RESUMO
Two-dimensional (2D) molybdenum disulfide (MoS2) nanomaterials are an emerging class of biomaterials that are photoresponsive at near-infrared wavelengths (NIR). Here, we demonstrate the ability of 2D MoS2 to modulate cellular functions of human stem cells through photothermal mechanisms. The interaction of MoS2 and NIR stimulation of MoS2 with human stem cells is investigated using whole-transcriptome sequencing (RNA-seq). Global gene expression profile of stem cells reveals significant influence of MoS2 and NIR stimulation of MoS2 on integrins, cellular migration, and wound healing. The combination of MoS2 and NIR light may provide new approaches to regulate and direct these cellular functions for the purposes of regenerative medicine as well as cancer therapy.
Assuntos
Dissulfetos/efeitos da radiação , Células-Tronco Mesenquimais/efeitos da radiação , Molibdênio/efeitos da radiação , Nanoestruturas/efeitos da radiação , Adesão Celular/efeitos da radiação , Movimento Celular/efeitos da radiação , Sobrevivência Celular , Dissulfetos/química , Dissulfetos/metabolismo , Perfilação da Expressão Gênica , Humanos , Raios Infravermelhos , Integrinas/genética , Integrinas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Molibdênio/química , Molibdênio/metabolismo , Nanoestruturas/química , Fármacos Fotossensibilizantes , Transdução de Sinais/efeitos da radiaçãoRESUMO
Alginate hydrogels are widely used for tissue engineering and regenerative medicine due to their excellent biocompatibility. A facile and commonly used strategy to crosslink alginate is the addition of Ca2+ that leads to hydrogelation. However, extracellular Ca2+ is a secondary messenger in activating inflammasome pathways following physical injury or pathogenic insult, which carries the risk of persistent inflammation and scaffold rejection. Here, we present graft copolymers of charge complementary heterodimeric coiled coil (CC) peptides and alginate that undergo supramolecular self-assembly to form Ca2+ free alginate hydrogels. The formation of heterodimeric CCs was confirmed using circular dichroism spectroscopy, and scanning electron microscopy revealed a significant difference in crosslink density and homogeneity between Ca2+ and CC crosslinked gels. The resulting hydrogels were self-supporting and display shear-thinning and shear-recovery properties. In response to lipopolysaccharide (LPS) stimulation, peritoneal macrophages and bone marrow-derived dendritic cells cultured in the CC crosslinked gels exhibited a 10-fold reduction in secretion of the proinflammatory cytokine IL-1ß compared to Ca2+ crosslinked gels. A similar response was also observed in vivo upon peritoneal delivery of Ca2+ or CC crosslinked gels. Analysis of peritoneal lavage showed that macrophages in mice injected with Ca2+ crosslinked gels display a more inflammatory phenotype compared to macrophages from mice injected with CC crosslinked gels. These results suggest that CC peptides by virtue of their tunable sequence-structure-function relationship and mild gelation conditions are promising alternative crosslinkers for alginate and other biopolymer scaffolds used in tissue engineering.
Assuntos
Alginatos , Hidrogéis , Alginatos/química , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Inflamação/patologia , Macrófagos/patologia , Camundongos , Engenharia Tecidual/métodosRESUMO
Two-dimensional (2D) nanomaterials are an emerging class of biomaterials with remarkable potential for biomedical applications. The planar topography of these nanomaterials confers unique physical, chemical, electronic and optical properties, making them attractive candidates for therapeutic delivery, biosensing, bioimaging, regenerative medicine, and additive manufacturing strategies. The high surface-to-volume ratio of 2D nanomaterials promotes enhanced interactions with biomolecules and cells. A range of 2D nanomaterials, including transition metal dichalcogenides (TMDs), layered double hydroxides (LDHs), layered silicates (nanoclays), 2D metal carbides and nitrides (MXenes), metal-organic framework (MOFs), covalent organic frameworks (COFs) and polymer nanosheets have been investigated for their potential in biomedical applications. Here, we will critically evaluate recent advances of 2D nanomaterial strategies in biomedical engineering and discuss emerging approaches and current limitations associated with these nanomaterials. Due to their unique physical, chemical, and biological properties, this new class of nanomaterials has the potential to become a platform technology in regenerative medicine and other biomedical applications.
