-photon analysis. Experimental evaluation was coupled to a numerical model that elucidated the relationship between the scaffold micro-architecture and the strain acting on the cells. Results showed an higher amount of ECM formation for the scaffold type characterized by lowest fiber intersection density. The numerical model simulations associated this result with the differences found for the change in cell nuclear aspect ratio and showed that given comparable macro scale mechanics, a difference in material topology created significant differences in cell-scaffold meso-scale deformations. These findings reaffirmed the role of cell shape in ECM formation and introduced a novel notion for the engineering of cardiac tissue where biomaterial structure can be designed to both mimick the organ level mechanics of a specific tissue of interest and elicit a desirable cellular response.

3.
Cureus ; 15(1): e34226, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36852355

RESUMO

Failure to thrive in the setting of profound hypotonia and multiple electrolyte derangements is a challenging constellation of findings that offers a broad differential diagnosis for providers to consider. Initial management should focus on the stabilization of the patient and correction of potential life-threatening electrolyte derangements. Once completed, the diagnosis should be sought, and in this case, many were considered and ultimately ruled out with thorough history and physical examination. Laboratory abnormalities revealed the final diagnosis of pseudohypoaldosteronism and connected the case. With proper treatment, our patient had a resolution of laboratory anomalies along with improved growth and tone.

4.
J Pediatr Urol ; 19(5): 582.e1-582.e5, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37353360

RESUMO

INTRODUCTION: Double-diaper technique with an open-drainage catheter is a common practice after hypospadias repair. However, double-diapering may increase the burden of postoperative care and has not been compared to single-diapering with an open-drainage catheter. OBJECTIVES: This study investigates whether the single-diaper technique is associated with inferior surgical outcomes compared to the double-diaper technique. MATERIALS AND METHODS: A single surgeon database was retrospectively reviewed for patients who underwent hypospadias repair between 2013 and 2021. Patients who were lost to follow-up and those in whom the type of diaper care (single- or double-diaper) was not documented were excluded. Patients in the single-diaper technique received the same type of dressing and discharge instructions, as those in the double-diaper group, except for leaving the catheter freely draining into a single-diaper. Short-term complications including surgical site infection (SSI), urinary tract infection (UTI) and wound dehiscence, were the primary outcome; whereas the long-term urethroplasty complications (urethrocutaneous fistula and meatal stenosis) were secondary outcomes. Outcomes were analyzed according to the type of diaper care. RESULTS: Among 323 patients reviewed, 219 patients met the inclusion criteria (72 patients in the double-diaper and 147 in the single-diaper group). Both study groups were similar regarding patient demographics, hypospadias characteristics and surgical technique. Looking at the primary outcomes, there was no statistically significant difference in SSI, UTI or wound dehiscence. For the secondary outcomes, the incidence of meatal stenosis (8.3 vs. 1.4%, p = 0.044), and fistula formation (15.3% vs 5.4%, p = 0.037) was significantly higher in the double-diaper than the single-diaper group, respectively (Table 2). CONCLUSION: Single-diaper technique following hypospadias repair is not associated with increased risk of complications compared to double-diaper technique.


Assuntos
Fístula , Hipospadia , Estreitamento Uretral , Masculino , Humanos , Lactente , Hipospadia/cirurgia , Hipospadia/etiologia , Estudos Retrospectivos , Constrição Patológica/etiologia , Uretra/cirurgia , Infecção da Ferida Cirúrgica , Estreitamento Uretral/cirurgia , Fístula/etiologia , Fístula/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
5.
Urol Case Rep ; 47: 102355, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36866338

RESUMO

Diffuse large B-cell lymphoma (DLBCL) of the genitourinary tract is a rare diagnosis. A 66-year-old male with a history of multiple myeloma and prostate cancer presented with gross hematuria and concern for urinary clot retention. Imaging demonstrated an incidental mass in the left kidney and urinary bladder. Resection of the urinary bladder tumor and biopsy of the kidney revealed Epstein-Barr Virus positive DLBCL. Significant lymphadenopathy was found during staging, and this lymphoma was classified as stage IV. The patient was referred to medical oncology, initiated on chemotherapy, and scheduled for follow up with urology for the renal mass.

