RESUMEN
Human civilization has witnessed the use of materials-derived from biomolecules of plants and animal origin for biomedical applications since ancient era. In recent years, precision design principles have been adopted to develop novel biomaterials derived from biomolecules. The biomolecules-derived biomaterials fabrication is dependent on chemical, biochemical and mechanical parameters of biomolecules and their bulk materials. Thus, structural variations and weak noncovalent interactions present within the basic building blocks greatly influence the functional features and applications. This comprehensive review provides one-stop information on recent innovations of various biomaterial-types derived from a diverse class of biomolecules through selected and representative examples with potential biomedical applications ranging from diagnosis, biosensing, antimicrobial efficacy, anticancer therapeutics, drug delivery, bioprinting, bioimaging, tissue engineering and regenerative medicine. The discussion systematically follows the top-down approach in the order of molecular complexity viz., biomacromolecules, oligomers and monomers of all classes of biomolecules (proteins, nucleic acids, carbohydrates and lipids) including a special section on biohybrid materials derived from molecular systems integrated with more than one class of biomolecules. In addition to providing overview of impressive advancements in the area, synergistic integration of biomolecules with synthetic materials to develop smart biomaterials is emphasized to improve the chemical, mechanical, stimuli-responsiveness, immunogenicity and biocompatibility features.
Asunto(s)
Bioimpresión , Ácidos Nucleicos , Animales , Materiales Biocompatibles , Humanos , Medicina Regenerativa , Ingeniería de TejidosRESUMEN
Nerve restoration and repair in the central nervous system is complicated and requires several factors to be considered while designing the scaffolds like being bioactive as well as having neuroinductive, neuroconductive and antioxidant properties. Aligned electrospun nanofibers provide necessary guidance and topographical cues required for directing the axonal and neurite outgrowth during regeneration. Conduction of nerve impulses is a mandatory feature of a typical nerve. The neuro-conductive property can be imparted by blending the biodegradable, bioactive polymers with conductive polymers. This will provide additional features, i.e., electrical cues to the already existing topographical and bioactive cues in order to make it a more multifaceted neuroregenerative approach. Hence in the present study, we used a combination of silk fibroin and melanin for the fabrication of random and aligned electrospun nanofibrous composite scaffolds. We performed the physico-chemical characterization and also assessed their antioxidant properties. We also evaluated their neurogenic potential using human neuroblastoma cells (SH-SY5Y) for their cellular viability, proliferation, adhesion and differentiation levels. Designed nanofibrous scaffolds had adequate physical properties suitable as neural substrates to promote neuronal growth and regeneration. They stimulated the neuroblastoma cell attachment and viability indicating their biocompatible nature. Silk/melanin composite scaffolds have specifically exhibited high antioxidant nature proven by the radical scavenging activity. Additionally, the melanin incorporated aligned silk fibroin scaffolds promoted the cell differentiation into neurons and orientation along their axis. Our results confirmed the potential of melanin incorporated aligned silk fibroin scaffolds as the promising candidates for effective nerve regeneration and recovery.
Asunto(s)
Antioxidantes/farmacología , Electricidad , Fibroínas/química , Melaninas/farmacología , Nanofibras/química , Tejido Nervioso/fisiología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Animales , Bombyx , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Nanofibras/ultraestructura , Tejido Nervioso/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , TermogravimetríaRESUMEN
Ambidextrous supergelators are developed through structure-gelation screening of rationally designed cyclic dipeptides (CDPs). The organo- and hydrogels of CDPs were thoroughly characterized by their minimal gelation concentration (MGC) for organic and aqueous solvents, thermal stability (Tg), and viscoelastic properties. Intermolecular hydrogen bonding, the major driving force for gelation was evaluated using temperature-dependent nuclear magnetic resonance (NMR) spectroscopy. The contribution of attractive van der Waals interaction of tBoc group in driving CDP gelation was ascertained using ß-cyclodextrin (ß-CD)-adamantane carboxylic acid (AC)-based host-guest gelation and 1H NMR studies. The self-assembled fibrous network of CDPs in organic and aqueous solvents responsible for the molecular gelation was elucidated using field emission scanning electron microscopy (FESEM) analysis. Among the CDPs studied CDP-2 found to be supergelator with MGC of 0.3 wt % and form in situ hydrogels under simulated physiological conditions. The in situ gelation property was evaluated by the incorporation of curcumin, as a model study to demonstrate the drug delivery application. Furthermore, supergelator CDP-2 was found to exhibit in cellulo cytocompatibility. Moreover, density functional theory (DFT) calculations were carried out to propose the microscopic structure for the self-assembly of CDP compounds and intermolecular N-H···O hydrogen bonding interactions appear to stabilize the fibrous network. The hydrophobic interactions among the tert-butyloxycarbonyl (tBoc) groups and π-π stacking interactions between phenyl rings contribute to the further stabilization of self-assembled 2D fibrous networks of CDPs. Overall, the present study highlights the in situ gelation property of CDP-based supergelators and their potential for biomedical and regenerative medicine applications.