RESUMO
Patterned substitution of d-amino acids into the primary sequences of self-assembling peptides influences molecular-level packing and supramolecular morphology. We report that block heterochiral analogs of the model amphipathic peptide KFE8 (Ac-FKFEFKFE-NH2), composed of two FKFE repeat motifs with opposite chirality, assemble into helical tapes with dimensions greatly exceeding those of their fibrillar homochiral counterparts. At sufficient concentrations, these tapes form hydrogels with reduced storage moduli but retain the shear-thinning behavior and consistent mechanical recovery of the homochiral analogs. Varying the identity of charged residues (FRFEFRFE and FRFDFRFD) produced similarly sized nonhelical tapes, while a peptide with nonenantiomeric l- and d-blocks (FKFEFRFD) formed helical tapes closely resembling those of the heterochiral KFE8 analogs. A proposed energy-minimized model suggests that a kink at the interface between l- and d-blocks leads to the assembly of flat monolayers with nonidentical surfaces that display alternating stacks of hydrophobic and charged groups.
Assuntos
Peptídeos/química , Sequência de Aminoácidos , Dicroísmo Circular , Hidrogéis/química , Peptídeos/metabolismo , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Reologia , Espalhamento a Baixo Ângulo , Estereoisomerismo , Difração de Raios XRESUMO
Flexible electronics require elastomeric and conductive biointerfaces with native tissue-like mechanical properties. The conventional approaches to engineer such a biointerface often utilize conductive nanomaterials in combination with polymeric hydrogels that are cross-linked using toxic photoinitiators. Moreover, these systems frequently demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. To address these challenges, we developed a class of shear-thinning hydrogels as biomaterial inks for 3D printing flexible bioelectronics. These hydrogels are engineered through a facile vacancy-driven gelation of MoS2 nanoassemblies with naturally derived polymer-thiolated gelatin. Due to shear-thinning properties, these nanoengineered hydrogels can be printed into complex shapes that can respond to mechanical deformation. The chemically cross-linked nanoengineered hydrogels demonstrate a 20-fold rise in compressive moduli and can withstand up to 80% strain without permanent deformation, meeting human anatomical flexibility. The nanoengineered network exhibits high conductivity, compressive modulus, pseudocapacitance, and biocompatibility. The 3D-printed cross-linked structure demonstrates excellent strain sensitivity and can be used as wearable electronics to detect various motion dynamics. Overall, the results suggest that these nanoengineered hydrogels offer improved mechanical, electronic, and biological characteristics for various emerging biomedical applications including 3D-printed flexible biosensors, actuators, optoelectronics, and therapeutic delivery devices.
Assuntos
Hidrogéis , Tinta , Humanos , Hidrogéis/química , Impressão Tridimensional , Condutividade Elétrica , Gelatina , PolímerosRESUMO
Light-responsive biomaterials are an emerging class of materials used for developing noninvasive, noncontact, precise, and controllable biomedical devices. Long-wavelength near-infrared (NIR) radiation is an attractive light source for in situ gelation due to its higher penetration depth and minimum side effects. The conventional approach to obtain crosslinked biomaterials relies heavily on the use of a photoinitiator by generating reactive species when exposed to short-wavelength radiation, which is detrimental to surrounding cells and tissue. Here, a new class of NIR-triggered in situ gelation system based on defect-rich 2D molybdenum disulfide (MoS2 ) nanoassemblies and thiol-functionalized thermoresponsive polymer in the absence of a photoinitiator is introduced. Exposure to NIR radiation activates the dynamic polymer-nanomaterials interactions by leveraging the photothermal characteristics of MoS2 and intrinsic phase transition ability of the thermoresponsive polymer. Specifically, upon NIR exposure, MoS2 acts as a crosslink epicenter by connecting with multiple polymeric chains via defect-driven click chemistry. As a proof-of-concept, the utility of NIR-triggered in situ gelation is demonstrated in vitro and in vivo. Additionally, the crosslinked gel exhibits the potential for NIR light-responsive release of encapsulated therapeutics. These light-responsive biomaterials have strong potential for a range of biomedical applications, including artificial muscle, smart actuators, 3D/4D printing, regenerative medicine, and therapeutic delivery.
