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1.
Cell Biochem Funct ; 42(4): e4058, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38783647

RESUMO

We aimed to evaluate the materials based on 4-methacryloxyethyl trimellitate anhydride/methyl methacrylate tri-n-butylborane (Super-bond [SB]) and nano hydroxyapatite (naHAp) for the repair of perforation at pulp chamber floor (PPF) in vitro and in vivo models. SB and naHAp were mixed in the mass ratio of 10% or 30% to produce naHAp/SB. Human periodontal ligament stem cells (HPDLSCs) were cultured on resin discs of SB or naHAp/SB to analyze the effects of naHAp/SB on cell adhesion, proliferation, and cementoblastic differentiation. A rat PPF model was treated with SB or naHAp/SB to examine the effects of naHAp/SB on the healing of defected cementum and periodontal ligament (PDL) at the site of PPF. HPDLSCs were spindle-shaped and adhered to all resin discs. Changing the resin from SB to naHAp/SB did not significantly alter cell proliferation. Both 10% and 30% naHAp/SB were more effective than SB in promoting cementoblastic differentiation of HPDLSCs. In the rat PPF model, 30% naHAp/SB was more effective than SB in promoting the formation Sharpey's fiber-like structures with expression of the PDL-related marker and cementum-like structures with expression of cementum-related markers. In conclusion, 30% naHAp/SB can be the new restorative material for PPF because it exhibited the abilities of adhering to dentin and healing of defected periodontal tissue.


Assuntos
Compostos de Boro , Durapatita , Metacrilatos , Ligamento Periodontal , Animais , Ratos , Humanos , Durapatita/química , Durapatita/farmacologia , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/citologia , Ligamento Periodontal/metabolismo , Compostos de Boro/farmacologia , Compostos de Boro/química , Metacrilatos/química , Metacrilatos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Masculino , Proliferação de Células/efeitos dos fármacos , Cavidade Pulpar/metabolismo , Cavidade Pulpar/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo , Células Cultivadas , Ratos Sprague-Dawley , Metilmetacrilatos/química , Metilmetacrilatos/farmacologia , Adesão Celular/efeitos dos fármacos
2.
PLoS One ; 19(5): e0304143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38781281

RESUMO

This study addressed enamel demineralization, a common complication in fixed orthodontic treatment, by evaluating a novel orthodontic adhesive with DMAHDM-PCL composite fibers. These fibers, produced through electrospinning, were incorporated into orthodontic adhesive to create experimental formulations at different concentrations and a control group. The study assessed antimicrobial properties, biosafety, and mechanical characteristics. New orthodontic adhesive exhibited significant bacteriostatic effects, reducing bacterial biofilm activity and concentrations. Incorporating 1% and 3% DMAHDM-PCL did not affect cytocompatibility. Animal tests confirmed no inflammatory irritation. Shear bond strength and adhesive residual index results indicated that antimicrobial fibers didn't impact bonding ability. In conclusion, orthodontic adhesives with 3% DMAHDM-PCL fibers are potential antimicrobial bonding materials, offering a comprehensive solution to enamel demineralization in orthodontic patients.


Assuntos
Cimentos Dentários , Poliésteres , Poliésteres/química , Cimentos Dentários/química , Cimentos Dentários/farmacologia , Animais , Biofilmes/efeitos dos fármacos , Metacrilatos/química , Metacrilatos/farmacologia , Humanos , Teste de Materiais
3.
Nano Lett ; 24(19): 5690-5698, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38700237

RESUMO

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.


Assuntos
Hidrogéis , Hidrogéis/química , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Feminino , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Imunoterapia , Gelatina/química , Metacrilatos/química , Metacrilatos/farmacologia , Neoplasias da Mama/imunologia
4.
Langmuir ; 40(21): 10957-10965, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38752656

RESUMO

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.