6.
Pediatr Pulmonol ; 57(10): 2568-2570, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35856236

RESUMO

Pneumothorax as a sequela of vaping is a relatively recent complication being described in the literature. Smoking has classically been associated with an increased risk of pneumothorax, and emerging evidence is showing that electronic cigarettes (e-cigarettes) likely carry some of the same risks. Since e-cigarettes increased in popularity, especially among the adolescent population, there has been a reported increased incidence of lung injury, including pneumothorax. We present a case of a 15-year-old female with a history of e-cigarette use admitted for recurrent pneumothorax with failure to re-expand requiring surgical intervention.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Pneumotórax , Abandono do Hábito de Fumar , Vaping , Adolescente , Feminino , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/terapia , Fumar Tabaco , Vaping/efeitos adversos , Vaping/epidemiologia
7.
Cureus ; 14(5): e24982, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35719761

RESUMO

Acute ischemic stroke (AIS) is a significant source of morbidity and mortality and is one of the top causes of death in the United States. Of these patients, most are elderly individuals, compared to a limited proportion of cases seen in pediatrics. AIS is classically associated with age-dependent atherosclerotic disease processes secondary to comorbidities such as diabetes and hypertension. When considering the pediatric population, stroke is far less common and often requires workup of other underlying etiologies that create a hypercoagulable state. Here we present a case of an eight-year-old male with a left middle cerebral artery (MCA) ischemic stroke in the setting of increased factor VIII activity and SARS-CoV-2 antibodies.

8.
J Mech Behav Biomed Mater ; 128: 105126, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35180648

RESUMO

Effective cardiovascular tissue surrogates require high control of scaffold structural and mechanical features to match native tissue properties, which are dependent on tissue-specific mechanics, function heterogenicity, and morphology. Bridging scaffold processing variables with native tissue properties is recognized as a priority for advancing biomechanical performance of biomedical materials and, when translated to the clinical practice, their efficacy. Accordingly, this study selected electrospinning on a rotating cylindrical target as an apparatus of broad application and mapped the relationship between key processing variables and scaffold mechanics and structure. This information was combined with mechanical anisotropy ranges of interest for the three main categories of tissue surrogated in cardiovascular tissue engineering: heart valve leaflets, ventricle wall, and large diameter blood vessels. Specifically, three processing variables have been considered: the rotational velocity and the rastering velocity of the mandrel and the dry (single nozzle - polymer only) vs wet (double nozzle - polymer plus phosphate buffer saline solution) fabrication configuration. While the dry configuration is generally utilized to obtain micro-fiber based polymeric mats, the wet fabrication is representative of processing conditions utilized to incorporate cells, growth factors, or micro-particles within the fibrous scaffold matrix. Dry and wet processed electrospun mats were fabricated with tangential and rastering velocities within the 0.3-9.0 m/s and 0.16-8 cm/s range respectively. Biaxial mechanics, fiber network, and pore micro-architectures were measured for each combination of velocities and for each fabrication modality (dry and wet). Results allowed identification of the precise combination of rotational and rastering velocities, for both dry and wet conditions, that is able to recapitulate the native cardiovascular tissue anisotropy ratio. By adopting a simple and broadly utilized electrospinning layout, this study is meant to provide a repeatable and easy to access methodology to improve biomimicry of the in plane-mechanics of heart valve leaflets, ventricular wall, and large diameter blood vessels.


