RESUMEN
Wearable pressure sensors have become increasingly popular for personal healthcare and motion detection applications due to recent advances in materials science and functional nanomaterials. In this study, a novel composite hydrogel is presented as a sensitive piezoresistive sensor that can be utilized for various biomedical applications, such as wearable skin patches and integrated artificial skin that can measure pulse and blood pressure, as well as monitor sound as a self-powered microphone. The hydrogel is composed of self-assembled short peptides containing aromatic, positively- or negatively charged amino acids combined with 2D Ti3C2Tz MXene nanosheets. This material is low-cost, facile, reliable, and scalable for large areas while maintaining high sensitivity, a wide detection range, durability, oxidation stability, and biocompatibility. The bioinspired nanostructure, strong mechanical stability, and ease of functionalization make the assembled peptide-based composite MXene-hydrogel a promising and widely applicable material for use in bio-related wearable electronics.
Asunto(s)
Hidrogeles , Péptidos , Dispositivos Electrónicos Vestibles , Péptidos/química , Hidrogeles/química , Humanos , Conductividad Eléctrica , Nanoestructuras/química , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentaciónRESUMEN
AIM: To investigate the potential of an ultrashort aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration. MATERIALS AND METHODS: Fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3-E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5-mm-diameter calvarial critical-sized defects were prepared in 20 Sprague-Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate hydrogel or left unfilled. Eight weeks after implantation, histology and micro-computed tomography analyses were performed. Immunohistochemistry was performed in six rats to assess the hydrogel's immunomodulatory effect. RESULTS: A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46 KPa was prepared. It supported osteogenic differentiation of MC3T3-E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum-hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone. CONCLUSIONS: FmocFF/HA hydrogel can serve as a cell-free, biomimetic, immunomodulatory scaffold for bone regeneration.
Asunto(s)
Ácido Hialurónico , Hidrogeles , Ratas , Animales , Bovinos , Hidrogeles/farmacología , Hidrogeles/química , Ácido Hialurónico/farmacología , Ácido Hialurónico/uso terapéutico , Osteogénesis , Microtomografía por Rayos X , Calcio/farmacología , Ratas Sprague-Dawley , Regeneración Ósea , Periostio , Andamios del Tejido/químicaRESUMEN
Over the last decade, three-dimensional (3D) printing technologies have attracted the interest of researchers due to the possibility of fabricating tissue- and organ-like structures with similarities to the organ of interest. One of the most widely used materials for the fabrication of bioinks is gelatin (Gel) due to its excellent biocompatibility properties. However, in order to fabricate stable scaffolds under physiological conditions, the most common approach is to use gelatin methacrylate (GelMA) that allows the crosslinking and therefore the stabilization of the hydrogel through UV crosslinking. The crosslinking process can be harmful to cells thus decreasing total cell viability. To overcome the need for post-printing crosslinking, a new approach of bioink formulation was studied, incorporating the Fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) peptide into the Gel bioink. However, although Fmoc-FF possesses excellent mechanical properties, the lack of elasticity and viscosity makes it unsuitable for 3D-printing. Here, we demonstrate that covalent conjugation of two different ethylene glycol (EG) motifs to the Fmoc-FF peptide increases the hydrophilicity and elasticity properties, which are essential for 3D-printing. This new approach for bioink formulation avoids the need for any post-printing manufacturing processes, such as chemical or UV crosslinking.
Asunto(s)
Glicol de Etileno , Gelatina , Dipéptidos , Etilenos , Fluorenos , Hidrogeles/química , Péptidos , Fenilalanina , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Engineering ordered nanostructures through molecular self-assembly of simple building blocks constitutes the essence of modern nanotechnology to develop functional supramolecular biomaterials. However, the lack of adequate chemical and functional diversity often hinders the utilization of unimolecular self-assemblies for practical applications. Co-assembly of two different building blocks can essentially harness both of their attributes and produce nanostructured macro-scale objects with improved physical properties and desired functional complexity. Herein, the authors report the co-operative co-assembly of a modified amino acid, fluorenylmethoxycarbonyl-pentafluoro-phenylalanine (Fmoc-F5 -Phe), and a peptide, Fmoc-Lys(Fmoc)-Arg-Gly-Asp [Fmoc-K(Fmoc)-RGD] into a functional supramolecular hydrogel. A change in the morphology and fluorescence emission, as well as improvement of the mechanical properties in the mixed hydrogels compared to the pristine hydrogels, demonstrate the signature of co-operative co-assembly mechanism. Intriguingly, this approach harnesses the advantages of both components in a synergistic way, resulting in a single homogeneous biomaterial possessing the antimicrobial property of Fmoc-F5 -Phe and the biocompatibility and cell adhesive characteristics of Fmoc-K(Fmoc)-RGD. This work exemplifies the importance of the co-assembly process in nanotechnology and lays the foundation for future developments in supramolecular chemistry by harnessing the advantages of diverse functional building blocks into a mechanically stable functional biomaterial.