Assuntos
Antibacterianos , Polímeros , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Polímeros/química , Polímeros/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Incrustação Biológica/prevenção & controle , Escherichia coli/efeitos dos fármacos , Bivalves/química , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/farmacologia , Soroalbumina Bovina/química , Humanos , Metacrilatos/química , Metacrilatos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Indóis
5.
J Nanobiotechnology ; 22(1): 265, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760763

RESUMO

BACKGROUND: Pulp regeneration is a novel approach for the treatment of immature permanent teeth with pulp necrosis. This technique includes the combination of stem cells, scaffolds, and growth factors. Recently, stem cell-derived extracellular vesicles (EVs) have emerged as a new methodology for pulp regeneration. Emerging evidence has proven that preconditioning is an effective scheme to modify EVs for better therapeutic potency. Meanwhile, proper scaffolding is of great significance to protect EVs from rapid clearance and destruction. This investigation aims to fabricate an injectable hydrogel loaded with EVs from pre-differentiated stem cells from human exfoliated deciduous teeth (SHEDs) and examine their effects on pulp regeneration. RESULTS: We successfully employed the odontogenic induction medium (OM) of SHEDs to generate functional EV (OM-EV). The OM-EV at a concentration of 20 µg/mL was demonstrated to promote the proliferation and migration of dental pulp stem cells (DPSCs). The results revealed that OM-EV has a better potential to promote odontogenic differentiation of DPSCs than common EVs (CM-EV) in vitro through Alizarin red phalloidin, alkaline phosphatase staining, and assessment of the expression of odontogenic-related markers. High-throughput sequencing suggests that the superior effects of OM-EV may be attributed to activation of the AMPK/mTOR pathway. Simultaneously, we prepared a photocrosslinkable gelatin methacryloyl (GelMA) to construct an OM-EV-encapsulated hydrogel. The hydrogel exhibited sustained release of OM-EV and good biocompatibility for DPSCs. The released OM-EV from the hydrogel could be internalized by DPSCs, thereby enhancing their survival and migration. In tooth root slices that were subcutaneously transplanted in nude mice, the OM-EV-encapsulated hydrogel was found to facilitate dentinogenesis. After 8 weeks, there was more formation of mineralized tissue, as well as higher levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). CONCLUSIONS: The effects of EV can be substantially enhanced by preconditioning of SHEDs. The functional EVs from SHEDs combined with GelMA are capable of effectively promoting dentinogenesis through upregulating the odontogenic differentiation of DPSCs, which provides a promising therapeutic approach for pulp regeneration.


Assuntos
Diferenciação Celular , Polpa Dentária , Vesículas Extracelulares , Gelatina , Metacrilatos , Odontogênese , Regeneração , Células-Tronco , Dente Decíduo , Polpa Dentária/citologia , Humanos , Vesículas Extracelulares/química , Gelatina/química , Gelatina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Odontogênese/efeitos dos fármacos , Animais , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo , Regeneração/efeitos dos fármacos , Dente Decíduo/citologia , Metacrilatos/química , Metacrilatos/farmacologia , Camundongos , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Células Cultivadas , Hidrogéis/química , Hidrogéis/farmacologia , Movimento Celular/efeitos dos fármacos
6.
Clin Oral Investig ; 28(6): 323, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761310

RESUMO

OBJECTIVES: White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets. MATERIALS AND METHODS: Sixty commercially available stainless steel brackets were coated with TiO2 nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO2 nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO2 nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm. RESULTS: The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant. CONCLUSIONS: The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties. CLINICAL RELEVANCE: Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.


Assuntos
Antibacterianos , Aderência Bacteriana , Microscopia Eletrônica de Varredura , Nanotubos , Braquetes Ortodônticos , Fosforilcolina , Streptococcus mutans , Propriedades de Superfície , Titânio , Titânio/química , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Fosforilcolina/química , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/farmacologia , Nanotubos/química , Aderência Bacteriana/efeitos dos fármacos , Microscopia de Força Atômica , Teste de Materiais , Aço Inoxidável/química , Metacrilatos/farmacologia , Metacrilatos/química , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
7.
J Agric Food Chem ; 72(17): 9680-9690, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38634420

RESUMO

Plant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.


