Modifications of Hyaluronan Influence the Interaction with Human Bone Morphogenetic Protein-4 (hBMP-4)

Hintze, Vera; Moeller, Stephanie; Schnabelrauch, Matthias; Bierbaum, Susanne; Viola, Manuela; Worch, H.; Scharnweber, Dieter

doi:10.1021/bm9008827

Cited by 130 publications

(154 citation statements)

References 45 publications

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“…Recently, we could show that SO 3 / pyridine is a mild sulfating agent for GAGs such as hyaluronan allowing proper control of the degree of sulfation, especially if a homogeneous sulfate group distribution and rather low DS S values are desired. 46,47 We therefore decided to use SO 3 /pyridine for the sulfation of alginate. In our work, addition of 3 mM CaCl 2 was necessary to maintain stability of the gel for the first 21 days of culture.…”

Section: Discussionmentioning

confidence: 99%

Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

Mhanna

Kashyap

Palazzolo

et al. 2014

Tissue Engineering Part A

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100

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The loss of expression of chondrogenic markers during monolayer expansion remains a stumbling block for cell-based treatment of cartilage lesions. Here, we introduce sulfated alginate hydrogels as a cartilage biomimetic biomaterial that induces cell proliferation while maintaining the chondrogenic phenotype of encapsulated chondrocytes. Hydroxyl groups of alginate were converted to sulfates by incubation with sulfur trioxidepyridine complex (SO 3 /pyridine), yielding a sulfated material cross-linkable with calcium chloride. Passage 3 bovine chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up to 35 days. Cell proliferation was five-fold higher in alginate sulfate compared with alginate ( p = 0.038). Blocking beta1 integrins in chondrocytes within alginate sulfate hydrogels significantly inhibited proliferation ( p = 0.002). Sulfated alginate increased the RhoA activity of chondrocytes compared with unmodified alginate, an increase that was blocked by b1 blocking antibodies ( p = 0.017). Expression and synthesis of type II collagen, type I collagen, and proteoglycan was not significantly affected by the encapsulation material evidenced by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Alginate sulfate constructs showed an opaque appearance in culture, whereas the unmodified alginate samples remained translucent. In conclusion, alginate sulfate provides a three dimensional microenvironment that promotes both chondrocyte proliferation and maintenance of the chondrogenic phenotype and represents an important advance for chondrocyte-based cartilage repair therapies providing a material in which cell expansion can be done in situ.

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Section: Discussionmentioning

confidence: 99%

Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

Mhanna

Kashyap

Palazzolo

et al. 2014

Tissue Engineering Part A

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100

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“…The low-and high-sulfated HA derivatives (sHA1, sHA4) were synthesized and characterized as described previously 22,31 . Low molecular weight HA (LMW-HA) was prepared by ozonolysis of high molecular weight native HA.…”

Section: Preparation Of Modified Ha Derivativesmentioning

confidence: 99%

Bioinspired Collagen/Glycosaminoglycan-Based Cellular Microenvironments for Tuning Osteoclastogenesis

Rother

Salbach-Hirsch

Moeller

et al. 2015

ACS Appl. Mater. Interfaces

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Replicating the biocomplexity of native extracellular matrices (ECM) is critical for a deeper understanding of biochemical signals influencing bone homeostasis. This will foster the development of bioinspired biomaterials with adjustable bone-inducing properties. Collagen-based coatings containing single HA derivatives have previously been reported to promote osteogenic differentiation and modulate osteoclastogenesis and resorption depending on their sulfation degree. However, the potential impact of different GAG concentrations as well as the interplay of multiple GAGs in these coatings is not characterized in detail to date. These aspects were addressed in the current study by integrating HA and different sulfate-modified HA derivatives (sHA) during collagen in vitro fibrillogenesis. Besides cellular microenvironments with systematically altered single-GAG concentrations, matrices containing both low and high sHA (sHA1, sHA4) were characterized by biochemical analysis such as agarose gel electrophoresis, performed for the first time with sHA derivatives. The morphology and composition of the collagen coatings were altered in a GAG sulfation- and concentration-dependent manner. In multi-GAG microenvironments, atomic force microscopy revealed intermediate collagen fibril structures with thin fibrils and microfibrils. GAG sulfation altered the surface charge of the coatings as demonstrated by ζ-potential measurements revealed for the first time as well. This highlights the prospect of GAG-containing matrices to adjust defined surface charge properties. The sHA4- and the multi-GAG coatings alike significantly enhanced the viability of murine osteoclast-precursor-like RAW264.7 cells. Although in single-GAG matrices there was no dose-dependent effect on cell viability, osteoclastogenesis was significantly suppressed only on sHA4-coatings in a dose-dependent fashion. The multi-GAG coatings led to an antiosteoclastogenic effect in-between those with single-GAGs which cannot simply be attributed to the overall content of sulfate groups. These data suggest that the interplay of sGAGs influences bone cell behavior. Whether these findings translate into favorable biomaterial properties needs to be validated in vivo.

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“…Sulfated derivatives of HA (sHA3), CS (sCS3) and a thermally degraded low molecular weight HA of comparable length were synthesized and characterized as previously described [13,14]. The chart in Fig.…”

Section: Preparation Of Gag Derivativesmentioning

confidence: 99%

Structural and functional insights into sclerostin-glycosaminoglycan interactions in bone

Salbach-Hirsch¹,

Samsonov²,

Hintze³

et al. 2015

Biomaterials

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Modifications of Hyaluronan Influence the Interaction with Human Bone Morphogenetic Protein-4 (hBMP-4)

Cited by 130 publications

References 45 publications

Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

Bioinspired Collagen/Glycosaminoglycan-Based Cellular Microenvironments for Tuning Osteoclastogenesis

Structural and functional insights into sclerostin-glycosaminoglycan interactions in bone

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