Assuntos
Sistema Cardiovascular , Poliuretanos , Materiais Biocompatíveis/química , Poliésteres/química , Poliuretanos/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química
9.
JACC Basic Transl Sci ; 6(5): 447-463, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34095634

RESUMO

A biohybrid patch without cellular components was implanted over large infarcted areas in severely dilated hearts. Nonpatched animals were assigned to control or losartan therapy. Patch-implanted animals responded with better morphological and functional echocardiographic endpoints, which were more evident in a subgroup of animals with very low pre-treatment ejection fraction (<35%). Patched animals also had smaller infarcts than both nonpatched groups. This simple approach could hold promise for clinical translation and be applied using minimally invasive procedures over the epicardium in a large set of patients to induce better ventricular remodeling, especially among those who are especially frail.

10.
Acta Biomater ; 121: 275-287, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33129986

RESUMO

Traditional Anterior Cruciate Ligament (ACL) reconstruction is commonly performed using an allograft or autograft and possesses limitations such as donor site morbidity, decreased range of motion, and potential infection. However, a biodegradable synthetic graft could greatly assist in the prevention of such restrictions after ACL reconstruction. In this study, artificial grafts were generated using "wet" and "dry" electrospinning processes with a biodegradable elastomer, poly (ester urethane) urea (PEUU), and were evaluated in vitro and in vivo in a rat model. Four groups were established: (1) Wet PEUU artificial ligament, (2) Dry PEUU artificial ligament, (3) Dry polycaprolactone artificial ligament (PCL), and (4) autologous flexor digitorum longus tendon graft. Eight weeks after surgery, the in vivo tensile strength of wet PEUU ligaments had significantly increased compared to the other synthetic ligaments. These results aligned with increased infiltration of host cells and decreased inflammation within the wet PEUU grafts. In contrast, very little cellular infiltration was observed in PCL and dry PEUU grafts. Micro-computed tomography analysis performed at 4 and 8 weeks postoperatively revealed significantly smaller bone tunnels in the tendon autograft and wet PEUU groups. The Wet PEUU grafts served as an adequate functioning material and allowed for the creation of tissues that closely resembled the ACL.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Animais , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Ratos , Tendões/cirurgia , Transplante Autólogo , Microtomografia por Raio-X
11.
J Cardiovasc Transl Res ; 13(5): 796-805, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040766

RESUMO

Degradable heart valves based on in situ tissue regeneration have been proposed as potentially durable and non-thrombogenic prosthetic alternatives. We evaluated the acute in vivo function, microstructure, mechanics, and thromboresistance of a stentless biodegradable tissue-engineered heart valve (TEHV) in the tricuspid position. Biomimetic stentless tricuspid valves were fabricated with poly(carbonate urethane)urea (PCUU) by double-component deposition (DCD) processing to mimic native valve mechanics and geometry. Five swine then underwent 24-h TEHV implantation in the tricuspid position. Echocardiography demonstrated good leaflet motion and no prolapse and trace to mild regurgitation in all but one animal. Histology revealed patches of proteinaceous deposits with no cellular uptake. SEM demonstrated retained scaffold microarchitecture with proteinaceous deposits but no platelet aggregation or thrombosis. Explanted PCUU leaflet thickness and mechanical anisotropy were comparable with native tricuspid leaflets. Bioinspired, elastomeric, stentless TEHVs fabricated by DCD were readily implantable and demonstrated good acute function in the tricuspid position.


Assuntos
Elastômeros/química , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Poliuretanos/química , Valva Tricúspide/cirurgia , Animais , Implante de Prótese de Valva Cardíaca/efeitos adversos , Hemodinâmica , Teste de Materiais , Modelos Animais , Desenho de Prótese , Sus scrofa , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/fisiopatologia , Valva Tricúspide/ultraestrutura , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/fisiopatologia
12.
Front Bioeng Biotechnol ; 8: 597847, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195168