Assuntos
Botrytis , Carboxilesterase , Sistema Enzimático do Citocromo P-450 , Farmacorresistência Fúngica , Proteínas Fúngicas , Fungicidas Industriais , Pirimidinas , Estrobilurinas , Fungicidas Industriais/farmacologia , Fungicidas Industriais/metabolismo , Estrobilurinas/farmacologia , Estrobilurinas/metabolismo , Estrobilurinas/química , Pirimidinas/farmacologia , Pirimidinas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Botrytis/genética , Botrytis/efeitos dos fármacos , Carboxilesterase/metabolismo , Carboxilesterase/genética , Farmacorresistência Fúngica/genética , Doenças das Plantas/microbiologia , Metacrilatos/farmacologia , Metacrilatos/metabolismo
8.
ACS Biomater Sci Eng ; 10(5): 3306-3315, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38634810

RESUMO

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.


Assuntos
Técnicas de Cocultura , Fator 2 de Crescimento de Fibroblastos , Gelatina , Células Endoteliais da Veia Umbilical Humana , Hidrogéis , Metacrilatos , Engenharia Tecidual , Fator A de Crescimento do Endotélio Vascular , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Gelatina/química , Gelatina/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Engenharia Tecidual/métodos , Neovascularização Fisiológica/efeitos dos fármacos , Tecido Adiposo/citologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo , Células-Tronco/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
9.
Int J Biol Macromol ; 268(Pt 1): 131594, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38621568

RESUMO

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.


Assuntos
Alginatos , Quitosana , Células Endoteliais da Veia Umbilical Humana , Regeneração Nervosa , Células de Schwann , Quitosana/química , Quitosana/farmacologia , Alginatos/química , Alginatos/farmacologia , Animais , Humanos , Ratos , Regeneração Nervosa/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Microgéis/química , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Traumatismos dos Nervos Periféricos/terapia , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Alicerces Teciduais/química , Metacrilatos/química , Metacrilatos/farmacologia , Movimento Celular/efeitos dos fármacos
10.
Int J Biol Macromol ; 266(Pt 2): 131357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580010

RESUMO

The microenvironment of bone defect site is vital for bone regeneration. Severe bone defect is often accompanied with severe inflammation and elevated generation of reactive oxygen species (ROS) during bone repair. In recent years, the unfriendly local microenvironment has been paid more and more attention. Some bioactive materials with the ability to regulate the microenvironment to promote bone regeneration urgently need to be developed. Here, we develop a multifunctional composite hydrogel composed of photo-responsive methacrylate silk fibroin (SFMA), laponite (LAP) nanocomposite and tannic acid (TA), aiming to endow hydrogel with antioxidant, anti-inflammatory and osteogenic induction ability. Characterization results confirmed that the SFMA-LAP@TA hydrogel could significantly improve the mechanical properties of hydrogel. The ROS-Scavenging ability of the hydrogel enabled bone marrow mesenchymal stem cells (BMSCs) to survive against H2O2-induced oxidative stress. In addition, the SFMA-LAP@TA hydrogel effectively decreased the expression of pro-inflammatory factors in RAW264.7. More importantly, the SFMA-LAP@TA hydrogel could enhance the expression of osteogenic markers of BMSCs under inflammatory condition and greatly promote new bone formation in a critical-sized cranial defect model. Above all, the multifunctional hydrogel could effectively promote bone regeneration in vitro and in vivo by scavenging ROS and reducing inflammation, providing a prospective strategy for bone regeneration.


Assuntos
Regeneração Óssea , Fibroínas , Hidrogéis , Inflamação , Células-Tronco Mesenquimais , Nanocompostos , Osteogênese , Polifenóis , Espécies Reativas de Oxigênio , Taninos , Regeneração Óssea/efeitos dos fármacos , Animais , Fibroínas/química , Fibroínas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Taninos/química , Taninos/farmacologia , Camundongos , Inflamação/tratamento farmacológico , Nanocompostos/química , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células RAW 264.7 , Osteogênese/efeitos dos fármacos , Metacrilatos/química , Metacrilatos/farmacologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
11.
Int J Biol Macromol ; 269(Pt 1): 131826, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679256

