Gelatin—Hyaluronic Acid Hydrogels with Tuned Stiffness to Counterbalance Cellular Forces and Promote Cell Differentiation

Poveda-Reyes, Sara; Moulisová, Vladimíra; Sanmartín-Masiá, Esther; Quintanilla‐Sierra, Luis; Salmerón‐Sánchez, Manuel; Ferrer, Gloria Gallego

doi:10.1002/mabi.201500469

Cited by 55 publications

(57 citation statements)

References 73 publications

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“…High viability and the ability to print with varying cell number have been demonstrated shortly after printing as well as after 14 days of maintenance in vitro . Cell‐laden constructs tended to slightly shrink during culture, which has been shown by other authors as a result of tissue remodeling through matrix–cell interaction or matrix degradation and synthesis . Gelatin and HA are prone to such cell‐driven modifications through their natural origin, being advantageous for cell differentiation processes such as chondrocyte redifferentiation observed in this study.…”

Section: Discussionsupporting

confidence: 79%

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Lam¹,

et al. 2019

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To create artificial cartilage in vitro, mimicking the function of native extracellular matrix (ECM) and morphological cartilage‐like shape is essential. The interplay of cell patterning and matrix concentration has high impact on the phenotype and viability of the printed cells. To advance the capabilities of cartilage bioprinting, we investigated different ECMs to create an in vitro chondrocyte niche. Therefore, we used methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (HAMA) in a stereolithographic bioprinting approach. Both materials have been shown to support cartilage ECM formation and recovery of chondrocyte phenotype. We used these materials as bioinks to create cartilage models with varying chondrocyte densities. The models maintained shape, viability, and homogenous cell distribution over 14 days in culture. Chondrogenic differentiation was demonstrated by cartilage‐typical proteoglycan and type II collagen deposition and gene expression (COL2A1, ACAN) after 14 days of culture. The differentiation pattern was influenced by cell density. A high cell density print (25 × 106 cells/mL) led to enhanced cartilage‐typical zonal segmentation compared to cultures with lower cell density (5 × 106 cells/mL). Compared to HAMA, GelMA resulted in a higher expression of COL1A1, typical for a more premature chondrocyte phenotype. Both bioinks are feasible for printing in vitro cartilage with varying differentiation patterns and ECM organization depending on starting cell density and chosen bioink. The presented technique could find application in the creation of cartilage models and in the treatment of articular cartilage defects using autologous material and adjusting the bioprinted constructs size and shape to the patient. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2649–2657, 2019.

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Section: Discussionsupporting

confidence: 79%

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Lam¹,

et al. 2019

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“…Entrapment of myoblast in a combination of HA and gelatin casted into a cylindrical hydrogel induced myotube differentiation. In this study, it was demonstrated that 58% of cells differentiated into myotubes with 30/70 gelatin/HA combination with the gel stiffness of 5.5 kPa . In terms of in vivo response HA hydrogel both methacrylated and thiolated have shown to reduce inflammatory responses in tissues such as the heart and spinal cord .…”

Section: Moving From 3d Cell‐entrapment Devices To Cell‐modulation Plmentioning

confidence: 79%

Toward Customized Extracellular Niche Engineering: Progress in Cell‐Entrapment Technologies

2017

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The primary aim in tissue engineering is to repair, replace, and regenerate dysfunctional tissues to restore homeostasis. Cell delivery for repair and regeneration is gaining impetus with our understanding of constructing tissue‐like environments. However, the perpetual challenge is to identify innovative materials or re‐engineer natural materials to model cell‐specific tissue‐like 3D modules, which can seamlessly integrate and restore functions of the target organ. To devise an optimal functional microenvironment, it is essential to define how simple is complex enough to trigger tissue regeneration or restore cellular function. Here, the purposeful transition of cell immobilization from a cytoprotection point of view to that of a cell‐instructive approach is examined, with advances in the understanding of cell–material interactions in a 3D context, and with a view to further application of the knowledge for the development of newer and complex hierarchical tissue assemblies for better examination of cell behavior and offering customized cell‐based therapies for tissue engineering.

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“…However, the maximum concentrations in the previous work were 1 mg mL −1 , because the studies were focused on adding CS to culture solutions as promoter of in vitro cell growth and differentiation . Here we tested concentrations of oxCS up to 5 mg mL −1 , which are required for formation of surface coatings, free‐standing multilayer films, and 3D systems like hydrogels . Indeed, we also expected a certain toxicity of the aldehyde groups of oxCS because they can react with amino groups in molecules and structures that are important for function of cells .…”

Section: Resultsmentioning

confidence: 99%

Effect of Sulfation Route and Subsequent Oxidation on Derivatization Degree and Biocompatibility of Cellulose Sulfates

Strätz

Liedmann

Heinze

et al. 2019

Macromolecular Bioscience

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as wound dressings. [2][3][4] Cellulose sulfates (CS) are well soluble in water and are more susceptible for enzymatic degradation compared to native cellulose. [5] CS have been used in biotechnology, for example, for encapsulation of enzymes and cells. [5] Moreover, it was observed in recent studies that CS possess a similar bioactivity like heparin with regard to inhibition of coagulation, but also when interacting with cytokines that regulate growth and differentiation of cells . [6][7][8] More specifically, it was observed that particularly regioselective sulfation was effective in increasing the binding of CS to the growth factors (GF) FGF-2 and BMP-2 that are related to mitogenic or angiogenic and osteogenic activities, respectively. [8][9][10] In these studies, it was also shown that CS possess a protecting effect on GF stabilizing them against proteolytic digestion by enzymes, which is one explanation for the bioactivity of CS. [11] Since CS represent polyelectrolytes, they have been used for the formation of bioactive surface coatings that guide adhesion and growth of cells using the layerby-layer technique complexing them with chitosan. [12] These observations show that CS possess a wide range of bioactivity that makes them interesting materials for several medical applications in making blood compatible coatings of hemodialysis membranes, coatings of solid implants or tissue engineering scaffolds, but also as components for formation of hydrogels or bioprinting. Sulfated cellulose (CS) represents an interesting biopolymer due to bioactivity comparable to heparin. However, use of CS for making surface coatings or hydrogels requires the presence of reactive groups for covalent reactions.Here, an approach is presented to oxidize cellulose sulfates for subsequent cross-linking reactions with amino groups to form imine bonds. Cellulose is sulfated by direct sulfation or acetosulfation, followed by a Malaprade oxidation. The CS obtained is characterized by elemental analysis and 13 C-NMR spectroscopy. The resulting oxidized cellulose sulfates (oxCS) have different degrees of sulfation ranging from 0.79 to 1.13 and oxidation degrees from 0.18 to 0.34, but also different mass average molecular mass (M W ). Toxicity studies are carried out with mouse 3T3 fibroblasts exposed to aqueous solutions of oxCS. The results show that all oxCS are non-toxic at lower concentrations (0.5 mg mL −1 ), but with both increasing degree of oxidation and concentrations, toxic effects are observed particularly for acetosulfated and lesser for direct sulfated oxCS, which is related to a decrease in the M W of the products. It is concluded that oxCS obtained by direct sulfation with M W above 70 kDa may represent a biocompatible material for the applications suggested above.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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Gelatin—Hyaluronic Acid Hydrogels with Tuned Stiffness to Counterbalance Cellular Forces and Promote Cell Differentiation

Cited by 55 publications

References 73 publications

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage

Toward Customized Extracellular Niche Engineering: Progress in Cell‐Entrapment Technologies

Effect of Sulfation Route and Subsequent Oxidation on Derivatization Degree and Biocompatibility of Cellulose Sulfates

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