RESUMO

Vascular tissue engineering is a field of regenerative medicine that restores tissue function to defective sections of the vascular network by bypass or replacement with a tubular, engineered graft. The tissue engineered vascular graft (TEVG) is comprised of a biodegradable scaffold, often combined with cells to prevent acute thrombosis and initiate scaffold remodeling. Cells are most effectively incorporated into scaffolds using bulk seeding techniques. While our group has been successful in uniform, rapid, bulk cell seeding of scaffolds for TEVG testing in small animals using our well-validated rotational vacuum technology, this approach was not directly translatable to large scaffolds, such as those required for large animal testing or human implants. The objective of this study was to develop and validate a semi-automated cell seeding device that allows for uniform, rapid, bulk seeding of large scaffolds for the fabrication of TEVGs appropriately sized for testing in large animals and eventual translation to humans. Validation of our device revealed successful seeding of cells throughout the length of our tubular scaffolds with homogenous longitudinal and circumferential cell distribution. To demonstrate the utility of this device, we implanted a cell seeded scaffold as a carotid interposition graft in a sheep model for 10 weeks. Graft remodeling was demonstrated upon explant analysis using histological staining and mechanical characterization. We conclude from this work that our semi-automated, rotational vacuum seeding device can successfully seed porous tubular scaffolds suitable for implantation in large animals and provides a platform that can be readily adapted for eventual human use.

13.
J Thorac Cardiovasc Surg ; 157(1): 176-183, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30274840

RESUMO

OBJECTIVES: The present study compared physical, mechanical, and biologic characteristics of 4 clinically available surgical sealants for cardiovascular repair. METHODS: BioGlue (Cryolife Inc, Kennesaw, Ga), PreveLeak (Mallinckrodt Pharmaceuticals, St Louis, Mo), Tridyne VS (BD, Franklin Lakes, NJ), and Coseal (Baxter Healthcare Corporation, Westlake Village, Calif) were compared for the following properties: hydrated swelling, cytocompatibility, burst strength, biaxial stretching (elasticity), and in vitro degradation. RESULTS: Sealants showed a wide range of swelling upon hydration. By gravimetric and volumetric measurement, swelling was greatest for Coseal followed by Tridyne VS, BioGlue, and PreveLeak. Tridyne VS was the most cytocompatible based on Alamar Blue assay results, supporting 85% cell survival compared with 36% to 39% survival with the other sealants. All sealants withstood pressure above mean arterial pressure (70-110 mm Hg) and physiologic systolic blood pressure (90-140 mm Hg) in an ex vivo arterial flow burst model; lowest peak pressure at failure was PreveLeak at 235 ± 48 mm Hg, and highest peak pressure at failure was BioGlue at 596 ± 72 mm Hg. Biaxial tensile testing showed no differences in elasticity between ex vivo porcine aorta and carotid arteries and Tridyne VS or Coseal, and BioGlue and PreveLeak were significantly stiffer. In vitro degradation time for Coseal was 6 days and 21 days for Tridyne VS. No degradation was observed in BioGlue or PreveLeak for 30 days. CONCLUSIONS: Although all sealants withstood supraphysiologic arterial pressure, there were differences in characteristics that may be important in clinical outcome. Coseal degradation time was short compared with other sealants, whereas BioGlue and PreveLeak showed a significant compliance mismatch with native porcine carotid artery. Tridyne VS was significantly more cytocompatible than the other 3 sealants.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Adesivos Teciduais/uso terapêutico , Animais , Aorta/cirurgia , Procedimentos Cirúrgicos Cardiovasculares , Artérias Carótidas/cirurgia , Elasticidade , Humanos , Fenômenos Mecânicos , Polietilenoglicóis/uso terapêutico , Pressão , Proteínas/uso terapêutico , Suínos , Resistência à Tração
14.
J Thorac Cardiovasc Surg ; 157(5): 1809-1816, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30578064