RESUMO

The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by deposition of desmoplastic matrix (including collagen and hyaluronic acid). And the interactions between tumor-associated macrophages (TAMs) and tumor cells play a crucial role in progression of PDAC. Hence, the appropriate model of tumor cell-macrophage interaction within the unique PDAC TME is of significantly important. To this end, a 3D tumor niche based on dual-crosslinking gelatin methacrylate and hyaluronic acid methacrylate hydrogels was constructed to simulate the desmoplastic tumor matrix with matching compressive modulus and composition. The bionic 3D tumor niche creates an immunosuppressive microenvironment characterized by the downregulation of M1 markers and upregulation of M2 markers in TAMs. Mechanistically, RNA-seq analysis revealed that the PI3K-AKT signaling pathway might modulate the phenotypic balance and recruitment of macrophages through regulating SELE and VCAM-1. Furthermore, GO and GSEA revealed the biological process of leukocyte migration and the activation of cytokine-associated signaling were involved. Finally, the 3D tumor-macrophage niches with three different ratios were fabricated which displayed increased M2-like polarization and stemness. The utilization of the 3D tumor niche has the potential to provide a more accurate investigation of the interplay between PDAC tumor cells and macrophages within an in vivo setting.


Assuntos
Carcinoma Ductal Pancreático , Gelatina , Ácido Hialurônico , Metacrilatos , Microambiente Tumoral , Macrófagos Associados a Tumor , Gelatina/química , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Humanos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Metacrilatos/química , Metacrilatos/farmacologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Hidrogéis/química , Linhagem Celular Tumoral , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Transdução de Sinais/efeitos dos fármacos
12.
Biomacromolecules ; 25(5): 3131-3140, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38554085

RESUMO

The sulfated marine polysaccharides, fucoidan and λ-carrageenan, are known to possess anti-inflammatory, immunomodulatory, and cellular protective properties. Although they hold considerable promise for tissue engineering constructs, their covalent cross-linking in hydrogels and comparative bioactivities to cells are absent from the literature. Thus, fucoidan and λ-carrageenan were modified with methacrylate groups and were covalently cross-linked with the synthetic polymer poly(vinyl alcohol)-methacrylate (PVA-MA) to form 20 wt % biosynthetic hydrogels. Identical degrees of methacrylation were confirmed by 1H NMR, and covalent conjugation was determined by using a colorimetric 1,9-dimethyl-methylene blue (DMMB) assay. Pancreatic beta cells were encapsulated in the hydrogels, followed by culturing in the 3D environment for a prolonged period of 32 days and evaluation of the cellular functionality by live/dead, adenosine 5'-triphosphate (ATP) level, and insulin secretion. The results confirmed that fucoidan and λ-carrageenan exhibited ∼12% methacrylate substitution, which generated hydrogels with stable conjugation of the polysaccharides with PVA-MA. The cells encapsulated in the PVA-fucoidan hydrogels demonstrated consistently high ATP levels over the culture period. Furthermore, only cells in the PVA-fucoidan hydrogels retained glucose responsiveness, demonstrating comparatively higher insulin secretion in response to glucose. In contrast, cells in the PVA-λ-carrageenan and the PVA control hydrogels lost all glucose responsiveness. The present work confirms the superior effects of chemically modified fucoidan over λ-carrageenan on pancreatic beta cell survival and function in covalently cross-linked hydrogels, thereby illustrating the importance of differential polysaccharide structural features on their biological effects.


Assuntos
Carragenina , Hidrogéis , Polissacarídeos , Carragenina/química , Carragenina/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Álcool de Polivinil/química , Reagentes de Ligações Cruzadas/química , Ratos , Metacrilatos/química , Metacrilatos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Insulina/química , Insulina/metabolismo
13.
Int J Biol Macromol ; 266(Pt 2): 131231, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554918