Assuntos
Dissulfetos , Molibdênio , Hidrogéis , FototerapiaRESUMO
Platelets extravasate from the circulation into tumor microenvironment, enable metastasis, and confer resistance to chemotherapy in several cancers. Therefore, arresting tumor-platelet cross-talk with effective and atoxic antiplatelet agents in combination with anticancer drugs may serve as an effective cancer treatment strategy. To test this concept, we create an ovarian tumor microenvironment chip (OTME-Chip) that consists of a platelet-perfused tumor microenvironment and which recapitulates platelet extravasation and its consequences. By including gene-edited tumors and RNA sequencing, this organ-on-chip revealed that platelets and tumors interact through glycoprotein VI (GPVI) and tumor galectin-3 under shear. Last, as proof of principle of a clinical trial, we showed that a GPVI inhibitor, Revacept, impairs metastatic potential and improves chemotherapy. Since GPVI is an antithrombotic target that does not impair hemostasis, it represents a safe cancer therapeutic. We propose that OTME-Chip could be deployed to study other vascular and hematological targets in cancer.
Assuntos
Neoplasias Ovarianas , Inibidores da Agregação Plaquetária , Plaquetas , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Microambiente TumoralRESUMO
We introduced a new concept to the control of wetting characteristics by modulating the degree of atomic defects of two-dimensional transition metal dichalcogenide nanoassemblies of molybdenum disulfide. This work shed new light on the role of atomic vacancies on wetting characteristic that can be leveraged to develop a new class of superhydrophobic surfaces for various applications without altering their topography.
Assuntos
Adesão Celular , Dissulfetos/química , Células-Tronco Mesenquimais/fisiologia , Molibdênio/química , Nanoestruturas/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , MolhabilidadeRESUMO
We report injectable nanoengineered hemostats for enhanced wound healing and tissue regeneration. The nanoengineered system consists of the natural polysaccharide, κ-carrageenan (κCA), loaded with synthetic two-dimensional (2D) nanosilicates. Nanoengineered hydrogels showed shear-thinning characteristics and can be injected for minimally invasive approaches. The injectable gels can be physically crosslinked in presence of monovalent ions to form mechanically strong hydrogels. By controlling the ratio between κCA and nanosilicates, compressive stiffness of crosslinked hydrogels can be modulated between 20 and 200â¯kPa. Despite high mechanical stiffness, nanocomposite hydrogels are highly porous with an interconnected network. The addition of nanosilicates to κCA increases protein adsorption on nanocomposite hydrogels that results in enhance cell adhesion and spreading, increase platelets binding and reduce blood clotting time. Moreover, due to presence of nanosilicates, a range of therapeutic biomacromolecules can be deliver in a sustain manner. The addition of nanosilicates significantly suppresses the release of entrap vascular endothelial growth factor (VEGF) and facilitate in vitro tissue regeneration and wound healing. Thus, this multifunctional nanocomposite hydrogel can be used as an injectable hemostat and an efficient vehicle for therapeutic delivery to facilitate tissue regeneration. STATEMENT OF SIGNIFICANCE: Hemorrhage is a leading cause of death in battlefield wounds, anastomosis hemorrhage and percutaneous intervention. Thus, there is a need for the development of novel bioactive materials to reduce the likelihood of hemorrhagic shock stemming from internal wounds. Here, we introduce an injectable hemostat from kappa-carrageenan and two-dimensional (2D) nanosilicates. Nanosilicates mechanically reinforce the hydrogels, provide enhanced physiological stability and accelerate the clotting time by two-fold. The sustained release of entrapped therapeutics due to presence of nanosilicates promotes enhanced wound healing. The multifunctional nanocomposite hydrogels could be used as an injectable hemostat for penetrating injury and percutaneous intervention during surgery.
Assuntos
Carragenina , Hidrogéis , Células-Tronco Mesenquimais/metabolismo , Nanocompostos/química , Cicatrização/efeitos dos fármacos , Carragenina/química , Carragenina/farmacologia , Adesão Celular/efeitos dos fármacos , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/patologia , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
Nanoengineered biomaterials have dramatically expanded the range of tools used for infection control and to accelerate wound healing. This review thoroughly describes the developments that are shaping this emerging field and evaluates the potential wound healing applications of recently developed engineered nanomaterials for both acute and chronic wounds. Specifically, we will assess the unique characteristics of engineered nanomaterials that render them applicable for wound healing and infection control. A range of engineered nanomaterials, including polymeric-, metallic- and ceramic-based nanomaterials, that could be used as therapeutic delivery agents to accelerate regeneration of damaged dermal and epidermal tissues are also detailed. Finally, we will detail the current state of engineered nanomaterials for wound regeneration and will identify promising new research directions in infection control.