RESUMO

OBJECTIVE: Ideal heart valve solutions aim to provide thrombosis-free durability. A scaffold-based polycarbonate urethane urea tissue-engineered heart valve designed to mimic native valve microstructure and function was used. This study examined the acute in vivo function of a stented tissue-engineered heart valve in a porcine model. METHODS: Trileaflet valves were fabricated by electrospinning polycarbonate urethane urea using double component fiber deposition. The tissue-engineered heart valve was mounted on an AZ31 magnesium alloy biodegradable stent frame. Five 80-kg Yorkshire pigs underwent open tissue-engineered heart valve implantation on cardiopulmonary bypass in the pulmonary position. Tissue-engineered heart valve function was echocardiographically evaluated immediately postimplant and at planned study end points at 1, 4, 8, and 12 hours. Explanted valves underwent biaxial mechanical testing and scanning electron microscopy for ultrastructural analysis and thrombosis detection. RESULTS: All 5 animals underwent successful valve implantation. All were weaned from cardiopulmonary bypass, closed, and recovered until harvest study end point except 1 animal that was found to have congenital tricuspid valve dysplasia and that was euthanized postimplant. All 5 cases revealed postcardiopulmonary bypass normal leaflet function, no regurgitation, and an average peak velocity of 2 m/s, unchanged at end point. All tissue-engineered heart valve leaflets retained microstructural architecture with no platelet activation or thrombosis by scanning electron microscopy. There was microscopic evidence of fibrin deposition on 2 of 5 stent frames, not on the tissue-engineered heart valve. Biaxial stress examination revealed retained postimplant mechanics of tissue-engineered heart valve fibers without functional or ultrastructural degradation. CONCLUSIONS: A biodegradable elastomeric heart valve scaffold for in situ tissue-engineered leaflet replacement is acutely functional and devoid of leaflet microthrombosis.


Assuntos
Implantes Absorvíveis , Ligas/química , Elastômeros/química , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Valva Pulmonar/cirurgia , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Implante de Prótese de Valva Cardíaca/efeitos adversos , Teste de Materiais , Modelos Animais , Desenho de Prótese , Falha de Prótese , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/ultraestrutura , Estresse Mecânico , Sus scrofa , Trombose/etiologia , Fatores de Tempo
15.
Biomaterials ; 217: 119289, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31254935

RESUMO

Intramyocardial hydrogel injection is an innovative and promising treatment for myocardial infarction (MI) and has recently entered clinical trials. By providing mechanical support to the ventricular wall, hydrogel injectate may act to preserve cardiac function and slow the remodeling process that leads to heart failure. However, improved outcomes will likely depend on the use of hydrogels specifically designed for this unique application, and better understanding of the mechanisms affected by the intervention. In this work, we present the first large animal study achieving functional and geometrical improvements in treating MI using a relatively stiff, fully synthetic hydrogel designed for intramyocardial injection. In addition, the renin-angiotensin system coincided with the mechanical effects of hydrogel injection and attenuated left ventricular remodeling, even after significant hydrogel degradation had occurred in vivo. These results may inspire further optimization of hydrogel materials used in intramyocardial hydrogel injection therapy and a better description of physiologic pathways affected by its implementation to facilitate successful clinical translation.


Assuntos
Hidrogéis/administração & dosagem , Hidrogéis/farmacologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Feminino , Testes de Função Cardíaca , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Injeções , Macrófagos/efeitos dos fármacos , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Neovascularização Fisiológica/efeitos dos fármacos , Ratos Endogâmicos Lew , Suínos
17.
J Biomed Mater Res B Appl Biomater ; 106(2): 659-671, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28296198