RESUMO

The enormous potential of multifunctional bilayer wound dressings in various medical interventions for wound healing has led to decades of exploration into this field of medicine. However, it is usually difficult to synthesize a single hydrogel with all the required capabilities simultaneously. This paper proposes a bilayer model with an outer layer intended for hydrogel wound treatment. By adding gelatin methacrylate (GelMA) and tannic acid (TA) to the hydrogel composition and using polyvinyl alcohol-carboxymethyl chitosan (PVA-CMCs) foam layer as supports, a photocrosslinkable hydrogel with an optimal formulation was created. The hydrogels were then examined using a range of analytical procedures, including mechanical testing, rheology, chemical characterization, and in vitro and in vivo tests. The resulting bilayer wound dressing has many desirable properties, namely uniform adhesion and quick crosslinking by UV light. When used against Gram-positive and Gram-negative bacterial strains, bilayer wound dressings demonstrated broad antibacterial efficacy. In bilayer wound dressings with GelMA and TA, better wound healing was observed. Those without these elements showed less effectiveness in healing wounds. Additionally, encouraging collagen production and reducing wound infection has a major therapeutic impact on wounds. The results of this study could have a significant impact on the development of better-performing wound dressings.


Assuntos
Bandagens , Quitosana , Gelatina , Hidrogéis , Metacrilatos , Álcool de Polivinil , Cicatrização , Álcool de Polivinil/química , Gelatina/química , Gelatina/farmacologia , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Pele/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Taninos/química , Taninos/farmacologia , Reagentes de Ligações Cruzadas/química , Regeneração/efeitos dos fármacos , Camundongos , Ratos
14.
Int J Biol Macromol ; 265(Pt 1): 130868, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492687

RESUMO

The low oxygen environment of the periodontal pocket favors pathogenic anaerobes' growth, biofilm formation, and quick recurrence after periodontal treatment. In contrast, oxygen is detrimental to anaerobes, such as Porphyromonas gingivalis (P. gingivalis), since they lack a complete anti-oxidation mechanism to detoxify the oxygen challenge. Therefore, consistently feeding pathogenic anaerobes with abundant oxygen would be an effective strategy to combat them. Here, we reported injectable oxygen-generating hydrogels as oxygen mediators to alleviate the local anaerobic environment and eliminate periodontal pathogens. Gelatin methacrylate (GelMA) hydrogels loaded with calcium peroxide (CPO) possessed excellent injectability and exhibited burst releases of oxygen within 24 h with a 40 % oxygen tension peak. CPO-GelMA hydrogels with CPO concentrations of 5, 10, and 15 % reduced 60, 99, and 89.9 % viable P. gingivalis, respectively. Five percentage CPO-GelMA hydrogel downregulated gingipain and fimA gene expression in P. gingivalis without resistance development. Moreover, the CPO-GelMA hydrogels remarkably prevented biofilm formation and eradicated both monospecies and multispecies bacterial biofilms. In conclusion, CPO-GelMA hydrogels exert remarkable antimicrobial and antibiofilm effects on subgingival biofilms, providing a promising strategy for periodontal treatment.


Assuntos
Gelatina , Hidrogéis , Peróxidos , Hidrogéis/farmacologia , Gelatina/farmacologia , Metacrilatos/farmacologia , Oxigênio , Biofilmes
15.
Biomater Adv ; 159: 213826, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479241

RESUMO

Thermosensitive hydrogels based on the N-vinyl caprolactam (VCL), capable of allowing for cell adhesion and proliferation, as well as non-aggressive detachment by controlled temperature drop, were functionalized with 23 % or lower molar percentages of the cationizable hydrophobic unit 2-(diisopropylamino) ethyl methacrylate (DPAEMA), to obtain networks with dual sensitivity to temperature and pH. The swelling analysis of the systems has shown a transition pK (pKb) close to physiological values, dependent on the temperature of the medium (pKb of 6.6 and 6.9 when the temperature of the medium is above and below the transition temperature VPTT, respectively) and little dependence on the degree of functionalization of DPAEMA. In addition, at temperatures below the transition temperature (VPTT), the systems have shown large swelling variations as a function of the pH (i.e. below and above the pKb), exhibiting greater absorption capacity at pHs below pKb, where the DPAEMA units are cationized. Cytocompatibility and transplant capacity have been evaluated using the C166-GFP endothelial cell line. None of the thermosensitive hydrogels with variable DPAEMA content showed a delay with respect to the control without DPAEMA neither in terms of adhesion nor in proliferation. However, by increasing the percentage of DPAEMA functionalization -and decreasing thermosensitivity-, a correlative decrease in mitochondrial activity was obtained in the transplant, with significant differences for the hydrogels with DPAEMA molar percentage of 3 % or higher. Taking advantage of the proximity of the pKb to the physiological value, we have evaluated the cellular response and the capacity for transplantation after lowering the pH to 6.5, below pKb. A direct relationship of the DPAEMA functionalization degree on the detachment efficiency was observed, since the hydrogels with the highest molar load of DPAEMA showed higher mitochondrial metabolic activity after cell detachment.


