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1.
J Robot Surg ; 18(1): 100, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38413496

RESUMO

Cystectomy is the gold standard treatment for muscle invasive bladder cancer. Robotic cystectomy has become increasingly popular owing to quicker post- operative recovery, less blood loss and less post-operative pain. Urinary diversion is increasingly being performed with an intracorporeal technique. Uretero-enteric strictures (UES) cause significant morbidity for patients. UES for open cystectomy is 3-10%, but the range is much wider (0-25%) for robotic surgery. We aim to perform systematic review for studies comparing all 3 techniques, to assess for ureteric stricture rates. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (Page et al. in BMJ 29, 2021). PubMed, Scopus and Embase databases were searched for the period January 2003 to June 2023 inclusive for relevant publications.The primary outcome was to identify ureteric stricture rates for studies comparing open cystectomy and urinary diversion, robotic cystectomy with extracorporeal urinary diversion (ECUD) and robotic cystectomy with intracorporeal urinary diversion (ICUD). Three studies were identified and included 2185 patients in total. The open operation had the lowest stricture rate (9.6%), compared to ECUD (12.4%) and ICUD (15%). ICUD had the longest time to stricture (7.55 months), ECUD (4.85 months) and the open operation (4.75 months). Open operation had the shortest operating time. The Bricker anastomoses was the most popular technique. Open surgery has the lowest rates of UES compared to both robotic operations. There is a learning curve involved with performing robotic cystectomy and urinary diversion, this may need to be considered to decide whether the technique is comparable with open cystectomy UES rates. Further research, including Randomised Control Trials (RCT), needs to be undertaken to determine the best surgical option for patients to minimise risks of UES.


Assuntos
Procedimentos Cirúrgicos Robóticos , Obstrução Ureteral , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Cistectomia/efeitos adversos , Cistectomia/métodos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Derivação Urinária/efeitos adversos , Derivação Urinária/métodos , Neoplasias da Bexiga Urinária/cirurgia , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgia , Estudos Retrospectivos
3.
Nat Commun ; 15(1): 1142, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326301

RESUMO

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized ß-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions. The self-assembled fibrils maintain enhanced binding to viral protein complexes and retain high resilience to viral mutations. This method is experimentally and computationally tested using short peptides that specifically bind to Spike proteins of SARS-CoV-2. This platform is efficacious, inexpensive, and stable with excellent tolerability.


Assuntos
COVID-19 , Humanos , Peptídeos/química , SARS-CoV-2/metabolismo , Antivirais/farmacologia , Proteínas Virais , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
ACS Appl Mater Interfaces ; 16(1): 364-375, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38145951

RESUMO

Growth factor (GF) mimicry involves recapitulating the signaling of larger molecules or cells. Although GF mimicry holds considerable promise in tissue engineering and drug design applications, difficulties in targeting the signaling molecule to the site of delivery and dissociation of mimicking peptides from their target receptors continue to limit its clinical application. To address these challenges, we utilized a self-assembling peptide (SAP) platform to generate synthetic insulin-like growth factor (IGF)-signaling, self-assembling GFs. Our peptide hydrogels are biocompatible and bind target IGF receptors in a dose-dependent fashion, activate proangiogenic signaling, and facilitate formation of angiogenic microtubules in vitro. Furthermore, infiltrated hydrogels are stable for weeks to months. We conclude that the enhanced targeting and long-term stability of our SAP/GF mimicry implants may improve the efficacy and safety of future GF mimic therapeutics.


