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Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic-co-glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an in vitro cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.
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Neurological disorders have for a long time been a global challenge dismissed by drug companies, especially due to the low efficiency of most therapeutic compounds to cross the brain capillary wall, that forms the blood-brain barrier (BBB) and reach the brain. This has boosted an incessant search for novel carriers and methodologies to drive these compounds throughout the BBB. However, it remains a challenge to artificially mimic the physiology and function of the human BBB, allowing a reliable, reproducible and throughput screening of these rapidly growing technologies and nanoformulations (NFs). To surpass these challenges, brain-on-a-chip (BoC) - advanced microphysiological platforms that emulate key features of the brain composition and functionality, with the potential to emulate pathophysiological signatures of neurological disorders, are emerging as a microfluidic tool to screen new brain-targeting drugs, investigate neuropathogenesis and reach personalized medicine. In this review, the advance of BoC as a bioengineered screening tool of new brain-targeting drugs and NFs, enabling to decipher the intricate nanotechnology-biology interface is discussed. Firstly, the main challenges to model the brain are outlined, then, examples of BoC platforms to recapitulate the neurodegenerative diseases and screen NFs are summarized, emphasizing the current most promising nanotechnological-based drug delivery strategies and lastly, the integration of high-throughput screening biosensing systems as possible cutting-edge technologies for an end-use perspective is discussed as future perspective.
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Barreira Hematoencefálica , Encéfalo , Dispositivos Lab-On-A-Chip , Nanotecnologia , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Barreira Hematoencefálica/metabolismo , Nanotecnologia/métodos , Encéfalo/metabolismo , Animais , Sistemas de Liberação de Medicamentos/métodosRESUMO
Biological motions of native muscle tissues rely on the nervous system to interface movement with the surrounding environment. The neural innervation of muscles, crucial for regulating movement, is the fundamental infrastructure for swiftly responding to changes in body tissue requirements. This study introduces a bioelectronic neuromuscular robot integrated with the motor nervous system through electrical synapses to evoke cardiac muscle activities and steer robotic motion. Serving as an artificial brain and wirelessly regulating selective neural activation to initiate robot fin motion, a wireless frequency multiplexing bioelectronic device is used to control the robot. Frequency multiplexing bioelectronics enables the control of the robot locomotion speed and direction by modulating the flapping of the robot fins through the wireless motor innervation of cardiac muscles. The robots demonstrated an average locomotion speed of ~0.52 ± 0.22 millimeters per second, fin-flapping frequency up to 2.0 hertz, and turning locomotion path curvature of ~0.11 ± 0.04 radians per millimeter. These systems will contribute to the expansion of biohybrid machines into the brain-to-motor frontier for developing autonomous biohybrid systems capable of advanced adaptive motor control and learning.
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Desenho de Equipamento , Robótica , Tecnologia sem Fio , Robótica/instrumentação , Tecnologia sem Fio/instrumentação , Junção Neuromuscular/fisiologia , Humanos , Locomoção/fisiologia , Coração/fisiologia , Coração/inervação , Animais , Movimento (Física)RESUMO
Engineering biomimetic tissue implants with human induced pluripotent stem cells (hiPSCs) holds promise for repairing volumetric tissue loss. However, these implants face challenges in regenerative capability, survival, and geometric scalability at large-scale injury sites. Here, we present scalable vessel-integrated muscle-like lattices (VMLs), containing dense and aligned hiPSC-derived myofibers alongside passively perfusable vessel-like microchannels inside an endomysium-like supporting matrix using an embedded multimaterial bioprinting technology. The contractile and millimeter-long myofibers are created in mechanically tailored and nanofibrous extracellular matrix-based hydrogels. Incorporating vessel-like lattice enhances myofiber maturation in vitro and guides host vessel invasion in vivo, improving implant integration. Consequently, we demonstrate successful de novo muscle formation and muscle function restoration through a combinatorial effect between improved graft-host integration and its increased release of paracrine factors within volumetric muscle loss injury models. The proposed modular bioprinting technology enables scaling up to centimeter-sized prevascularized hiPSC-derived muscle tissues with custom geometries for next-generation muscle regenerative therapies.
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Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.