Asunto(s)
Dipéptidos/química , Hidrogeles/química , Solventes/química , Dicroismo Circular , Dipéptidos/síntesis química , Hidrogeles/síntesis química , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía de Fuerza Atómica , Agua/químicaRESUMEN
Cyclic dipeptides (CDPs) are heterocyclic 2,5-diketopiperazines with exceptional structural rigidity, enzymatic stability, and biological activity, exhibiting a substantial tendency to take part in intermolecular interactions. Strong intermolecular interactions driven by unique hydrogen bonding patterns render CDPs with a high propensity to undergo molecular self-assembly. In this Review, the aim is to provide a comprehensive summary of design strategies used to engineer the molecular self-assembly of CDPs into functional nano- and micro-architectures and molecular gels with potential applications in biomedical and materials engineering fields.
RESUMEN
Surface interactions at the biomaterial-cellular interface determine the proliferation and differentiation of stem cells. Manipulating such interactions through the surface chemistry of scaffolds renders control over directed stem cell differentiation into the cell lineage of interest. This approach is of central importance for stem cell-based tissue engineering and regenerative therapy applications. In the present study, silk fibroin films (SFFs) decorated with integrin-binding laminin peptide motifs (YIGSR and GYIGSR) were prepared and employed for in vitro adult stem cell-based neural tissue engineering applications. Functionalization of SFFs with short peptides showcased the peptide sequence and nature of functionalization-dependent differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs). Intriguingly, covalently functionalized SFFs with GYIGSR hexapeptide (CL2-SFF) supported hMSC proliferation and maintenance in an undifferentiated pluripotent state and directed the differentiation of hMSCs into neuron-like cells in the presence of a biochemical cue, on-demand. The observed morphological changes were further corroborated by the up-regulation of neuronal-specific marker gene expression (MAP2, TUBB3, NEFL), confirmed through semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. The enhanced proliferation and on-demand directed differentiation of adult stem cells (hMSCs) by the use of an economically viable short recognition peptide (GYIGSR), as opposed to the integrin recognition protein laminin, establishes the potential of SFFs for neural tissue engineering and regenerative therapy applications.
Asunto(s)
Células Madre Mesenquimatosas , Diferenciación Celular , Proliferación Celular , Fibroínas , Humanos , Neuronas , Seda , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Skeletal muscle tissue engineering (SMTE) employs designed biomaterial scaffolds for promoting myogenic differentiation of myoblasts to functional myotubes. Oxidative stress plays a significant role in the biocompatibility of biomaterials as well as in the fate of myoblasts during myogenesis and is also associated with pathological conditions such as myotonic dystrophy. The inherent electrical excitability of muscle cells inspired the use of electroactive scaffolds for SMTE. Conducting polymers attracted the attention of researchers for their use in muscle tissue engineering. However, poor biocompatibility, biodegradability and development of oxidative stress associated immunogenic response limits the extensive use of synthetic conducting polymers for SMTE. In order to address the limitations of synthetic polymers, intrinsically electroactive and antioxidant silk fibroin/melanin composite films and electrospun fiber mats were fabricated and evaluated as scaffolds for promoting myogenesis in vitro. Melanin incorporation modulated the thermal stability, electrical conductivity of scaffolds, fiber alignment in electrospun mats and imparted good antioxidant properties to the scaffolds. The composite electrospun scaffolds promoted myoblast assembly and differentiation into uniformly aligned high aspect ratio myotubes. The results highlight the significance of scaffold topography along with conductivity in promoting myogenesis and the potential application of silk nanofibrous composite as electoractive platform for SMTE.
Asunto(s)
Fibroínas/química , Fibroínas/farmacología , Músculo Esquelético/efectos de los fármacos , Nanofibras/química , Pigmentos Biológicos/química , Seda/química , Seda/farmacología , Animales , Antioxidantes/química , Antioxidantes/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Bombyx/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Melaninas/química , Ratones , Desarrollo de Músculos/efectos de los fármacos , Fibras Musculares Esqueléticas/efectos de los fármacos , Mioblastos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Polímeros/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Understanding the roles of various parameters in orchestrating the preferential chiral molecular organization in supramolecular self-assembly processes is of great significance in designing novel molecular functional systems. Cyclic dipeptide (CDP) chiral auxiliary-functionalized naphthalenediimides (NCDPs 1-6) have been prepared and their chiral self-assembly properties have been investigated. Detailed photophysical and circular dichroism (CD) studies have unveiled the crucial role of the solvent in the chiral aggregation of these NCDPs. NCDPs 1-3 form supramolecular helical assemblies and exhibit remarkable chiroptical switching behaviour (M- to P-type) depending on the solvent composition of HFIP and DMSO. The strong influence of solvent composition on the supramolecular chirality of NCDPs has been further corroborated by concentration and solid-state thin-film CD studies. The chiroptical switching between supramolecular aggregates of opposite helicity (M and P) has been found to be reversible, and can be achieved through cycles of solvent removal and redissolution in solvent mixtures of specific composition. The control molecular systems (NCDPs 4-6), with an achiral or D-isomer second amino acid in the CDP auxiliary, did not show chiral aggregation properties. The substantial roles of hydrogen bonding and π-π interactions in the assembly of the NCDPs have been validated through nuclear magnetic resonance (NMR), photophysical, and computational studies. Quantum chemical calculations at the ab initio, semiempirical, and density functional theory levels have been performed on model systems to understand the stabilities of the right (P-) and left (M-) handed helical supramolecular assemblies and the nature of the intermolecular interactions. This study emphasizes the role of CDP chiral auxiliaries on the solvent-induced helical assembly and reversible chiroptical switching of naphthalenediimides.