Assuntos
Hidrogéis , Metacrilatos , Temperatura , Linhagem Celular , Metacrilatos/farmacologia , Metacrilatos/química , Interações Hidrofóbicas e Hidrofílicas
16.
ACS Biomater Sci Eng ; 10(3): 1620-1645, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38345020

RESUMO

Peripheral nerve injuries often result in substantial impairment of the neurostimulatory organs. While the autograft is still largely used as the "gold standard" clinical treatment option, nerve guidance conduits (NGCs) are currently considered a promising approach for promoting peripheral nerve regeneration. While several attempts have been made to construct NGCs using various biomaterial combinations, a comprehensive exploration of the process science associated with three-dimensional (3D) extrusion printing of NGCs with clinically relevant sizes (length: 20 mm; diameter: 2-8 mm), while focusing on tunable buildability using electroactive biomaterial inks, remains unexplored. In addressing this gap, we present here the results of the viscoelastic properties of a range of a multifunctional gelatin methacrylate (GelMA)/poly(ethylene glycol) diacrylate (PEGDA)/carbon nanofiber (CNF)/gellan gum (GG) hydrogel bioink formulations and printability assessment using experiments and quantitative models. Our results clearly established the positive impact of the gellan gum on the enhancement of the rheological properties. Interestingly, the strategic incorporation of PEGDA as a secondary cross-linker led to a remarkable enhancement in the strength and modulus by 3 and 8-fold, respectively. Moreover, conductive CNF addition resulted in a 4-fold improvement in measured electrical conductivity. The use of four-component electroactive biomaterial ink allowed us to obtain high neural cell viability in 3D bioprinted constructs. While the conventionally cast scaffolds can support the differentiation of neuro-2a cells, the most important result has been the excellent cell viability of neural cells in 3D encapsulated structures. Taken together, our findings demonstrate the potential of 3D bioprinting and multimodal biophysical cues in developing functional yet critical-sized nerve conduits for peripheral nerve tissue regeneration.


Assuntos
Bioimpressão , Polietilenoglicóis , Alicerces Teciduais , Alicerces Teciduais/química , Gelatina/química , Metacrilatos/farmacologia , Metacrilatos/química , Bioimpressão/métodos , Materiais Biocompatíveis/farmacologia , Regeneração Nervosa
17.
ACS Biomater Sci Eng ; 10(3): 1796-1807, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38346133

RESUMO

Dental resin composites (DRCs) are commonly used to restore teeth affected by dental caries or defects. These materials must possess excellent properties to withstand the complex oral environment. The objective of this study was to prepare and characterize Boron nitride nanosheets (BNN)/ dimethyl amino hexadecyl methacrylate (DMAHDM) composites (BNN/DMA), and to evaluate them as functional fillers to enhance the mechanical and antimicrobial properties of dental resins. The BNN/DMA composites were successfully prepared under the theoretical guidance of molecular dynamics (MD), and then the physicochemical and morphological characterization of the BNN/DMA composites were carried out by using various test methods, such as FT-IR, XRD, UV-vis spectroscopy, SEM, TEM, and AFM. It was doped into the dental flowable resin in a certain proportion, and the results showed that the flexural strength (FS), elastic modulus (EM), compressive strength (CS), and microhardness (MH) of the modified resin composites were increased by 53.29, 47.8, 97.59, and 37.1%, respectively, with the addition of 0.8 wt % of BNN/DMA composite fillers. It has a good inhibition effect on Streptococcus mutans, with an inhibition rate as high as 90.43%. Furthermore, this effect persists even after one month of aging. In conclusion, the modification of flowable resins with low-concentration BNN/DMA composites favorably integrates the mechanical properties and long-term antimicrobial activity of dental resins. At the same time, they have good biocompatibility and do not affect the aesthetics. The BNN/DMA composite modified flowable resin has the potential to become a new type of antimicrobial dental restorative material.