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Antibacterianos , Quitina , Sistemas de Liberação de Medicamentos , Hidrogéis , Nanopartículas , Impressão Tridimensional , Hidrogéis/química , Hidrogéis/farmacologia , Quitina/química , Quitina/farmacologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Animais , Periodontite/tratamento farmacológico , Periodontite/terapia , Periodontite/microbiologia , Periodontite/patologia , Sinvastatina/farmacologia , Sinvastatina/química , Sinvastatina/administração & dosagem , Células-Tronco Mesenquimais/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacosRESUMO
Skeletal muscle connective tissue (MCT) surrounds myofiber bundles to provide structural support, produce force transduction from tendons, and regulate satellite cell differentiation during muscle regeneration. Engineered muscle tissue composed of myofibers layered within MCT has not yet been developed. Herein, a bioengineering strategy to create MCT-layered myofibers through the development of stem cell fate-controlling biomaterials that achieve both myogenesis and fibroblast differentiation in a locally controlled manner at the single construct is introduced. The reciprocal role of transforming growth factor-beta 1 (TGF-ß1) and its inhibitor as well as 3D matrix stiffness to achieve co-differentiation of MCT fibroblasts and myofibers from a human-induced pluripotent stem cell (hiPSC)-derived paraxial mesoderm is studied. To avoid myogenic inhibition, TGF-ß1 is conjugated on the gelatin-based hydrogel to control the fibroblasts' populations locally; the TGF-ß1 degrades after 2 weeks, resulting in increased MCT-specific extracellular matrix (ECM) production. The locations of myofibers and fibroblasts are precisely controlled by using photolithography and co-axial wet spinning techniques, which results in the formation of MCT-layered functional myofibers in 3D constructs. This advanced engineering strategy is envisioned as a possible method for obtaining biomimetic human muscle grafts for various biomedical applications.
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Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.
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Hidrogéis , Infarto do Miocárdio , Oxigênio , Seda , Animais , Infarto do Miocárdio/patologia , Infarto do Miocárdio/tratamento farmacológico , Seda/química , Hidrogéis/química , Oxigênio/química , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Injeções , Cardiotônicos/farmacologia , Cardiotônicos/administração & dosagem , Cardiotônicos/química , Quimiocina CXCL12/administração & dosagem , Quimiocina CXCL12/farmacologia , Quimiocina CXCL12/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , RatosRESUMO
Noninvasive monitoring of biofabricated tissues during the biomanufacturing process is needed to obtain reproducible, healthy, and functional tissues. Measuring the levels of biomarkers secreted from tissues is a promising strategy to understand the status of tissues during biofabrication. Continuous and real-time information from cultivated tissues enables users to achieve scalable manufacturing. Label-free biosensors are promising candidates for detecting cell secretomes since they can be noninvasive and do not require labor-intensive processes such as cell lysing. Moreover, most conventional monitoring techniques are single-use, conducted at the end of the fabrication process, and, challengingly, are not permissive to in-line and continual detection. To address these challenges, we developed a noninvasive and continual monitoring platform to evaluate the status of cells during the biofabrication process, with a particular focus on monitoring the transient processes that stem cells go through during in vitro differentiation over extended periods. We designed and evaluated a reusable electrochemical immunosensor with the capacity for detecting trace amounts of secreted osteogenic markers, such as osteopontin (OPN). The sensor has a low limit of detection (LOD), high sensitivity, and outstanding selectivity in complex biological media. We used this OPN immunosensor to continuously monitor on-chip osteogenesis of human mesenchymal stem cells (hMSCs) cultured 2D and 3D hydrogel constructs inside a microfluidic bioreactor for more than a month and were able to observe changing levels of OPN secretion during culture. The proposed platform can potentially be adopted for monitoring a variety of biological applications and further developed into a fully automated system for applications in advanced cellular biomanufacturing.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Dispositivos Lab-On-A-Chip , Osteogênese , Humanos , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Osteopontina/análise , Osteopontina/metabolismo , Células-Tronco Mesenquimais/citologia , Imunoensaio/métodos , Imunoensaio/instrumentaçãoRESUMO
Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization. Here, we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel. The composite hydrogel (G-TSrP) is created by combining gelatin methacryloyl (GelMA) and nanoparticles (TSrP) composed of tannic acid (TA) and Sr2+. These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation. G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype. It has been observed that the liberation of TA and Sr2+ from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages, and thereby, coordinate in vivo adapted degradation of the G-TSrP. Most significantly, G-TSrP accelerates angiogenesis despite the TA's inhibitory properties, which are counteracted by the released Sr2+. Moreover, G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth. Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel. Collectively, these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.