RESUMO

In pediatric cardiovascular surgery, there is a significant need for vascular prostheses that have the potential to grow with the patient following implantation. Current clinical options consist of nonexpanding conduits, requiring repeat surgeries as the patient outgrows the device. To address this issue, PECA Labs has developed a novel ePTFE vascular conduit with the capability of being radially expanded via balloon catheterization. In the described study, a systematic characterization and comparison of two proprietary ePTFE expandable conduits was conducted. Conduit sizes of 8 and 16 mm inner diameters for both conduits were evaluated before and after expansion with a 26 mm balloon. Comprehensive mechanical testing was completed, including quantification of circumferential, and longitudinal tensile strength, suture retention strength, burst strength, water entry pressure, dynamic compliance, and kink radius. Scanning electron microscopy was used to investigate the microstructural properties. Automated extraction of the fiber architectural features for each scanning electron micrograph was achieved with an algorithm for each conduit before and after expansion. Results showed that both conduits were able to expand significantly, to as much as 2.5× their original inner diameter. All mechanical properties were within clinically acceptable values following expansion. Analysis of the microstructure properties of the conduits revealed that the circumferential main angle of orientation, orientation index, and spatial periodicity did not significantly change following expansion, whereas the node area fraction decreased post expansion. Successful proof-of-concept of this novel product represents a critical step toward clinical translation and provides hope for newborns and growing children with congenital heart disease. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 659-671, 2018.


Assuntos
Prótese Vascular , Procedimentos Cirúrgicos Cardiovasculares , Cardiopatias/congênito , Cardiopatias/cirurgia , Politetrafluoretileno/química , Desenho de Prótese , Doenças Vasculares/cirurgia , Cateterismo Cardíaco , Cateteres Cardíacos , Criança , Humanos , Recém-Nascido , Retenção da Prótese , Resistência à Tração , Doenças Vasculares/congênito
18.
Tissue Eng Part A ; 24(11-12): 889-904, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29187125

RESUMO

Ventral hernia is often addressed surgically by the placement of prosthetic materials, either synthetic or from allogeneic and xenogeneic biologic sources. Despite advances in surgical approaches and device design, a number of postsurgical limitations remain, including hernia recurrence, mesh encapsulation, and reduced vascularity of the implanted volume. The in situ controlled release of angiogenic factors from a scaffold facilitating abdominal wall repair might address some of these issues associated with suboptimal tissue reconstruction. Furthermore, a biocomposite material that combines the favorable mechanical properties achievable with synthetic materials and the bioactivity associated with xenogeneic tissue sources would be desirable. In this report, an abdominal wall repair scaffold has been designed based on a microfibrous, elastomeric poly(ester carbonate)urethane urea matrix integrated with a hydrogel derived from decellularized porcine dermis (extracellular matrix [ECM] gel) and poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nitro-oleic acid (NO2-OA). NO2-OA is an electrophilic fatty acid nitro-alkene derivative that, under hypoxic conditions, induces angiogenesis. This scaffold was utilized to repair a rat abdominal wall partial thickness defect, hypothesizing that the nitro-fatty acid release would facilitate increased angiogenesis at the 8-week endpoint. The quantification of neovascularization was conducted by novel methodologies to assess vessel morphology and spatial distribution. The repaired abdominal wall defects were evaluated by histopathologic methods, including quantification of the foreign body response and cellular ingrowth. The results showed that NO2-OA release was associated with significantly improved regional angiogenesis. The combined biohybrid scaffold and NO2-OA-controlled release strategy also reduced scaffold encapsulation, increased wall thickness, and enhanced cellular infiltration. More broadly, the three components of the composite scaffold design (ECM gel, polymeric fibers, and PLGA microparticles) enable the tuning of performance characteristics, including scaffold bioactivity, degradation, mechanics, and drug release profile, all decisive factors to better address current limitations in abdominal wall repair or other soft tissue augmentation procedures.


Assuntos
Parede Abdominal , Ácido Oleico/uso terapêutico , Animais , Materiais Biocompatíveis , Matriz Extracelular/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Ratos
19.
J Tissue Eng Regen Med ; 12(6): 1374-1388, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29677404

