Higher Ratios of Hyaluronic Acid Enhance Chondrogenic Differentiation of Human MSCs in a Hyaluronic Acid–Gelatin Composite Scaffold

Pfeifer, Christian; Berner, Arne; Koch, Matthias; Krutsch, Werner; Kujat, Richard; Angele, Peter; Nerlich, Michael; Zellner, Johannes

doi:10.3390/ma9050381

Cited by 34 publications

(30 citation statements)

References 39 publications

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“…In fact, a recent study also showed that supplementation with HA leads to a lower expression of collagen type II (Amann, Wolff, Breel, van Griensven, & Balmayor, ). These results disagreed with another recent study, which indicated that higher HA resulted in a higher expression of chondrogenic gene marker genes at Days 1, 4, and 7 (Pfeifer et al, ). However, it should be noted that such an enhancement was not observed after a longer culture (21 days).…”

Section: Resultscontrasting

confidence: 99%

“…In (b), no statistical difference was found (n = 4) [Colour figure can be viewed at wileyonlinelibrary.com] FIGURE 3 Expression of chondrogenic (SOX 9, AGG, and COL2) and hypertrophic (COL10) marker genes in cells within different constructs was examined after 8 weeks (n = 4) with HA leads to a lower expression of collagen type II (Amann, Wolff, Breel, van Griensven, & Balmayor, 2017). These results disagreed with another recent study, which indicated that higher HA resulted in a higher expression of chondrogenic gene marker genes at Days 1, 4, and 7 (Pfeifer et al, 2016). However, it should be noted that such an enhancement was not observed after a longer culture (21 days).…”

Section: Figurementioning

confidence: 79%

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Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect

Lin

Beck

Shimomura

et al. 2019

J Tissue Eng Regen Med

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Summary There is no therapy currently available for fully repair of articular cartilage lesion. Our laboratory has recently developed a visible light-activatable methacrylated gelatin (mGL) hydrogel with the potential for cartilage regeneration. In this study, we further optimized mGL scaffolds by supplementing methacrylated hyaluronic acid (mHA), which has been shown to stimulate chondrogenesis via activation of critical cellular signaling pathways. We hypothesized that the introduction of an optimal ratio of mHA would enhance the biological properties of mGL scaffolds and augment chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). To test this hypothesis, hybrid scaffolds consisting of mGL and mHA at different weight ratios were fabricated with hBMSCs encapsulated at 20×106 cells/mL and maintained in a chondrogenesis-promoting medium. The chondrogenenic differentiation of hBMSCs within different scaffolds was estimated after 8 weeks of culture. Our results showed that mGL/mHA at a 9:1 (%, w/v) ratio resulted in the lowest hBMSC hypertrophy and highest glycosaminoglycan production, with slightly increased volume of the entire construct. The applicability of this optimally designed mGL/mHA hybrid scaffold for cartilage repair was then examined in vivo. A full-thickness cylindrical osteochondral defect was surgically created in the rabbit femoral condyle and a 3-dimensional cell-biomaterial construct was fabricated by in situ photo-crosslinking to fully fill the lesion site. The results showed that implantation of the mGL/mHA (9:1) construct resulted in both cartilage and subchondral bone regeneration after 12 weeks, supporting its use as a promising scaffold for repair and resurfacing of articular cartilage defects in the clinical setting.

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Section: Resultscontrasting

confidence: 99%

Section: Figurementioning

confidence: 79%

Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect

Lin

Beck

Shimomura

et al. 2019

J Tissue Eng Regen Med

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“…Combining the advantages offered by gelatin and HA towards chondrocytes, gelatin/HA scaffolds (including cryogel scaffolds) have been shown to be suitable for applications in cartilage tissue engineering [16,17,18,19]. Nonetheless, from a tissue engineering point of view, the incorporation of a bioactive signal molecule into gelatin/HA scaffolds to promote chondrogenesis seems to be a rational approach to further enhance their functions.…”

