Density Gradient Multilayered Polymerization (DGMP): A Novel Technique for Creating Multi-compartment, Customizable Scaffolds for Tissue Engineering
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Complex tissue culture matrices, in which types and concentrations of biological stimuli (e.g. growth factors, inhibitors, or small molecules) or matrix structure (e.g. composition, concentration, or stiffness of the matrix) vary over space, would enable a wide range of investigations concerning how these variables affect cell differentiation, migration, and other phenomena. The major challenge in creating layered matrices is maintaining the structural integrity of layer interfaces without diffusion of individual components from each layer1. Current methodologies to achieve this include photopatterning2-3, lithography4, sequential functionalization5, freeze drying6, microfluidics7, or centrifugation8, many of which require sophisticated instrumentation and technical skills. Others rely on sequential attachment of individual layers, which may lead to delamination of layers9. DGMP overcomes these issues by using an inert density modifier such as iodixanol to create layers of varying densities10. Since the density modifier can be mixed with any prepolymer or bioactive molecule, DGMP allows each scaffold layer to be customized. Simply varying the concentration of the density modifier prevents mixing of adjacent layers while they remain aqueous. Subsequent single step polymerization gives rise to a structurally continuous multilayered scaffold, in which each layer has distinct chemical and mechanical properties. The density modifier can be easily removed with sufficient rinsing without perturbation of the individual layers or their components. This technique is therefore well suited for creating hydrogels of various sizes, shapes, and materials. A protocol for fabricating a 2D-polyethylene glycol (PEG) gel, in which alternating layers incorporate RGDS-350, is outlined below. We use PEG because it is biocompatible and inert. RGDS, a cell adhesion peptide11, is used to demonstrate spatial restriction of a biological cue, and the conjugation of a fluorophore (Alexa Fluor 350) enables us to visually distinguish various layers. This procedure can be adapted for other materials (e.g. collagen, hyaluronan, etc.) and can be extended to fabricate 3D gels with some modifications10.Keywords:
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This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding.
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Tissue damage and disease impose a significant burden on individuals, society, and the economy. Current tissue engineering techniques have limitations, and improvements are necessary to more effectively repair or regenerate damaged or diseased tissues. Hydrogels, a type of synthetic scaffold, have gained increasing attention in tissue engineering due to their mechanical support for cells, customizable characteristics, and potential to overcome challenges in specific applications. However, the full extent of their effectiveness and capabilities in tissue engineering is not yet determined. This research paper aims to analyze the uses and capabilities of hydrogels in tissue engineering through a meta-analysis of various studies, contributing to the advancement of regenerative medicine. Hydrogels present a versatile and promising scaffold for tissue engineering, with the potential to significantly improve the field of regenerative medicine.
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Treballs Finals de Grau de Fisica, Facultat de Fisica, Universitat de Barcelona, Curs: 2017, Tutores : Elena Martinez, Gizem Altay
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Hybrid fiber composites are novel materials used for different promising applications in the field of biomedicine because of their well-known potential properties such as thermal, mechanical, and gelling properties. Nowadays, these materials are receiving great attention in all fields. These potential hybrid fiber composite scaffold hydrogels are well known because of their wide applications in biomedicine. These hydrogels are extracted and made into scaffolds in different ways and techniques. To design a novel type of scaffold, these hydrogel scaffolds play a key role in approaching potential applications. Because of their shape, size, and flexibility, these hydrogel-based scaffolds are considered as useful materials in tissue engineering and other biomedical applications. These hydrogels provide new techniques and approaches in tissue engineering. In this chapter, we describe novel hydrogel-based scaffolds as fiber composites for different biomedical applications, especially in tissue engineering, skin regeneration, and cardiac vascular tissue engineering; explain how to formulate these scaffold hydrogel fiber composites; and discuss the challenges of these hydrogels in modern life.
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Designing of biologically active scaffolds with optimal characteristics is one of the key factors for successful tissue engineering. Recently, hydrogels have received a considerable interest as leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix, in addition to their desirable framework for cellular proliferation and survival. More recently, the ability to control the shape, porosity, surface morphology, and size of hydrogel scaffolds has created new opportunities to overcome various challenges in tissue engineering such as vascularization, tissue architecture and simultaneous seeding of multiple cells. This review provides an overview of the different types of hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and the recent applications of hydrogels in tissue engineering. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, the challenges associated with the use of hydrogel scaffolds were described.
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Among the diversity of scaffolding systems available, hydrogel remains a popular choice for tissue engineering applications. The current state-of-the-art bioresponsive hydrogels demand intricate designs in pursuit of acquiring desired timely responses, such as controlled release of biological factors, changes in mechanical properties and scaffold degradation, at the same rate as the natural extracellular matrix. In this review, a variety of bioresponsive hydrogels are discussed; in particular, bioactive and biodegradable hydrogels that facilitate cellular development and tissue morphogenesis are highlighted. Bioactive hydrogels are designed to deliver biomolecules such as cell-adhesive moieties and instructive ligands at close proximity to the cell for better uptake or exposure. Biodegradable hydrogels provide transient scaffolding support for therapeutic cell settlement while gradually degrading in response to physical or enzymatic stimuli. In addition, biomechanical stimuli from hydrogels can induce mutual constructive responses on cells and, hence, will also be covered in this review.
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