Assuntos
Compostos de Amônio , Anti-Infecciosos , Compostos de Boro , Cárie Dentária , Humanos , Teste de Materiais , Espectroscopia de Infravermelho com Transformada de Fourier , Anti-Infecciosos/farmacologia , Metacrilatos/farmacologia , Metacrilatos/química , Resinas Compostas/farmacologia , Resinas Compostas/química
18.
Braz Oral Res ; 38: e001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38198301

RESUMO

The aim of this study was to evaluate the influence of adding quaternary ammonium methacrylates (QAMs) to experimental adhesives by assessing the degree of conversion (DC), cytotoxicity against keratinocytes and fibroblasts, and antibacterial activity against biofilm formation. Two QAMs were added to an experimental adhesive: dimethylaminododecyl methacrylate bromododecane (DMADDM) or dimethylaminododecyl methacrylate bromohexadecane (DMAHDM) at three concentrations each: 1, 2.5, and 5 wt.%. Experimental adhesive without QAMs (control group) and commercially available Transbond XT Primer (3M Unitek, Monrovia, California, USA) were used for comparisons. The adhesives were tested for DC, cytotoxicity against keratinocytes and fibroblasts, and antibacterial activity against biofilm formation. DC, cytotoxicity against fibroblasts, and antibacterial activity were analyzed using one-way ANOVA and Tukey's multiple comparisons. Cytotoxicity against keratinocytes was evaluated using the Kruskal Wallis and Dunn's post-hoc (α = 5%) tests. Transbond showed lower DC as compared to 5% DMAHDM, 1% DMADDM, and 5% DMADDM (p < 0.05). However, all groups presented proper DC when compared to commercial adhesives in the literature. In the evaluation of cytotoxicity against keratinocytes, Transbond induced higher viability than 2.5 wt.% groups (p < 0.05). Against fibroblasts, Transbond induced higher viability as compared to 5 wt.% groups (p < 0.05). DMAHDM at 5 wt.% reduced biofilm formation when compared to all the other groups (p < 0.05). Despite their cytotoxic effect against keratinocytes, gingival fibroblasts showed higher viability. DMAHDM at 5 wt.% decreased Streptococcus mutans viability. The incorporation of DMAHDM at 5 wt.% may be a strategy for reducing the development of white spot lesions.


Assuntos
Antibacterianos , Bis-Fenol A-Glicidil Metacrilato , Hidrocarbonetos Bromados , Metacrilatos , Metilaminas , Compostos de Amônio Quaternário , Metacrilatos/farmacologia , Antibacterianos/farmacologia
19.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(1): 45-53, 2024 Jan 09.
Artigo em Chinês | MEDLINE | ID: mdl-38172061