Section: Introductionmentioning

confidence: 99%

Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering

Chen

Kuo

Wang

et al. 2016

IJMS

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Glucosamine (GlcN) fulfills many of the requirements as an ideal component in scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a gelatin/hyaluronic acid (GH) cryogel scaffold could provide biological cues in maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with GlcN may also decrease the crosslinking density and modulate the mechanical properties of the cryogel scaffold, which may be beneficial as physical cues for chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9% GlcN (GH-GlcN9) and 16% GlcN (GH-GlcN16) by carbodiimide-mediated crosslinking reactions at −16 °C. The crosslinking density and the mechanical properties of the cryogel matrix could be tuned by adjusting the content of GlcN used during cryogel preparation. In general, incorporation of GlcN did not influence scaffold pore size and ultimate compressive strain but increased porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation rate in hyaluronidase and collagenase solutions. On the contrary, the Young’s modulus, storage modulus, ultimate compressive stress, energy dissipation level, and rate of stress relaxation decreased by increasing the GlcN content in the cryogel. The release of GlcN from the scaffolds in the culture medium of chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7 days for GH-GlcN9. In vitro cell culture experiments using rabbit articular chondrocytes revealed that GlcN incorporation affected cell proliferation, morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed the best performance in maintaining chondrogenic phenotype with reduced cell proliferation rate but enhanced glycosaminoglycans (GAGs) and type II collagen (COL II) secretion. Quantitative real-time polymerase chain reaction also showed time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan and Sox9) for GH-GlcN16. Implantation of chondrocytes/GH-GlcN16 constructs into full-thickness articular cartilage defects of rabbits could regenerate neocartilage with positive staining for GAGs and COL II. The GH-GlcN16 cryogel will be suitable as a scaffold for the treatment of articular cartilage defects.

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“…Jiang et al demonstrated superior chondrogenic differentiation of MSC embedded in Col compared to MSC only in a rat model [50]. On the other hand, HA has been combined with Col 1 or gelatin before with similar outcomes that chondrogenic differentiation is promoted in the composite compared to HA or Col only [51][52][53]. One limitation of the present technique is the shear-induce alignment, limiting the degrees of spatial freedom in fibril arrangement.…”

Section: Discussionmentioning

confidence: 92%

Tissue mimetic hyaluronan bioink containing collagen fibers with controlled orientation modulating cell morphology and alignment

Schwab

Hélary

Richards

et al. 2020

Preprint

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Biofabrication is providing scientists and clinicians the ability to produce engineered tissues with desired shapes, chemical and biological gradients. Typical resolutions achieved with extrusion-based bioprinting are at the macroscopic level. However, for capturing the fibrillar nature of the extracellular matrix (ECM), it is necessary to arrange ECM components at smaller scales, down to the sub-micron and the molecular level. In this study, we introduce a (bio)ink containing hyaluronan (HA) as tyramine derivative (THA) and collagen (Col). Similarly to other connective tissues, in this (bio)ink Col is present in fibrillar form and HA as viscoelastic space filler. THA was enzymatically crosslinked under mild conditions allowing simultaneous Col fibrillogenesis, thus achieving a homogeneous distribution of Col fibrils within the viscoelastic HA-based matrix. THA-Col composite displayed synergistic properties in terms of storage modulus and shear-thinning, translating into good printability. Shear-induced alignment of the Col fibrils along the printing direction was achieved and quantified via immunofluorescence and second harmonic generation. Cell-free and cell-laden constructs were printed and characterized, analyzing the influence of the controlled microscopic anisotropy on cell behavior and chondrogenic differentiation. THA-Col showed cell instructive properties modulating hMSC adhesion, morphology and sprouting from spheroids stimulated by the presence and the orientation of Col fibers. Actin filament staining showed that hMSCs embedded into aligned constructs displayed increased cytoskeleton alignment along the fibril direction. Based on gene expression of cartilage/bone markers and matrix production, hMSCs embedded into the bioink displayed chondrogenic differentiation comparable or superior to standard pellet culture by means of proteoglycan production (Safranin O staining and proteoglycan quantification) as well as increase in cartilage related genes. The possibility of printing matrix components with control over microscopic alignment brings biofabrication one step closer to capturing the complexity of native tissues.

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Higher Ratios of Hyaluronic Acid Enhance Chondrogenic Differentiation of Human MSCs in a Hyaluronic Acid–Gelatin Composite Scaffold

Cited by 34 publications

References 39 publications

Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect

Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect

Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering

Tissue mimetic hyaluronan bioink containing collagen fibers with controlled orientation modulating cell morphology and alignment

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