RESUMEN
The lack of both digital light processing (DLP) compatible and biocompatible photopolymers, along with inappropriate material properties required for wearable sensor applications, substantially hinders the employment of DLP 3D printing in the fabrication of multifunctional hydrogels. Herein, we discovered and implemented a photoreactive poloxamer derivative, Pluronic F-127 diacrylate, which overcomes these limitations and is optimized to achieve DLP 3D printed micelle-based hydrogels with high structural complexity, resolution, and precision. In addition, the dehydrated hydrogels exhibit a shape-memory effect and are conformally attached to the geometry of the detection point after rehydration, which implies the 4D printing characteristic of the fabrication process and is beneficial for the storage and application of the device. The excellent cytocompatibility and in vivo biocompatibility further strengthen the potential application of the poloxamer micelle-based hydrogels as a platform for multifunctional wearable systems. After processing them with a lithium chloride (LiCl) solution, multifunctional conductive ionic hydrogels with antifreezing and antiswelling properties along with good transparency and water retention are easily prepared. As capacitive flexible sensors, the DLP 3D printed micelle-based hydrogel devices exhibit excellent sensitivity, cycling stability, and durability in detecting multimodal deformations. Moreover, the DLP 3D printed conductive hydrogels are successfully applied as real-time human motion and tactile sensors with satisfactory sensing performances even in a -20 °C low-temperature environment.
Asunto(s)
Micelas , Dispositivos Electrónicos Vestibles , Humanos , Poloxámero , Conductividad Eléctrica , Hidrogeles , Impresión TridimensionalRESUMEN
As one of the long-established and necessary medical devices, surgical sutures play an essentially important role in the closing and healing of damaged tissues and organs postoperatively. The recent advances in multiple disciplines, like materials science, engineering technology, and biomedicine, have facilitated the generation of various innovative surgical sutures with humanization and multi-functionalization. For instance, the application of numerous absorbable materials is assuredly a marvelous progression in terms of surgical sutures. Moreover, some fantastic results from recent laboratory research cannot be ignored either, ranging from the fiber generation to the suture structure, as well as the suture modification, functionalization, and even intellectualization. In this review, the suture materials, including natural or synthetic polymers, absorbable or non-absorbable polymers, and metal materials, were first introduced, and then their advantages and disadvantages were summarized. Then we introduced and discussed various fiber fabrication strategies for the production of surgical sutures. Noticeably, advanced nanofiber generation strategies were highlighted. This review further summarized a wide and diverse variety of suture structures and further discussed their different features. After that, we covered the advanced design and development of surgical sutures with multiple functionalizations, which mainly included surface coating technologies and direct drug-loading technologies. Meanwhile, the review highlighted some smart and intelligent sutures that can monitor the wound status in a real-time manner and provide on-demand therapies accordingly. Furthermore, some representative commercial sutures were also introduced and summarized. At the end of this review, we discussed the challenges and future prospects in the field of surgical sutures in depth. This review aims to provide a meaningful reference and guidance for the future design and fabrication of innovative surgical sutures. STATEMENT OF SIGNIFICANCE: This review article introduces the recent advances of surgical sutures, including material selection, fiber morphology, suture structure and construction, as well as suture modification, functionalization, and even intellectualization. Importantly, some innovative strategies for the construction of multifunctional sutures with predetermined biological properties are highlighted. Moreover, some important commercial suture products are systematically summarized and compared. This review also discusses the challenges and future prospects of advanced sutures in a deep manner. In all, this review is expected to arouse great interest from a broad group of readers in the fields of multifunctional biomaterials and regenerative medicine.