Assuntos
Peptídeos Semelhantes à Insulina , Peptídeos , Peptídeos/química , Peptídeos e Proteínas de Sinalização Intercelular , Engenharia Tecidual , Hidrogéis/química
5.
Cureus ; 15(11): e48501, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38073988

RESUMO

Introduction The urology multidisciplinary team meeting (MDT) is the key weekly meeting that allows the opportunity to review results and discuss management plans for all urological cancers within a department. As populations age and cancer detection and management improve, the demand for the MDT will increase. We conducted a collaborative transregional study within the UK to evaluate the current workload on the urology MDT. Methods The study was divided into two parts: a multicenter retrospective audit and a snapshot survey. Three UK hospitals in Birmingham, Liverpool, and Cardiff were recruited into the multicenter study. Each hospital provided full MDT lists for all weekly meetings between August 2017 and 2022. Retrospective data gathered included the number of patients discussed per week, the average age of patients per week, the time allocated to their weekly MDT, and the total number of consultants in the department. The second part of the study involved the distribution of an online questionnaire to urologists across the UK to obtain a snapshot picture with the above parameters. Results Snapshot data from 34 different UK hospitals showed MDT length ranged from 1-6 hours, patients discussed ranged from 10-90 per week, and the maximum average discussion time was 3.8 minutes per case. Furthermore, 76% (N = 28/37) of respondents said unnecessary cases were discussed. Varied suggestions were provided on how the MDT could be improved. Multicenter five-year data showed a rise in mean total numbers of patients discussed per week in all centers: a 34.8% increase in Birmingham (from 34.5 patients to 46.5 patients), a 23.5% increase in Liverpool (27.2 patients to 33.6 patients), and a 38.8% increase in Cardiff (22.7 patients to 31.5 patients). Hours per meeting were Birmingham (2), Liverpool (3), and Cardiff (4), which meant the average minutes per patient discussion were Birmingham (2.6), Liverpool (5.4), and Cardiff (7.6). Conclusion There is a rapidly rising trend across UK regions for the number of patients being discussed in the urology MDT meeting. The MDT structure and function across the country are highly variable. There is consensus that the MDT discusses cases that are unnecessary, and this has been recognized for many years. Widespread implementation of the latest MDT management guidelines is urgently required to ensure MDT meetings are able to function effectively and efficiently into the future.

6.
Adv Theory Simul ; 6(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37122440

RESUMO

Chronic levels of inflammation lead to autoimmune diseases such as rheumatoid arthritis and atherosclerosis. A key molecular mediator responsible for the progression of these diseases is Chemokine C-C motif ligand 2 (CCL2), a homodimerized cytokine that dissociates into monomeric form and binds to the CCR2 receptor. CCL2, also known as monocyte chemoattractant protein-1 (MCP-1), attracts monocytes to migrate to areas of injury and mature into macrophages, leading to positive feedback inflammation with further release of proinflammatory molecules such as IL-1ß and TNF-α. Sequestering CCL2 to prevent its binding to CCR2 may prevent this inflammatory activity. Prior work adapted an α-helical CCL2-binding peptide (WKNFQTI) from murine CCR2 through extracellular loop analysis. Here, higher-affinity peptide binders were computationally designed through homology modeling and energy calculations, yielding an 11-amino acid peptide with high binding affinity. In addition, Rosetta mutations improved binding affinity in silico with blockage of the CCL2 dimerization site. Future work in analyzing binding kinetics and in vivo inflammation abrogation will confirm the accuracy of computational modeling techniques in de novo rational design of CCL2 cytokine binders.

7.
Brachytherapy ; 22(4): 542-546, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37217415

RESUMO

PURPOSE: To evaluate clinical outcomes of endobronchial malignancy treated using high-dose-rate endobronchial brachytherapy (HDREB). METHODS AND MATERIALS: A retrospective chart review was conducted for all patients treated with HDREB for malignant airway disease between 2010 and 2019 at a single institution. Most patients had a prescription of 14 Gy in two fractions given a week apart. The Wilcoxon signed rank test and paired samples t test were used to compare changes in mMRC dyspnea scale prior to and after brachytherapy at first followup appointment. Toxicity data were collected for dyspnea, hemoptysis, dysphagia, and cough. RESULTS: A total of 58 patients were identified. Most (84.5%) had primary lung cancer with advanced cancers, stage III or IV (86%). Eight were treated while admitted in the ICU. Previous external beam radiotherapy (EBRT) was received by 52%. An improvement in dyspnea was seen in 72%, with an mMRC dyspnoea scale score improvement of 1.13 points (p < 0.001). Most (22, 88%) had an improvement in hemoptysis and 18 out of 37 (48.6%) had an improvement in cough. Grade four to five events occurred in 8 (13%) at the median time of 2.5 months from brachytherapy. Twenty-two patients (38%) had complete obstruction of the airway treated. Median progression free survival was 6.5 months and median survival was 10 months. CONCLUSIONS: We report a significant symptomatic benefit among patients receiving brachytherapy with endobronchial malignancy, with rates of treatment related toxicities similar to prior studies. Our study identified new subgroups of patients, ICU patients & those with complete obstruction, who benefited from HDREB.