RESUMO

Objective: To explore the application prospect of a new pH-responsive tertiary amine monomer dodecylmethylaminoethyl methacrylate (DMAEM) modified resin adhesive (DMAEM@RA) in the prevention and treatment of secondary caries. Methods: Five percents DMAEM was added to the resin adhesive to synthesize DMAEM@RA for modifying. Streptococcus mutans (Sm) and Lactobacillus casei (Lc) biofilms were cultured on resin adhesive and DMAEM@RA, respectively. The culture systems were set up at pH=7.4, 6.0, 5.5, and 5.0. The antimicrobial activity of DMAEM@RA was evaluated by quantitative PCR. The effects of DMAEM@RA on biofilm thickness, bacterial amount, and extracellular polysaccharides were studied by scanning electron microscope (SEM) and extracellular polysaccharide staining. Real-time fluorescence quantitative PCR was used to study the effect of DMAEM@RA on the expression levels of cariogenic genes in Sm. Results: DMAEM@RA could significantly reduce the amount of Sm and Lc under acidic conditions, especially Lc. At pH=5.0, the logarithm value of co-cultured Sm bacteria [lg (CFU/ml)] in DMAEM@RA group (7.58±0.01) was significantly lower than that in control group (7.87±0.03) (t=14.32, P<0.001), and the logarithm value of Lc bacteria [lg (CFU/ml)] (7.29±0.04) was also significantly lower than that in control group (7.93±0.15) (t=6.93, P=0.002). SEM observed that the bacteria decreased and the cell fragments appeared in DMAEM@RA group. In addition, DMAEM@RA significantly reduced the biomass of extracellular polysaccharides in the dual-species biofilm under acidic conditions. At pH=5.0, the biomass of extracellular polysaccharides in DMAEM@RA group [(25.13±3.14) mm3/mm2] was significantly lower than that in the control group [(42.66±7.46) mm3/mm2] (t=3.75, P=0.020). DMAEM@RA could significantly up-regulate the expressions of gtfB and gtfC genes in Sm under acidic conditions. At pH=5.0, gtfB and gtfC genes were significantly up-regulated by (14.64± 0.44) times and (2.99±0.20) times, respectively (t=-42.74, P<0.001; t=-13.55, P<0.001). Conclusions: The DMAEM@RA has a good antibacterial effect under acidic conditions, demonstrating that it has a good potential to prevent the occurrence and development of secondary caries.


Assuntos
Cárie Dentária , Lacticaseibacillus casei , Humanos , Streptococcus mutans , Metacrilatos/farmacologia , Metacrilatos/metabolismo , Cimentos Dentários , Cárie Dentária/prevenção & controle , Cárie Dentária/microbiologia , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Aminas/metabolismo , Aminas/farmacologia , Biofilmes , Concentração de Íons de Hidrogênio
20.
J Mater Chem B ; 12(3): 814-827, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38189164

RESUMO

Polymerisation shrinkage and biofilm accumulation are the two main problems associated with dental resin composites (DRCs) that induce secondary caries, which can cause restoration failure. Polymerisation shrinkage can lead to microleakage gaps between the tooth and the DRCs, causing the aggregation of bacteria and development of secondary caries. Reducing the shrinkage stress (SS) and improving the resistance to bacterial adhesion have always been the focus of this field in modifying DRCs. A thiol-ene resin system can effectively reduce the polymerisation SS via its step-growth mechanism for delaying the gel point. Fluorinated compounds can reduce the surface free energies, thereby reducing bacterial adhesion. Thus, in this study, a range of mass fractions (0, 10, 20, 30, and 40 wt%) of a fluorinated thiol-ene resin system were added to a fluorinated dimethacrylate resin system/tricyclo decanedimethanol diacrylate to create a fluorinated methacrylate-thiol-ene ternary resin matrix. DRCs were prepared using the obtained ternary resin matrix, and their physical and chemical properties, effect on bacterial adhesion, and biocompatibility were investigated. The results demonstrated that the volumetric shrinkage and SS of the DRCs were reduced with no reduction in conversion degree even after the thiol-ene resin system was added. All DRC-based fluorinated resin systems exhibited an excellent anti-bacterial adhesion effect, as evidenced by the colony-forming unit counts, live/dead bacterial staining, and crystal violet staining tests against Streptococcus mutans (S. mutans). The genetic expressions associated with the bacterial adhesion of S. mutans were substantially affected after being cultured with fluorinated DRCs. All fluorinated DRCs demonstrated good biocompatibility through the in vitro cytotoxicity test and live/dead staining images of the L-929 cells. The above results illustrate that the DRCs based on the fluorinated methacrylate-thiol-ene resin matrix can be potentially applied in clinical practice due to their low SS and anti-bacterial adhesion effect.


Assuntos
Resinas Compostas , Metacrilatos , Resinas Compostas/farmacologia , Teste de Materiais , Metacrilatos/farmacologia , Metacrilatos/química , Compostos de Sulfidrila/química , Bactérias
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