Alginate Hydrogel Has a Negative Impact on in Vitro Collagen 1 Deposition by Fibroblasts

Smith, Alan M.; Hunt, Nicola; Shelton, Richard M.; Birdi, Gurpreet; Grover, Liam M.

doi:10.1021/bm301321d

Cited by 22 publications

(13 citation statements)

References 36 publications

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“…For poly(ethylene glycol) hydrogels, it has been shown that increasing polymer densities efficiently limit the transport of ECM molecules through the gel, resulting in strong pericellular localizations, even of the relatively small glycosaminoglycans [5]. Another study, using alginate hydrogels as immobilization matrix [28], argued differently on the issue of ECM molecule transport. They found procollagens escaping the hydrogels to the culture medium, and argued that both procollagen and BMP-1, being negatively charged, can diffuse through the gel, which is also negatively charged.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Structural Characterization of Neocartilage Formed by Mesenchymal Stem Cells in Alginate Hydrogels

et al. 2014

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A popular approach to make neocartilage in vitro is to immobilize cells with chondrogenic potential in hydrogels. However, functional cartilage cannot be obtained by control of cells only, as function of cartilage is largely dictated by architecture of extracellular matrix (ECM). Therefore, characterization of the cells, coupled with structural and biochemical characterization of ECM, is essential in understanding neocartilage assembly to create functional implants in vitro. We focused on mesenchymal stem cells (MSC) immobilized in alginate hydrogels, and used immunohistochemistry (IHC) and gene expression analysis combined with advanced microscopy techniques to describe properties of cells and distribution and organization of the forming ECM. In particular, we used second harmonic generation (SHG) microscopy and focused ion beam/scanning electron microscopy (FIB/SEM) to study distribution and assembly of collagen. Samples with low cell seeding density (1e7 MSC/ml) showed type II collagen molecules distributed evenly through the hydrogel. However, SHG microscopy clearly indicated only pericellular localization of assembled fibrils. Their distribution was improved in hydrogels seeded with 5e7 MSC/ml. In those samples, FIB/SEM with nm resolution was used to visualize distribution of collagen fibrils in a three dimensional network extending from the pericellular region into the ECM. In addition, distribution of enzymes involved in procollagen processing were investigated in the alginate hydrogel by IHC. It was discovered that, at high cell seeding density, procollagen processing and fibril assembly was also occurring far away from the cell surface, indicating sufficient transport of procollagen and enzymes in the intercellular space. At lower cell seeding density, the concentration of enzymes involved in procollagen processing was presumably too low. FIB/SEM and SHG microscopy combined with IHC localization of specific proteins were shown to provide meaningful insight into ECM assembly of neocartilage, which will lead to better understanding of cartilage formation and development of new tissue engineering strategies.

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Section: Discussionmentioning

confidence: 99%

Biochemical and Structural Characterization of Neocartilage Formed by Mesenchymal Stem Cells in Alginate Hydrogels

et al. 2014

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“…Initially, this was thought to be principally a consequence of the modulus of the materials, but more recently reports have suggested that this can be modified by changing the distribution of grafted adhesion moieties and the nature of the interactions that may be formed with the polymer chain . It has become clear that the level of entrapment that can be provided by the relatively stiff quiescently gelled matrix can have a significant influence on biological properties, including the capacity of cells to proliferate, maintain specific phenotypes or even secrete functional protein molecules as shown in Figure …”

Section: The Delivery Of Biological Therapeutics Using Hydrogelsmentioning

confidence: 99%

Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications

et al. 2018

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The development of new materials for clinical use is limited by an onerous regulatory framework, which means that taking a completely new material into the clinic can make translation economically unfeasible. One way to get around this issue is to structure materials that are already approved by the regulator, such that they exhibit very distinct physical properties and can be used in a broader range of clinical applications. Here, the focus is on the structuring of soft materials at multiple length scales by modifying processing conditions. By applying shear to newly forming materials, it is possible to trigger molecular reorganization of polymer chains, such that they aggregate to form particles and ribbon-like structures. These structures then weakly interact at zero shear forming a solid-like material. The resulting self-healing network is of particular use for a range of different biomedical applications. How these materials are used to allow the delivery of therapeutic entities (cells and proteins) and as a support for additive layer manufacturing of larger-scale tissue constructs is discussed. This technology enables the development of a range of novel materials and structures for tissue augmentation and regeneration.

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“…It has been incorporated into collagen-based scaffolds to improve their structural stability[47]. However, alginate by itself negatively impacts collagen type one deposition from dermal fibroblasts, potentially making them a non-ideal polymer for skin substitutes[80]. Alginate has been largely considered an ideal polymer for skin printers, devices that seed skin cells onto prefabricated biodegradable scaffolds, due to its ionic cross-linking mechanism[81,82].…”

Section: Components Of a Skin Substitutementioning

confidence: 99%

Methodologies in creating skin substitutes

Nicholas

Jeschke

Amini-Nik

2016

Cell. Mol. Life Sci.

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The creation of skin substitutes has significantly decreased morbidity and mortality of skin wounds. Although there are still a number of disadvantages of currently available skin substitutes, there has been a significant decline in research advances over the past several years in improving these skin substitutes. Clinically most skin substitutes used are acellular and do not use growth factors to assist wound healing, key areas of potential in this field of research. This article discusses the five necessary attributes of an ideal skin substitute. It comprehensively discusses the three major basic components of currently available skin substitutes: scaffold materials, growth factors, and cells, comparing and contrasting what has been used so far. It then examines a variety of techniques in how to incorporate these basic components together to act as a guide for further research in the field to create cellular skin substitutes with clinically better results.

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Alginate Hydrogel Has a Negative Impact on in Vitro Collagen 1 Deposition by Fibroblasts

Cited by 22 publications

References 36 publications

Biochemical and Structural Characterization of Neocartilage Formed by Mesenchymal Stem Cells in Alginate Hydrogels

Biochemical and Structural Characterization of Neocartilage Formed by Mesenchymal Stem Cells in Alginate Hydrogels

Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications

Methodologies in creating skin substitutes

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