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Bioengineering strategies for the fabrication of implantable lymphoid structures mimicking lymph nodes (LNs) and tertiary lymphoid structures (TLS) could amplify the adaptive immune response for therapeutic applications such as cancer immunotherapy. No method to date has resulted in the consistent formation of high endothelial venules (HEVs), which is the specialized vasculature responsible for naïve T cell recruitment and education in both LNs and TLS. Here orthogonal induced differentiation of human pluripotent stem cells carrying a regulatable ETV2 allele is used to rapidly and efficiently induce endothelial differentiation. Assembly of embryoid bodies combining primitive inducible endothelial cells and primary human LN fibroblastic reticular cells results in the formation of HEV-like structures that can aggregate into 3D organoids (HEVOs). Upon transplantation into immunodeficient mice, HEVOs successfully engraft and form lymphatic structures that recruit both antigen-presenting cells and adoptively-transferred lymphocytes, therefore displaying basic TLS capabilities. The results further show that functionally, HEVOs can organize an immune response and promote anti-tumor activity by adoptively-transferred T lymphocytes. Collectively, the experimental approaches represent an innovative and scalable proof-of-concept strategy for the fabrication of bioengineered TLS that can be deployed in vivo to enhance adaptive immune responses.
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Estruturas Linfoides Terciárias , Camundongos , Humanos , Animais , Estruturas Linfoides Terciárias/patologia , Vênulas , Células Endoteliais , Linfonodos , Organoides , Fatores de TranscriçãoRESUMO
Cerebrospinal fluid (CSF) leakage is a common complication of intradural surgery or incidental durotomy in neurosurgery. Dural suturing is a common method for durotomy repair, but this technique requires a long operation time and includes the risk of CSF leakage by incomplete sealing. Glue-type sealants are effective for watertight dural closure. However, unresolved shortcomings include insufficient sealing performance, poor biocompatibility, and excessive swelling. Here, a dural sealant using light-activated hyaluronic acid (HA) with multi-networks (HA photosealant) that provides fast sealing performance and high biocompatibility is reported. The HA photosealants form a watertight hydrogel barrier with multilength networks under low-energy visible light exposure (405 nm, <1 J cm-2) for 5 s and allow firm tissue adhesion on the wet dural surface. In a rabbit model of craniectomy and durotomy, HA photosealants exhibit the faster sealing performance of dural tears and enhance dural repair with accelerated bone formation compared to commercial surgical glues, with no degenerative changes, such as inflammation or necrosis, in histopathological evaluation. This biocompatible HA photosealant can be applied in a variety of clinical settings that require fast wound closure as a promising potential.
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Vazamento de Líquido Cefalorraquidiano , Ácido Hialurônico , Animais , Coelhos , Ácido Hialurônico/farmacologia , Procedimentos Neurocirúrgicos/métodos , Craniotomia , Hidrogéis/farmacologiaRESUMO
Engineered three-dimensional (3D) tissue constructs have emerged as a promising solution for regenerating damaged muscle tissue resulting from traumatic or surgical events. 3D architecture and function of the muscle tissue constructs can be customized by selecting types of biomaterials and cells that can be engineered with desired shapes and sizes through various nano- and micro-fabrication techniques. Despite significant progress in this field, further research is needed to improve, in terms of biomaterials properties and fabrication techniques, the resemblance of function and complex architecture of engineered constructs to native muscle tissues, potentially enhancing muscle tissue regeneration and restoring muscle function. In this review, we discuss the latest trends in using nano-biomaterials and advanced nano-/micro-fabrication techniques for creating 3D muscle tissue constructs and their regeneration ability. Current challenges and potential solutions are highlighted, and we discuss the implications and opportunities of a future perspective in the field, including the possibility for creating personalized and biomanufacturable platforms.
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Oxygenating biomaterials can alleviate anoxic stress, stimulate vascularization, and improve engraftment of cellularized implants. However, the effects of oxygen-generating materials on tissue formation have remained largely unknown. Here, we investigate the impact of calcium peroxide (CPO)-based oxygen-generating microparticles (OMPs) on the osteogenic fate of human mesenchymal stem cells (hMSCs) under a severely oxygen deficient microenvironment. To this end, CPO is microencapsulated in polycaprolactone to generate OMPs with prolonged oxygen release. Gelatin methacryloyl (GelMA) hydrogels containing osteogenesis-inducing silicate nanoparticles (SNP hydrogels), OMPs (OMP hydrogels), or both SNP and OMP (SNP/OMP hydrogels) are engineered to comparatively study their effect on the osteogenic fate of hMSCs. OMP hydrogels associate with improved osteogenic differentiation under both normoxic and anoxic conditions. Bulk mRNAseq analyses suggest that OMP hydrogels under anoxia regulate osteogenic differentiation pathways more strongly than SNP/OMP or SNP hydrogels under either anoxia or normoxia. Subcutaneous implantations reveal a stronger host cell invasion in SNP hydrogels, resulting in increased vasculogenesis. Furthermore, time-dependent expression of different osteogenic factors reveals progressive differentiation of hMSCs in OMP, SNP, and SNP/OMP hydrogels. Our work demonstrates that endowing hydrogels with OMPs can induce, improve, and steer the formation of functional engineered living tissues, which holds potential for numerous biomedical applications, including tissue regeneration and organ replacement therapy.