RESUMO

The challenge of developing scaffolds to reconstruct critical-sized calvarial defects without the addition of high levels of exogenous growth factor remains relevant. Both osteogenic regenerative efficacy and suitable mechanical properties for the temporary scaffold system are of importance. In this study, a Mg alloy mesh reinforced polymer/demineralized bone matrix (DBM) hybrid scaffold was designed where the hybrid scaffold was fabricated by a concurrent electrospinning/electrospraying of poly(lactic-co-glycolic acid) (PLGA) polymer and DBM suspended in hyaluronic acid (HA). The Mg alloy mesh significantly increased the flexural strength and modulus of PLGA/DBM hybrid scaffold. In vitro results demonstrated that the Mg alloy mesh reinforced PLGA/DBM hybrid scaffold (Mg-PLGA@HA&DBM) exhibited a stronger ability to promote the proliferation of bone marrow stem cells (BMSCs) and induce BMSC osteogenic differentiation compared with control scaffolding materials lacking critical components. In vivo osteogenesis studies were performed in a rat critical-sized calvarial defect model and incorporated a variety of histological stains and immunohistochemical staining of osteocalcin. At 12 weeks, the rat model data showed that the degree of bone repair for the Mg-PLGA@HA&DBM scaffold was significantly greater than for those scaffolds lacking one or more of the principal components. Although complete defect filling was not achieved, the improved mechanical properties, promotion of BMSC proliferation and induction of BMSC osteogenic differentiation, and improved promotion of bone repair in the rat critical-sized calvarial defect model make Mg alloy mesh reinforced PLGA/DBM hybrid scaffold an attractive option for the repair of critical-sized bone defects where the addition of exogenous isolated growth factors is not employed.


Assuntos
Ligas/farmacologia , Matriz Extracelular/química , Magnésio/farmacologia , Crânio/patologia , Alicerces Teciduais/química , Fosfatase Alcalina/metabolismo , Animais , Matriz Óssea/química , Cálcio/metabolismo , Feminino , Osteogênese/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Ratos Sprague-Dawley
20.
J Thorac Cardiovasc Surg ; 156(5): 1814-1822.e3, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30057192

RESUMO

OBJECTIVE: Tissue-engineered vascular grafts containing adipose-derived mesenchymal stem cells offer an alternative to small-diameter vascular grafts currently used in cardiac and lower-extremity revascularization procedures. Adipose-derived, mesenchymal stem cell-infused, tissue-engineered vascular grafts have been shown to promote remodeling and vascular homeostasis in vivo and offer a possible treatment solution for those with cardiovascular disease. Unfortunately, the time needed to cultivate adipose-derived mesenchymal stem cells remains a large hurdle for tissue-engineered vascular grafts as a treatment option. The purpose of this study was to determine if stromal vascular fraction (known to contain progenitor cells) seeded tissue-engineered vascular grafts would remain patent in vivo and remodel, allowing for a "same-day" process for tissue-engineered vascular graft fabrication and implantation. METHODS: Stromal vascular fraction, obtained from adult human adipose tissue, was seeded within 4 hours after acquisition from the patient onto poly(ester urethane)urea bilayered scaffolds using a customized rotational vacuum seeding device. Constructs were then surgically implanted as abdominal aortic interposition grafts in Lewis rats. RESULTS: Findings revealed patency in 5 of 7 implanted scaffolds at 8 weeks, along with neotissue formation and remodeling occurring in patent tissue-engineered vascular grafts. Patency was documented using angiography and gross inspection, and remodeling and vascular components were detected using immunofluorescent chemistry. CONCLUSIONS: A "same-day" cell-seeded, tissue-engineered vascular graft can remain patent after implantation in vivo, with neotissue formation and remodeling occurring by 8 weeks.


Assuntos
Tecido Adiposo/citologia , Aorta Abdominal/cirurgia , Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Transplante de Células-Tronco/instrumentação , Células Estromais/fisiologia , Células Estromais/transplante , Engenharia Tecidual/métodos , Alicerces Teciduais , Adulto , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aorta Abdominal/fisiopatologia , Biomarcadores/metabolismo , Células Cultivadas , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Neointima , Fenótipo , Desenho de Prótese , Ratos Endogâmicos Lew , Células Estromais/metabolismo , Fatores de Tempo , Transplante Heterólogo , Grau de Desobstrução Vascular , Remodelação Vascular , Fluxo de Trabalho
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