Assuntos
Braquiterapia , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Hemoptise/etiologia , Tosse/etiologia , Braquiterapia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Dosagem Radioterapêutica , Dispneia/etiologia
8.
Diseases ; 11(1)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36810548

RESUMO

BACKGROUND: Priapism is a very rare complication of malignancy and is usually accompanied by locally advanced or widely metastatic disease. We describe a case of priapism arising in a 46-year-old male with localised rectal cancer that was responding to therapy. CASE PRESENTATION: This patient had just completed two weeks of neoadjuvant, long-course chemoradiation when he presented with persistent painful penile erection. Assessment and diagnosis were delayed for more than 60 h, and although a cause could not be determined from imaging, a near complete radiological response of the primary rectal cancer was seen. His symptoms were refractory to urologic intervention and were associated with extreme psychological distress. He re-presented shortly thereafter with extensively metastatic disease in the lungs, liver, pelvis, scrotum, and penis; additionally, multiple venous thromboses were identified, including in the dorsal penile veins. His priapism was not reversible and was associated with a considerable symptom burden for the remainder of his life. His malignancy did not respond to first-line palliative chemotherapy or radiation, and his clinical course was further complicated by obstructive nephropathy, ileus, and genital skin breakdown with a suspected infection. We initiated comfort measures, and he ultimately died in hospital less than five months after his initial presentation. CONCLUSION: Priapism in cancer is usually related to tumour infiltration of the penis and corporal bodies resulting in poor venous and lymphatic drainage. The management is palliative and can include chemotherapy, radiation, surgical shunting, and potentially penectomy; however, conservative penis-sparing therapy may be reasonable in patients with limited life expectancy.

9.
Urologia ; 90(2): 407-414, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36346172

RESUMO

OBJECTIVE: COVID-19 resulted in Regional tiered restrictions being introduced across the UK with subsequent implications for planned and emergency surgical care. Specific to Merseyside, Tier 4, Tier 2 and Tier 5 restrictions were introduced in late 2020 and early 2021. The purpose of this study was to examine the nature and workload of emergency urological procedures during three different national lockdown Tiers in the North West of England. METHOD: A 3-month prospective study examining all emergency urological activity was conducted from November 2020 when Tier 4 restrictions were introduced and included Tier 2 restrictions in December and then concluded at the end of January 2021 when Tier 5 restrictions were in place. Data was obtained by identifying patients using the electronic theatre listing system. RESULTS: A total of 71 emergency cases were performed (24 in November (Tier 4), 28 in December (Tier 2), 19 in January 2021 (Tier 5)) with 15 different types of procedures performed. The most frequently performed procedure was stent insertion (36), followed by scrotal exploration (10). The least commonly performed procedure was suprapubic catheter insertion under general anaesthesia (1). One patient required transfer to a different hospital. In total 6 calls were made by general surgery and 3 by gynaecology for urgent urological assistance in theatre. Three urology patients returned to the theatre as emergencies following elective procedures. CONCLUSION: Unlike the Spring lockdown, acute urological presentations requiring operative intervention still presented daily. Of the 71 cases performed, most occurred in Tier 2. Stent insertion was the most commonly performed procedure, with the majority of the cases performed by registrars.