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Células-Tronco Mesenquimais , Osteogênese , Humanos , Diferenciação Celular , Engenharia Tecidual/métodos , Hidrogéis/farmacologia , Hipóxia/metabolismo , Oxigênio/metabolismoRESUMO
Injectable hydrogels based on natural polymers have shown great potential for various tissue engineering applications, such as wound healing. However, poor mechanical properties and weak self-healing ability are still major challenges. In this work, we introduce a host-guest (HG) supramolecular interaction between acrylate-ß-cyclodextrin (Ac-ß-CD) conjugated on methacrylated kappa-carrageenan (MA-κ-CA) and aromatic residues on gelatin to provide self-healing characteristics. We synthesize an MA-κ-CA to conjugate Ac-ß-CD and fabricate dual crosslinked hybrid hydrogels with gelatin to mimic the native extracellular matrix (ECM). The dual crosslinking occurs on the MA-κ-CA backbone through the addition of KCl and photocrosslinking process, which enhances mechanical strength and stability. The hybrid hydrogels exhibit shear-thinning, self-healing, and injectable behavior, which apply easily under a minimally invasive manner and contribute to shear stress during the injection. In-vitro studies indicate enhanced cell viability. Furthermore, scratch assays are performed to examine cell migration and cell-cell interaction. It is envisioned that the combination of self-healing and injectable dual crosslinked hybrid hydrogels with HG interactions display a promising and functional biomaterial platform for wound healing applications.
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Gelatina , Hidrogéis , Carragenina/farmacologia , Carragenina/química , Hidrogéis/farmacologia , Hidrogéis/química , Gelatina/farmacologia , Gelatina/química , Cicatrização , Materiais Biocompatíveis/químicaRESUMO
Scaffolds are implants commonly used to deliver cells, drugs, and genes into the body. Their regular porous structure ensures the proper support for cell attachment, proliferation, differentiated function, and migration. Techniques to fabricate a scaffold include leaching, freeze-drying, supercritical fluid technology, thermally induced phase separation, rapid prototyping, powder compaction, sol-gel, and melt molding. Gene delivery from the scaffold represents a versatile approach to influence the environment for managing cell function. Scaffolds can be used for various tissue engineering purposes, e.g. bone formation, periodontal regeneration, cartilage development, artificial corneas, heart valves, tendon repair, or ligament replacement. Moreover, they are also instrumental in cancer therapy, inflammation, diabetes, heart disease, and wound dressings. Scaffolds provide a platform to extend the delivery of drugs and genetic materials at a controlled timeframe, besides potentially being used to prevent infection upon surgery and other chronic diseases, provided that they can be formulated with specific medicines. This review discusses the need to design advanced functional scaffolds with the potential for modified drug delivery and tissue engineering in a synergistic approach. Special attention is given to works published in 2023 to generate the bibliometric map.
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Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , OsteogêneseRESUMO
Human cortical organoids (hCOs), derived from human induced pluripotent stem cells (iPSCs), provide a platform to interrogate mechanisms of human brain development and diseases in complex three- dimensional tissues. However, current hCO development methods lack important non-neural tissues, such as the surrounding meningeal layer, that have been shown to be essential for normal corticogenesis and brain development. Here, we first generated hCOs from a single rosette to create more homogenous organoids with consistent size around 250 µm by day 5. We then took advantage of a 3D co-culture system to encapsulate brain organoids with a thin layer of meningeal cells from the very early stages of cortical development. Immunostaining analysis was performed to display different cortical layer markers during different stages of development. Real-time monitoring of organoid development using IncuCyte displayed enhanced morphology and increased growth rate over time. We found that meningeal-encapsulated organoids illustrated better laminar organization by exhibiting higher expression of REELIN by Cajal-Retzius neurons. Presence of meningeal cells resulted in a greater expansion of TBR2 intermediate progenitor cells (IPCs), the deep cortical layer (CTIP2) and upper cortical layer (BRN2). Finally, meningeal-encapsulated organoids enhanced outer radial glial and astrocyte formation illustrated by stronger expression of HOPX and GFAP markers, respectively. This study presents a novel 3D co-culture platform to more closely mimic the in vivo cortical brain structure and enable us to better investigating mechanisms underlying the neurodevelopmental disorders during embryonic development.