Asunto(s)
Hidrogeles , Nanoestructuras , Aminoácidos/química , Materiales Biocompatibles , Hidrogeles/química , Nanoestructuras/química , Fenilalanina/químicaRESUMEN
Supramolecular hydrogels formed by the self-assembly of amino-acid based gelators are receiving increasing attention from the fields of biomedicine and material science. Self-assembled systems exhibit well-ordered functional architectures and unique physicochemical properties. However, the control over the kinetics and mechanical properties of the end-products remains puzzling. A minimal alteration of the chemical environment could cause a significant impact. In this context, we report the effects of modifying the position of a single atom on the properties and kinetics of the self-assembly process. A combination of experimental and computational methods, used to investigate double-fluorinated Fmoc-Phe derivatives, Fmoc-3,4F-Phe and Fmoc-3,5F-Phe, reveals the unique effects of modifying the position of a single fluorine on the self-assembly process, and the physical properties of the product. The presence of significant physical and morphological differences between the two derivatives was verified by molecular-dynamics simulations. Analysis of the spontaneous phase-transition of both building blocks, as well as crystal X-ray diffraction to determine the molecular structure of Fmoc-3,4F-Phe, are in good agreement with known changes in the Phe fluorination pattern and highlight the effect of a single atom position on the self-assembly process. These findings prove that fluorination is an effective strategy to influence supramolecular organization on the nanoscale. Moreover, we believe that a deep understanding of the self-assembly process may provide fundamental insights that will facilitate the development of optimal amino-acid-based low-molecular-weight hydrogelators for a wide range of applications.
Asunto(s)
Aminoácidos/química , Fluorenos/química , Halogenación , Simulación de Dinámica Molecular , Fenilalanina/química , Algoritmos , Hidrogeles/química , Cinética , Microscopía Electrónica de Transmisión , Estructura Molecular , Peso Molecular , Transición de Fase , Fenómenos Físicos , Reología , Difracción de Rayos XRESUMEN
Hyaluronic acid (HA), a major component of the extracellular matrix, is an attractive material for various medical applications. Yet, its low mechanical rigidity and fast in vivo degradation hinder its utilization. Here, we demonstrate the reinforcement of HA by its integration with a low-molecular-weight peptide hydrogelator to produce a composite hydrogel. The formulation of HA with the fluorenylmethoxycarbonyl diphenylalanine (FmocFF) peptide, one of the most studied self-assembling hydrogel-forming building blocks, showing notable mechanical properties, resulted in the formation of stable, homogeneous hydrogels. Electron microscopy analysis demonstrated a uniform distribution of the two matrices in the composite forms. The composite hydrogels showed improved mechanical properties and stability to enzymatic degradation while maintaining their biocompatibility. Moreover, the storage modulus of the FmocFF/HA composite hydrogels reached up to 25 kPa. The composite hydrogels allowed sustained release of curcumin, a hydrophobic polyphenol showing antioxidant, anti-inflammatory, and antitumor activities. Importantly, the rate of curcumin release was modulated as a function of the concentration of the FmocFF peptide within the hydrogel matrix. This work provides a new approach for conferring mechanical rigidity and stability to HA without the need of cross-linking, thus potentially facilitating its utilization in different clinical applications, such as sustained drug release.
Asunto(s)
Materiales Biocompatibles/química , Matriz Extracelular/química , Ácido Hialurónico/química , Hidrogeles/química , Péptidos/química , Materiales Biocompatibles/síntesis química , Péptidos/síntesis químicaRESUMEN
The familial disease of hereditary multiple exostoses is characterized by abnormal skeletal deformities requiring extensive surgical procedures. In hereditary multiple exostoses patients there is a shortage in the pericellular glycosaminoglycan (GAG) of heparan sulfate (HS), related to defective activity of HS glycosyltransferases, mainly in the pericellular regions of chondrocytes. This study searched for a novel approach employing xylosides with different aglycone groups priming a variety of GAG chains, in attempting to alter the GAG compositional profile. Cell cultures of patients with osteochondroma responded to p-nitrophenyl ß-D-xyloside by a significant increase in total GAG synthesis, expressed mainly in the extracellular domains, limited to chondroitin sulfate). The different ß-D-xylosides, in addition to increasing the synthesis of extracellular GAGs, led to a significant depletion of the intracellular GAG domains. In mouse chondrocyte cultures, ß-D-xylosides with different aglycones created a unique distribution of the GAG pools. Of special interest was the finding that the naphthalene methanol ß-D-xyloside showed the highest absolute levels of HS-GAGs in both extracellular and intra-pericellular moieties compared with other ß-D-xylosides and with controls without xyloside. In summary, ß-D-xylosides can be utilized in chondrocyte cultures to modify the distribution of GAGs between the extracellular and intracellular compartments. In addition, xylosides may alter the profile of specific GAG chains in each moiety.