Assuntos
COVID-19 , Urologia , Humanos , Estudos Prospectivos , Procedimentos Cirúrgicos Urológicos/métodos , Pandemias , Controle de Doenças Transmissíveis , Reino Unido
10.
Macromol Biosci ; 22(7): e2200067, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35579914

RESUMO

Diabetes mellitus affects an increasing proportion of the population, and is projected to double by 2060. Comorbidities contribute to an interrupted healing process which is delayed, prolonged, and associated with increased susceptibility to infection and unresolved inflammation. This leads to chronic nonhealing wounds and potential amputation. Here, the use of a bioactive angiogenic peptide-based hydrogel, SLan, is examined to improve early wound healing in diabetic rats, and its performance is compared to clinically utilized biosynthetic peptide-based materials such as Puramatrix. Streptozotocin-treated diabetic rats underwent 8 mm biopsy wounding in their dorsum. Wounds are treated with either Low (1 w%) SLan, High (4 w%) SLan, phosphate buffered saline (PBS), Puramatrix, or K2 (an unfunctionalized nonbioactive control sequentially similar to SLan), covered with Tegaderm, and monitored on for a month; animals are sacrificed for histomorphic analyses and immunostaining. Pharmacokinetic analysis showing no trafficking of peptides from the wound into the circulation. SLan groups show similar wound contraction as control groups (Puramatrix, PBS, and K2), however, showing marked improvement in healing in earlier time points, including increased deposition of new mature blood vessels. Altogether the results suggest this material can be used to "jumpstart" the diabetic wound healing process.


Assuntos
Diabetes Mellitus Experimental , Hidrogéis , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Hidrogéis/farmacologia , Ratos , Cicatrização
11.
Pediatr Blood Cancer ; 69(9): e29697, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35373903

RESUMO

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT). METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40). RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Criança , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/etiologia , Neoplasias Embrionárias de Células Germinativas/radioterapia , Órgãos em Risco , Fótons/uso terapêutico , Terapia com Prótons/métodos , Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Testiculares
12.
Bioact Mater ; 14: 290-301, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35310357

RESUMO

The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics. This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest (CNC)-like cells (CNCLCs); these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells (iPSCs). CNC is the anterior region of the neural crest in vertebrate embryos, which contains the primordium of dental pulp cells or odontoblasts. The produced CNCLCs showed approximately 2.5-12,000-fold upregulations of major CNC marker genes. Furthermore, the CNCLCs exhibited remarkable odontoblastic differentiation ability, especially when treated with a combination of the fibroblast growth factors (FGFs) FGF4 and FGF9. The FGFs induced odontoblast marker genes by 1.7-5.0-fold, as compared to bone morphogenetic protein 4 (BMP4) treatment. In a mouse subcutaneous implant model, the CNCLCs briefly fated with FGF4 + FGF9 replicated dental pulp tissue characteristics, such as harboring odontoblast-like cells, a dentin-like layer, and vast neovascularization, induced by the angiogenic self-assembling peptide hydrogel (SAPH), SLan. SLan acts as a versatile biocompatible scaffold in the canal space. This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.

13.
Bioact Mater ; 14: 234-249, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35310358

RESUMO

The carious process leads to inflammation of pulp tissue. Current care options include root canal treatment or apexification. These procedures, however, result in the loss of tooth vitality, sensitivity, and healing. Pulp capping and dental pulp regeneration are continually evolving techniques to regenerate pulp tissue, avoiding necrosis and loss of vitality. Many studies have successfully employed stem/progenitor cell populations, revascularization approaches, scaffolds or material-based strategies for pulp regeneration. Here we outline advantages and disadvantages of different methods and techniques which are currently being used in the field of regenerative endodontics. We also summarize recent findings on efficacious peptide-based materials which target the dental niche.