Asunto(s)
Materiales Biocompatibles , Medicina Regenerativa , Materiales Biocompatibles/química , Cicatrización de Heridas , Suturas , Polímeros/química , Técnicas de SuturaRESUMEN
The stellate ganglion (SG) is a part of the sympathetic nervous system that has important regulatory effects on several human tissues and organs in the upper body. SG block and intervention have been clinically and preclinically implemented to manage chronic pain in the upper extremities, neck, head, and upper chest as well as chronic heart failure. However, there has been very limited effort to develop and investigate polymer-based drug delivery systems for local delivery to the SG. In this study, we fabricated red blood cell (RBC) membrane-camouflaged poly(lactic-co-glycolic acid) (PLGA) (PLGAM) microparticles for use as a potential long-term controlled release system for local drug delivery. The structure, size, and surface zeta potential results indicated that the spherical PLGAM microparticles were successfully fabricated. Both PLGA and PLGAM microparticles exhibited biocompatibility with human adipose mesenchymal stem cells (ADMSC) and satellite glial cells and showed hemocompatibility. In addition, both PLGA and PLGAM displayed no significant effects on the secretion of proinflammatory cytokines by human monocyte derived macrophages in vitro. We microinjected microparticles into rat SGs and evaluated the retention time of microparticles and the effects of the microparticles on inflammation in vivo over 21 days. Subsequently, we fabricated drug-loaded PLGAM microparticles by using GW2580, a colony stimulating factor-1 receptor inhibitor, as a model drug and assessed its encapsulation efficiency, drug release profiles, biocompatibility, and anti-inflammatory effects in vitro. Our results demonstrated the potential of PLGAM microparticles for long-term controlled local drug release in the SG. STATEMENT OF SIGNIFICANCE: SG block by locally injecting therapeutics to inhibit the activity of the sympathetic nerves provides a valuable benefit to manage chronic pain and chronic heart failure. We describe the fabrication of RBC membrane-camouflaged PLGA microparticles with cytocompatibility, hemocompatibility, and low immunogenicity, and demonstrate that they can be successfully and safely microinjected into rat SGs. The microparticle retention time within SG is over 21 days without eliciting detectable inflammation. Furthermore, we incorporate a CSF-1R inhibitor as a model drug and demonstrate the capacities of long-term drug release and regulation of macrophage functions. The strategies demonstrate the feasibility to locally microinject therapeutics loaded microparticles into SGs and pave the way for further efficacy and disease treatment evaluation.
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Dolor Crónico , Ácido Poliglicólico , Ratas , Humanos , Animales , Preparaciones de Acción Retardada/farmacología , Preparaciones de Acción Retardada/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Poliglicólico/química , Glicoles , Ácido Láctico/química , Microinyecciones , Ganglio Estrellado , Sistemas de Liberación de Medicamentos/métodos , Inflamación , EritrocitosRESUMEN
Postoperative abdominal adhesions are a common problem after surgery and can produce serious complications. Current antiadhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable cream-like hydrogels with multiple functionalities, including rapid gelation, self-healing, antioxidation, anti-inflammation, and anti-cell adhesion. The multifunctional hydrogels were facilely formed by the conjugation reaction of epigallocatechin-3-gallate (EGCG) and hyaluronic acid (HA)-based microgels and poly(vinyl alcohol) (PVA) based on the dynamic boronic ester bond. The physicochemical properties of the hydrogels including antioxidative and anti-inflammatory activities were systematically characterized. A mouse cecum-abdominal wall adhesion model was implemented to investigate the efficacy of our microgel-based hydrogels in preventing postoperative abdominal adhesions. The hydrogels, with a high molecular weight HA, significantly decreased the inflammation, oxidative stress, and fibrosis and reduced the abdominal adhesion formation, compared to the commercial Seprafilm group or Injury-only group. Label-free quantitative proteomics analysis demonstrated that S100A8 and S100A9 expressions were associated with adhesion formation; the microgel-containing hydrogels inhibited these expressions. The microgel-containing hydrogels with multifunctionality decreased the formation of postoperative intra-abdominal adhesions in a murine model, demonstrating promise for clinical applications.
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Pared Abdominal , Microgeles , Ratones , Animales , Hidrogeles/química , Pared Abdominal/patología , Pared Abdominal/cirugía , Adherencias Tisulares/prevención & control , Adherencias Tisulares/patología , Inflamación/patologíaRESUMEN
Due to their intrinsic injectable and self-healing characteristics, dynamic hydrogels, based on dynamic covalent bonds, have gained a great attention. In this study, a novel dynamic hydrogel based on the boronic ester dynamic covalent bond is facilely developed using phenylboronic acid-modified hyaluronic acid (HA-PBA) and plant-derived polyphenol-tannic acid (TA). The dynamic hydrogel gelated quickly under mild conditions and had favorable viscoelastic properties with good self-healing and shear-thinning capabilities. Moreover, the simultaneous utilization of TA as a reductant for the green synthesis of silver nanoparticles (AgNP) inspired the preparation of a TA-reduced AgNP hybrid dynamic hydrogel with potent and broad-spectrum antibacterial activities. The dynamic hydrogels could also be applied for pH- and reactive oxygen species (ROS)-responsive release of loaded protein molecules without showing evident cytotoxicity and hemolysis in vitro. In addition, the dynamic hydrogels showed the anti-oxidative properties of high free radical and ROS scavenging capacity, which was verified by the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical assay and ROS fluorescence staining. Overall, this novel class of cytocompatible, self-healing, dual stimuli responsive, antibacterial, anti-oxidative, and injectable hydrogels could be promising as a wound dressing for chronic wound healing.