Asunto(s)
Condrocitos/efectos de los fármacos , Sulfatos de Condroitina/biosíntesis , Glicósidos/farmacología , Animales , Animales Recién Nacidos , Línea Celular , Condrocitos/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Ratones , Naftalenos/farmacología , Osteocondroma , Células Tumorales CultivadasRESUMEN
A simple, linear polysaccharide with unique molecular functions, hyaluronan is a glycosaminoglycan whose biomechanical and hydrodynamic properties have been thoroughly characterized. However, the exact role the molecular mechanisms and signaling pathways of hyaluronan play in the regulation of stem cell fate, such as self-renewal and differentiation, remains to be determined. The abundance of hyaluronan in embryonic tissues indicates that it is highly important in developmental processes. Recent studies have focused on understanding the mechanisms of hydrated hyaluronan action and its interaction with neighboring substances. This review is an attempt to elucidate the complex role of hyaluronan signaling in the initialization and regulation of developmental processes, particularly in events dictating the fates of mesenchymal stem cells during the organogenetic phases of chondrogenesis and osteogenesis.
Asunto(s)
Condrogénesis/fisiología , Ácido Hialurónico/fisiología , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/fisiología , Animales , Cartílago/metabolismo , Diferenciación Celular/fisiología , Transición Epitelial-Mesenquimal/fisiología , Extremidades/embriología , Humanos , Receptores de Hialuranos/fisiología , Articulaciones/embriología , Células Madre Mesenquimatosas/citología , Transducción de Señal/fisiologíaRESUMEN
Stem cell development and fate decisions are dictated by the microenvironment in which the stem cell is embedded. Among the advanced goals of tissue engineering is the creation of a microenvironment that will support the maintenance and differentiation of the stem cell--based on embryonic and adult stem cells as potent, cellular sources--for a variety of clinical applications. This review discusses some of the approaches used to create regulatory and instructive microenvironments for the directed differentiation of mesenchymal stem cells (MSCs) using three-dimensional crystalline calcium carbonate biomaterials of marine origin combined with a hydrated gel based on hyaluronan.
Asunto(s)
Carbonato de Calcio , Ácido Hialurónico , Células Madre/citología , Ingeniería de Tejidos/métodos , Animales , Antozoos , Materiales Biocompatibles , Conformación de Carbohidratos , Diferenciación Celular , Hidrogeles , Células Madre/fisiologíaRESUMEN
Adhesion of bacteria to biomaterials and the ability of many microorganisms to form biofilms on foreign bodies are well-established as major contributors to the pathogenesis of implant-associated infections. Treatment of bone infection remains problematic, due to the difficulty of systemically administered antibiotics to locally penetrate bone. The current research addresses this issue by focusing on the development and study of novel gentamicin-loaded bioresorbable films designed to serve as "coatings" for fracture fixation devices and prevent implant-associated infections. Poly(L-lactic acid) and poly (D,L-lactic-co-glycolic acid) films containing gentamicin were developed through solution processing. The effects of polymer type, drug content, and processing conditions on the drug release profile were studied with respect to film morphology. The examined films generally exhibited a burst effect followed by a moderate approximately constant rate of release. The drug contents in the surrounding medium exceeded the required minimal effective concentration. Various gentamicin concentrations that were released from the films with time exhibited efficacy against bacterial species known to be involved in orthopedic infections. The developed systems can be applied on the surface of any metallic or polymeric fracture fixation device, and may therefore comprise a significant contribution to the field of orthopedic implants.
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Antibacterianos/metabolismo , Infecciones Bacterianas/prevención & control , Biopelículas , Gentamicinas/metabolismo , Equipo Ortopédico/microbiología , Prótesis e Implantes/microbiología , Infecciones Relacionadas con Prótesis/prevención & control , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Recuento de Colonia Microbiana , Gentamicinas/farmacología , Glicolatos/metabolismo , Ácido Láctico/metabolismo , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Peso Molecular , Poliésteres , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/metabolismo , Factores de TiempoRESUMEN
Adipogenic and osteogenic cells share part of the early differentiation cascade of mesenchymal stem cells (MSCs). The choice of a mesenchymal precursor cell to differentiate into a particular cell type is dictated by many spatial and temporal cues, including growth factors, neighboring mature cells, and the extracellular matrix (ECM), which plays an important role in bone formation. Whether adipocytes that have initiated differentiation along one lineage can convert into osteogenic lineage by merely interacting with materials having specific surface parameters is unknown. Using crystalline three-dimensional (3D) biomatrices of marine origin (CaCO(3)), we explored whether preadipocytes can convert into osteoblasts. Cells (3T3F442A) were seeded on 3D biomatrices of marine origin (Porites lutea). Analyses were made at different time intervals-1, 2, 5, 7, 14, 21, and 28 days post-seeding. Cell characterizations were done using morphological (light microscopy and scanning electron microscopy), histological (Alizarin red, von Kossa and Oil red O staining), enzymatic (alkaline phosphatase activity, and quantitative PCR testing transcript levels of osteocalcin, alkaline phosphatase, core binding factor- 1 (Cbfa1), and fatty acid binding protein (aP2). We demonstrated 3T3F442A preadipocyte modulation and differentiation into bone-forming cells when grown on biomatrix of marine origin without addition of other bone morphogenesis inducers. We found an active ossification process typical of osteogenic phenotype as early as 2 days after seeding. It is suggested that this crystalline biomatrix having a particular 3D topology or surface parameters supports fast cellular adhesion, proliferation, and differentiation of preadipocytes to osteogenic phenotype.