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14.
Urol Int ; 106(7): 737-743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35235938

RESUMO

OBJECTIVE: The aim of this study is to review the literature on the use of antifungal prophylaxis in penile prosthesis (PP) surgery and provide a summary on its efficacy as an adjunct to current prophylactic regimes in patients undergoing PP surgery. MATERIALS AND METHODS: PubMed, Medline, and EMBASE databases were systematically searched up to May 2020. All included studies were analysed and the information extracted included author, title of study, year of publication, type of study, journal of publication, and main findings regarding post PP implantation fungal infections. RESULTS: Nine relevant studies were included in this review, comprising retrospective single-centre studies and retrospective multicentre studies ranging from 2017 to 2020. Fungal infections were found responsible for 11.1% of all PP infections, with a greater risk in patients with diabetes, obesity, and from warmer climates. Current American Urological Association (AUA) and European Association of Urology (EAU) prophylaxis guidelines do not incorporate the use of antifungals. Trials of antifungal prophylaxis regimes combined with antibiotic prophylaxis have demonstrated a reduction in PP fungal infections. CONCLUSIONS: Fungal infections represent a significant proportion of implant infections and therefore antifungal prophylaxis is warranted. Future studies comparing the efficacy of traditional antibiotic prophylaxis as set out by AUA/EAU with novel prophylaxis regimes including the addition of an antifungal may provide more definitive guidance on this issue. Until then antifungal prophylaxis in all patients undergoing PP procedures may provide a significant cost-effect benefit.


Assuntos
Micoses , Doenças do Pênis , Prótese de Pênis , Antifúngicos/uso terapêutico , Humanos , Masculino , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Estudos Retrospectivos
15.
Front Bioeng Biotechnol ; 10: 773004, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35155388

RESUMO

We have recently identified novel small molecules, Oxo-M and 4-PPBP, which specifically stimulate endogenous tendon stem/progenitor cells (TSCs), leading to potential regenerative healing of fully transected tendons. Here, we investigated an injectable, multidomain peptide (MDP) hydrogel providing controlled delivery of the small molecules for regenerative tendon healing. We investigated the release kinetics of Oxo-M and 4-PPBP from MDP hydrogels and the effect of MDP-released small molecules on tenogenic differentiation of TSCs and in vivo tendon healing. In vitro, MDP showed a sustained release of Oxo-M and 4-PPBP and a slower degradation than fibrin. In addition, tenogenic gene expression was significantly increased in TSC with MDP-released Oxo-M and 4-PPBP as compared to the fibrin-released. In vivo, MDP releasing Oxo-M and 4-PPBP significantly improved tendon healing, likely associated with prolonged effects of Oxo-M and 4-PPBP on suppression of M1 macrophages and promotion of M2 macrophages. Comprehensive analyses including histomorphology, digital image processing, and modulus mapping with nanoindentation consistently suggested that Oxo-M and 4-PPBP delivered via MDP further improved tendon healing as compared to fibrin-based delivery. In conclusion, MDP delivered with Oxo-M and 4-PPBP may serve as an efficient regenerative therapeutic for in situ tendon regeneration and healing.

16.
Bioengineering (Basel) ; 8(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34940343

RESUMO

Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period.

17.
Chem Eng J ; 4222021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34054331

RESUMO

One of the major constraints against using polymeric scaffolds as tissue-regenerative matrices is a lack of adequate implant vascularization. Self-assembling peptide hydrogels can sequester small molecules and biological macromolecules, and they can support infiltrating cells in vivo. Here we demonstrate the ability of self-assembling peptide hydrogels to facilitate angiogenic sprouting into polymeric scaffolds after subcutaneous implantation. We constructed two-component scaffolds that incorporated microporous polymeric scaffolds and viscoelastic nanoporous peptide hydrogels. Nanofibrous hydrogels modified the biocompatibility and vascular integration of polymeric scaffolds with microscopic pores (pore diameters: 100-250 µm). In spite of similar amphiphilic sequences, charges, secondary structures, and supramolecular nanostructures, two soft hydrogels studied herein had different abilities to aid implant vascularization, but had similar levels of cellular infiltration. The functional difference of the peptide hydrogels was predicted by the difference in the bioactive moieties inserted into the primary sequences of the peptide monomers. Our study highlights the utility of soft supramolecular hydrogels to facilitate host-implant integration and control implant vascularization in biodegradable polyester scaffolds in vivo. Our study provides useful tools in designing multi-component regenerative scaffolds that recapitulate vascularized architectures of native tissues.