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Antibacterianos/farmacología , Antioxidantes/farmacología , Materiales Biocompatibles/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Taninos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antioxidantes/síntesis química , Antioxidantes/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Compuestos de Bifenilo/antagonistas & inhibidores , Ácidos Borónicos/química , Ácidos Borónicos/farmacología , Células Cultivadas , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Hidrogeles/síntesis química , Hidrogeles/química , Hidrogeles/farmacología , Ensayo de Materiales , Ratones , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Tamaño de la Partícula , Picratos/antagonistas & inhibidores , Polifenoles/química , Polifenoles/farmacología , Taninos/químicaRESUMEN
Electrostatic flocking, a textile engineering technique, uses Coulombic driving forces to propel conductive microfibers toward an adhesive-coated substrate, leaving a forest of aligned fibers. Though an easy way to induce anisotropy along a surface, this technique is limited to microfibers capable of accumulating charge. This study reports a novel method, utilizing principles from the percolation theory to make electrically insulative polymeric microfibers flockable. A variety of well-mixed, conductive materials are added to multiple insulative and biodegradable polymer microfibers during wet spinning, which enables nearly all types of polymer microfibers to accumulate sufficient charges required for flocking. Biphasic, biodegradable scaffolds are fabricated by flocking silver nanoparticle (AgNP)-filled poly(ε-caprolactone) (PCL) microfibers onto substrates made from 3D printing, electrospinning, and thin-film casting. The incorporation of AgNP into PCL fibers and use of chitosan-based adhesive enables antimicrobial activity against methicillin-resistant Staphylococcus aureus. The fabricated scaffolds demonstrate both favorable in vitro cell response and new tissue formation after subcutaneous implantation in rats, as evident by newly formed blood vessels and infiltrated cells. This technology opens the door for using previously unflockable polymer microfibers as surface modifiers or standalone structures in various engineering fields.
Asunto(s)
Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Animales , Poliésteres , Polímeros , Ratas , Plata , Electricidad Estática , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Functional reconstruction of craniomaxillofacial defects is challenging, especially for the patients who suffer from traumatic injury, cranioplasty, and oncologic surgery. Three-dimensional (3D) printing/bioprinting technologies provide a promising tool to fabricate bone tissue engineering constructs with complex architectures and bioactive components. In this study, we implemented multi-material 3D printing to fabricate 3D printed PCL/hydrogel composite scaffolds loaded with dual bioactive small molecules (i.e. resveratrol and strontium ranelate). The incorporated small molecules are expected to target several types of bone cells. We systematically studied the scaffold morphologies and small molecule release profiles. We then investigated the effects of the released small molecules from the drug loaded scaffolds on the behavior and differentiation of mesenchymal stem cells (MSCs), monocyte-derived osteoclasts, and endothelial cells. The 3D printed scaffolds, with and without small molecules, were further implanted into a rat model with a critical-sized mandibular bone defect. We found that the bone scaffolds containing the dual small molecules had combinational advantages in enhancing angiogenesis and inhibiting osteoclast activities, and they synergistically promoted MSC osteogenic differentiation. The dual drug loaded scaffolds also significantly promoted in vivo mandibular bone formation after 8 week implantation. This work presents a 3D printing strategy to fabricate engineered bone constructs, which can likely be used as off-the-shelf products to promote craniomaxillofacial regeneration.
Asunto(s)
Regeneración Ósea/efectos de los fármacos , Mandíbula/fisiología , Impresión Tridimensional , Bibliotecas de Moléculas Pequeñas/administración & dosificación , Bibliotecas de Moléculas Pequeñas/farmacología , Andamios del Tejido/química , Animales , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Mandíbula/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Monocitos/citología , Monocitos/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
Vascularization is a fundamental prerequisite for large bone construct development and remains one of the main challenges of bone tissue engineering. Our current study presents the combination of 3D printing technique with a hydrogel-based prevascularization strategy to generate prevascularized bone constructs. Human adipose derived mesenchymal stem cells (ADMSC) and human umbilical vein endothelial cells (HUVEC) were encapsulated within our bioactive hydrogels, and the effects of culture conditions on in vitro vascularization were determined. We further generated composite constructs by forming 3D printed polycaprolactone/hydroxyapatite scaffolds coated with cell-laden hydrogels and determined how the co-culture affected vascularization and osteogenesis. It was demonstrated that 3D co-cultured ADMSC-HUVEC generated capillary-like networks within the porous 3D printed scaffold. The co-culture systems promoted in vitro vascularization, but had no significant effects on osteogenesis. The prevascularized constructs were subcutaneously implanted into nude mice to evaluate the in vivo vascularization capacity and the functionality of engineered vessels. The hydrogel systems facilitated microvessel and lumen formation and promoted anastomosis of vascular networks of human origin with host murine vasculature. These findings demonstrate the potential of prevascularized 3D printed scaffolds with anatomical shape for the healing of larger bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1788-1798, 2018.