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Células-Tronco Pluripotentes Induzidas , Humanos , Técnicas de Cocultura , Encéfalo , Neurônios/metabolismo , Organoides/metabolismoRESUMO
Chronic wounds in diabetic patients are challenging because their prolonged inflammation makes healing difficult, thus burdening patients, society, and health care systems. Customized dressing materials are needed to effectively treat such wounds that vary in shape and depth. The continuous development of 3D-printing technology along with artificial intelligence has increased the precision, versatility, and compatibility of various materials, thus providing the considerable potential to meet the abovementioned needs. Herein, functional 3D-printing inks comprising DNA from salmon sperm and DNA-induced biosilica inspired by marine sponges, are developed for the machine learning-based 3D-printing of wound dressings. The DNA and biomineralized silica are incorporated into hydrogel inks in a fast, facile manner. The 3D-printed wound dressing thus generates provided appropriate porosity, characterized by effective exudate and blood absorption at wound sites, and mechanical tunability indicated by good shape fidelity and printability during optimized 3D printing. Moreover, the DNA and biomineralized silica act as nanotherapeutics, enhancing the biological activity of the dressings in terms of reactive oxygen species scavenging, angiogenesis, and anti-inflammation activity, thereby accelerating acute and diabetic wound healing. These bioinspired 3D-printed hydrogels produce using a DNA-induced biomineralization strategy are an excellent functional platform for clinical applications in acute and chronic wound repair.
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Diabetes Mellitus , Hidrogéis , Masculino , Humanos , Hidrogéis/farmacologia , Inteligência Artificial , Biomineralização , Sêmen , Cicatrização , Impressão TridimensionalRESUMO
Developing bioelectronics that retains their long-term functionalities in the human body during daily activities is a current critical issue. To accomplish this, robust tissue adaptability and biointerfacing of bioelectronics should be achieved. Hydrogels have emerged as promising materials for bioelectronics that can softly adapt to and interface with tissues. However, hydrogels lack toughness, requisite electrical properties, and fabrication methodologies. Additionally, the water-swellable property of hydrogels weakens their mechanical properties. In this work, an intrinsically nonswellable multifunctional hydrogel exhibiting tissue-like moduli ranging from 10 to 100 kPa, toughness (400-873 J m-3 ), stretchability (≈1000% strain), and rapid self-healing ability (within 5 min), is developed. The incorporation of carboxyl- and hydroxyl-functionalized carbon nanotubes (fCNTs) ensures high conductivity of the hydrogel (≈40 S m-1 ), which can be maintained and recovered even after stretching or rupture. After a simple chemical modification, the hydrogel shows tissue-adhesive properties (≈50 kPa) against the target tissues. Moreover, the hydrogel can be 3D printed with a high resolution (≈100 µm) through heat treatment owing to its shear-thinning capacity, endowing it with fabrication versatility. The hydrogel is successfully applied to underwater electromyography (EMG) detection and ex vivo bladder expansion monitoring, demonstrating its potential for practical bioelectronics.
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Hidrogéis , Nanotubos de Carbono , Humanos , Hidrogéis/química , Nanotubos de Carbono/química , Condutividade ElétricaRESUMO
Heart disease is the leading cause of death worldwide and imposes a significant burden on healthcare systems globally. A major hurdle to the development of more effective therapeutics is the reliance on animal models that fail to faithfully recapitulate human pathophysiology. The predictivity of in vitro models that lack the complexity of in vivo tissue remain poor as well. To combat these issues, researchers are developing organ-on-a-chip models of the heart that leverage the use of human induced pluripotent stem cell-derived cardiomyocytes in combination with novel platforms engineered to better recapitulate tissue- and organ-level physiology. The integration of novel biosensors into these platforms is also a critical step in the development of these models, as they allow for increased throughput, real-time and longitudinal phenotypic assessment, and improved efficiency during preclinical disease modeling and drug screening studies. These platforms hold great promise for both improving our understanding of heart disease as well as for screening potential therapeutics based on clinically relevant endpoints with better predictivity of clinical outcomes. In this review, we describe state-of-the-art heart-on-a-chip platforms, the integration of novel biosensors into these models for real-time and continual monitoring of tissue-level physiology, as well as their use for modeling heart disease and drug screening applications. We also discuss future perspectives and further advances required to enable clinical trials-on-a-chip and next-generation precision medicine platforms.