18.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946364

RESUMO

Novel polyacrylamide gel electrolytes (PGEs) doped with nano carbons with enhanced electrochemical, thermal, and mechanical properties are presented. Carboxylated carbon nanotubes (fCNTs), graphene oxide sheets (GO), and the hybrid of fCNT/GO were embedded in the PGEs to serve as supercapacitor (SC) electrolytes. Thermal stability of the unmodified PGE increased with the addition of the nano carbons which led to lower capacitance degradation and longer cycling life of the SCs. The fCNT/GO-PGE showed the best thermal stability, which was 50% higher than original PGE. Viscoelastic properties of PGEs were also improved with the incorporation of GO and fCNT/GO. Oxygen-containing functional groups in GO and fCNT/GO hydrogen bonded with the polymer chains and improved the elasticity of PGEs. The fCNT-PGE demonstrated a slightly lower viscous strain uninform distribution of CNTs in the polymer matrix and the defects formed within. Furthermore, ion diffusion between GO layers was enhanced in fCNT/GO-PGE because fCNT decreased the aggregation of GO sheets and improved the ion channels, increasing the gel ionic conductivity from 41 to 132 mS cm-1. Finally, MnO2-based supercapacitors using PGE, fCNT-PGE, GO-PGE, and fCNT/GO-PGE electrolytes were fabricated with the electrode-specific capacitance measured to be 39.5, 65.5, 77.6, and 83.3 F·g-1, respectively. This research demonstrates the effectiveness of nano carbons as dopants in polymer gel electrolytes for property enhancements.

19.
Acta Biomater ; 126: 109-118, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33689817

RESUMO

Angiogenesis is critical for tissue healing and regeneration. Promoting angiogenesis in materials implanted within dental pulp after pulpectomy is a major clinical challenge in endodontics. We demonstrate the ability of acellular self-assembling peptide hydrogels to create extracellular matrix mimetic architectures that guide in vivo development of neovasculature and tissue deposition. The hydrogels possess facile injectability, as well as sequence-level functionalizability. We explore the therapeutic utility of an angiogenic hydrogel to regenerate vascularized pulp-like soft tissue in a large animal (canine) orthotopic model. The regenerated soft tissue recapitulates key features of native pulp, such as blood vessels, neural filaments, and an odontoblast-like layer next to dentinal tubules. Our study establishes angiogenic peptide hydrogels as potent scaffolds for promoting soft tissue regeneration in vivo. STATEMENT OF SIGNIFICANCE: A major challenge to endodontic tissue engineering is the lack of in situ angiogenesis within intracanal implants, especially after complete removal of the dental pulp. The lack of a robust vasculature in implants limit integration of matrices with the host tissue and regeneration of soft tissue. We demonstrate the development of an acellular material that promotes tissue revascularization in vivo without added growth factors, in a preclinical canine model of pulp-like soft-tissue regeneration. Such acellular biomaterials would facilitate pulp revascularization approaches in large animal models, and translation into human clinical trials.


Assuntos
Polpa Dentária , Hidrogéis , Animais , Materiais Biocompatíveis , Matriz Extracelular , Humanos , Hidrogéis/farmacologia , Engenharia Tecidual , Alicerces Teciduais
20.
Polymers (Basel) ; 13(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546275

RESUMO

Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) poses challenges to harvest as an intact organ, making it difficult to study disease processes such as breast cancer (BC) survival in BM, and to effective evaluation of drug response in BM. Furthermore, it is a challenge to develop 3D BM structures due to its weak physical properties, and complex hierarchical structure and cellular landscape. To address this, we leveraged 3D bioprinting to create a BM structure with varied methylcellulose (M): alginate (A) ratios. We selected hydrogels containing 4% (w/v) M and 2% (w/v) A, which recapitulates rheological and ultrastructural features of the BM while maintaining stability in culture. This hydrogel sustained the culture of two key primary BM microenvironmental cells found at the perivascular region, mesenchymal stem cells and endothelial cells. More importantly, the scaffold showed evidence of cell autonomous dedifferentiation of BC cells to cancer stem cell properties. This scaffold could be the platform to create BM models for various diseases and also for drug screening.

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