Injectable Biodegradable Poly(ethylene glycol)/RGD Peptide Hybrid Hydrogels for in vitro Chondrogenesis of Human Mesenchymal Stem Cells

Liu, Shao Qiong; Tian, Quan; Wang, Lei; Hedrick, James L.; Hui, James; Yang, Yi Yan; Ee, Pui Lai Rachel

doi:10.1002/marc.200900818

Cited by 70 publications

(46 citation statements)

References 29 publications

(36 reference statements)

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“…Several studies have employed RGD sequences for improving cell adhesion, 24 viability 29 and chondrogenesis 16,31,32 of stem cells in 3D PEG gels. However, very few studies investigated the incorporation of the GFOGER peptide in 3D hydrogels and their influence on chondrogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 Modification of hydrogels with small functional groups such as amines and phosphates induced differentiation of stem cells into the osteogenic or adipogenic pathways. 28 Further, the introduction of adhesion sequences such as RGD into materials has shown its role in adhesion, 24 viability, 29 proliferation, 30 and differentiation of stem cells, 31,32 however, an inhibition of chondrogenesis was also reported in RGDmodified alginate hydrogels. 33 Chondrocytes form primary interactions with type II collagen and hyaluronic acid in the pericellular matrix.…”

Section: Introductionmentioning

confidence: 99%

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GFOGER-Modified MMP-Sensitive Polyethylene Glycol Hydrogels Induce Chondrogenic Differentiation of Human Mesenchymal Stem Cells

Mhanna

Öztürk

Vallmajó-Martín

et al. 2014

Tissue Engineering Part A

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The cellular microenvironment plays a crucial role in directing proliferation and differentiation of stem cells. Cells interact with their microenvironment via integrins that recognize certain peptide sequences of extracellular matrix proteins. This receptor-ligand binding has profound impact on cell fate. Interactions of human bone marrow mesenchymal stem cells (hMSCs) with the triple helical collagen mimetic, GPC(GPP)5-GFOGER-(GPP)5GPC-NH2, and the fibronectin adhesion peptide, RGD, were studied in degradable or nondegradable polyethylene glycol (PEG) gels formed by Michael-type addition chemistry. Proliferation, cytoskeletal morphology, and chondrogenic differentiation of encapsulated hMSCs were evaluated. The hMSCs adopted a highly spread morphology within the GFOGER-modified gels, whereas RGD induced a star-like spreading of the cells. hMSCs within GFOGER-modified degradable gels had a high proliferation rate compared with cells in peptide-free gels ( p = 0.017). Gene expression of type II collagen was highest in GFOGER-modified degradable gels after 21 days. Peptide incorporation increased GAG production in degradable gels after 7 and 21 days and GFOGER-modified degradable hydrogels had on average the highest GAG content, a finding that was confirmed by Alcian blue staining. In conclusion, the GFOGER peptide enhances proliferation in degradable PEG gels and provides a better chondrogenic microenvironment compared with the RGD peptide.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GFOGER-Modified MMP-Sensitive Polyethylene Glycol Hydrogels Induce Chondrogenic Differentiation of Human Mesenchymal Stem Cells

Mhanna

Öztürk

Vallmajó-Martín

et al. 2014

Tissue Engineering Part A

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“…Similarly, Pep1Alloc concentration may be adjusted for different applications (e.g., 0.2-5 mM) as reported in literature for thiol-functionalized peptides. [18][19][20][21] LAP concentration is recommended around 0.067 wt% (2.2 mM) or less, as described, as higher concentrations can decrease cell viability. 4.…”

Section: Introductionmentioning

confidence: 99%

Light-mediated Formation and Patterning of Hydrogels for Cell Culture Applications

Sawicki

Kloxin

2016

JoVE

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Click chemistries have been investigated for use in numerous biomaterials applications, including drug delivery, tissue engineering, and cell culture. In particular, light-mediated click reactions, such as photoinitiated thiol−ene and thiol−yne reactions, afford spatiotemporal control over material properties and allow the design of systems with a high degree of user-directed property control. Fabrication and modification of hydrogel-based biomaterials using the precision afforded by light and the versatility offered by these thiol−X photoclick chemistries are of growing interest, particularly for the culture of cells within well-defined, biomimetic microenvironments. Here, we describe methods for the photoencapsulation of cells and subsequent photopatterning of biochemical cues within hydrogel matrices using versatile and modular building blocks polymerized by a thiol−ene photoclick reaction. Specifically, an approach is presented for constructing hydrogels from allyloxycarbonyl (Alloc)-functionalized peptide crosslinks and pendant peptide moieties and thiol-functionalized poly(ethylene glycol) (PEG) that rapidly polymerize in the presence of lithium acylphosphinate photoinitiator and cytocompatible doses of long wavelength ultraviolet (UV) light. Facile techniques to visualize photopatterning and quantify the concentration of peptides added are described. Additionally, methods are established for encapsulating cells, specifically human mesenchymal stem cells, and determining their viability and activity. While the formation and initial patterning of thiol-alloc hydrogels are shown here, these techniques broadly may be applied to a number of other light and radical-initiated material systems (e.g., thiol-norbornene, thiol-acrylate) to generate patterned substrates.

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“…One approach is to incorporate pro-chondrogenic factors into biomaterials. Biomaterial scaffolds impregnated with BMP, TGF-β, or IGF maintain the differentiated phenotype of adult chondrocytes and promote chondrogenesis by MSC in vitro [166][167][168][169], and successful in vivo repair of articular cartilage defects in animal models has been reported in some studies using MSC seeded into TGF-β-containing biomaterial scaffolds [169,170]. However, other studies using a similar approach did not result in improved in vivo cartilage repair [171,172], and in one case led to a foreign body reaction [171].…”

Section: Growth Factorsmentioning

confidence: 99%

The Potential of Human Embryonic Stem Cells for Articular Cartilage Repair and Osteoarthritis Treatment

Fisher

Ferrari²,

Li³

et al. 2012

Rheumatol Curr Res

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Osteoarthritis is a debilitating joint disease present in epidemic proportions worldwide. Osteoarthritis results from degeneration of the articular cartilage of the joint surfaces due to acute trauma, or chronic wear and tear. Due to limited ability of cartilage to repair itself, and lack of available treatments, there is an urgent need for development of approaches to repair articular cartilage damage due to injury or osteoarthritic disease. Cell-based repair strategies are among the most promising of these approaches. Various adult cell sources for cartilage repair are proposed including autologous adult chondrocytes as well as adult Mesenchymal Stem Cells (MSC). Disadvantages such as destructive harvest protocols; poor proliferation, and particularly for MSC, considerable cellular heterogeneity, have limited success of these cell types for cartilage repair. Chondrogenic cells derived from human embryonic stem cells (hESC) offer a highly proliferative cell source, which when directed into the chondrogenic lineage, could provide an ideal source of cells for cartilage repair. Chondrogenic cells derived from human induced pluripotent stem cells (iPSC) offer additional advantages for patient-specific therapy. Recently protocols have been established for directed differentiation of hESC into the chondrogenic lineage. Harnessing the potential of hESC-derived chondrogenic cells will require comprehensive testing of their efficacy for in vivo cartilage repair, as well as considerations of safety and immunogenicity of the cells. Use of pro-chondrogenic factors and/or bioactive scaffolds may assist in optimizing cartilage repair by chondrogenic cells. Repair of cartilage damage in osteoarthritis is a special challenge because of the widespread damage and presence of signals and stressors which disrupt normal joint homeostasis. Particular promise in cell-based repair of osteoarthritis may be provided by chondrogenic progenitor cells which may mimic endogenous repair responses. This review discusses the current status of cell-based cartilage repair strategies and in particular the potential role of hESC-derived chondrocytes or chondroprogenitor cells for treatment of articular cartilage damage due to injury and osteoarthritis.

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Injectable Biodegradable Poly(ethylene glycol)/RGD Peptide Hybrid Hydrogels for in vitro Chondrogenesis of Human Mesenchymal Stem Cells

Cited by 70 publications

References 29 publications

GFOGER-Modified MMP-Sensitive Polyethylene Glycol Hydrogels Induce Chondrogenic Differentiation of Human Mesenchymal Stem Cells

GFOGER-Modified MMP-Sensitive Polyethylene Glycol Hydrogels Induce Chondrogenic Differentiation of Human Mesenchymal Stem Cells

Light-mediated Formation and Patterning of Hydrogels for Cell Culture Applications

The Potential of Human Embryonic Stem Cells for Articular Cartilage Repair and Osteoarthritis Treatment

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