Covalent Growth Factor Immobilization Strategies for Tissue Repair and Regeneration

Masters, Kristyn S.

doi:10.1002/mabi.201000505

Cited by 161 publications

(188 citation statements)

References 105 publications

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“…The bioactivity of growth factors presented in an immobilized form has also been shown in other studies, indicating that the release of the proteins and their subsequent internalization are not essential for cell stimulation 24,25 . In fact, the covalent immobilization of growth factors allows the sustained stimulation of the target cells while maintaining an effective dosage because of enhanced occupancy rate of different types of receptors at the cell membrane 22,23,[26][27][28] .…”

Section: Discussionmentioning

confidence: 99%

Covalent Binding of BMP-2 on Surfaces Using a Self-assembled Monolayer Approach

Pohl

Schwab

Cavalcanti‐Adam

2013

JoVE

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Bone morphogenetic protein 2 (BMP-2) is a growth factor embedded in the extracellular matrix of bone tissue. BMP-2 acts as trigger of mesenchymal cell differentiation into osteoblasts, thus stimulating healing and de novo bone formation. The clinical use of recombinant human BMP-2 (rhBMP-2) in conjunction with scaffolds has raised recent controversies, based on the mode of presentation and the amount to be delivered. The protocol presented here provides a simple and efficient way to deliver BMP-2 for in vitro studies on cells. We describe how to form a self-assembled monolayer consisting of a heterobifunctional linker, and show the subsequent binding step to obtain covalent immobilization of rhBMP-2. With this approach it is possible to achieve a sustained presentation of BMP-2 while maintaining the biological activity of the protein. In fact, the surface immobilization of BMP-2 allows targeted investigations by preventing unspecific adsorption, while reducing the amount of growth factor and, most notably, hindering uncontrolled release from the surface. Both short-and long-term signaling events triggered by BMP-2 are taking place when cells are exposed to surfaces presenting covalently immobilized rhBMP-2, making this approach suitable for in vitro studies on cell responses to BMP-2 stimulation. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

Covalent Binding of BMP-2 on Surfaces Using a Self-assembled Monolayer Approach

Pohl

Schwab

Cavalcanti‐Adam

2013

JoVE

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“…Therefore, controlled release of growth factors has been investigated to sustain their effects for blood vessel formation. 38, 39 In scaffold-based tissue engineering, many researchers have incorporated growth factors in the polymer scaffolds. Growth factors are simply mixed within both hard porous materials, as well as soft gel materials, and biodegradation of the scaffold causes the slow release of the incorporated growth factors.…”

Section: Microfabrication Technologies For Fabricating In Vitro Vascumentioning

confidence: 99%

Cell Sheet-Based Tissue Engineering for Fabricating 3-Dimensional Heart Tissues

Shimizu

2014

Circ J

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“…122 The presentation mode of GFs is a critical step for the generation of a specific tissue response, and several studies have focused on the evaluation of the effect of immobilization technique on cellular response. [123][124][125][126][127][128][129][130][131] For example, it is reported that soluble VEGF induces endothelial cell proliferation, while matrix-bound VEGF promotes vascular sprouting and branching 132 despite other studies revealing opposite responses. 86,130,133,134 Moreover, sustained activation of the Smad intracellular signaling pathway is stimulated upon culture of osteoblastic cells on immobilized BMP-2 due to prolonged phosphorylation of Smad 1/5/8 by In vivo critical-size defects.…”

Section: Single Gf Deliverymentioning

confidence: 99%

“…126 The combined release of BMP-2 and VEGF is commonly approached with mixed results, and control over amount and timing of GF delivery is critical. VEGF dosage must be tightly controlled as excessive amounts of this GF can inhibit osteogenesis and cause severe leakage and hypotension.…”

Section: From Single To Multiple Bioactive Factor Delivery For Skeletmentioning

confidence: 99%

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

Santo

Gomes²,

Mano³

et al. 2013

Tissue Engineering Part B: Reviews

102

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The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors.

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Covalent Growth Factor Immobilization Strategies for Tissue Repair and Regeneration

Cited by 161 publications

References 105 publications

Covalent Binding of BMP-2 on Surfaces Using a Self-assembled Monolayer Approach

Covalent Binding of BMP-2 on Surfaces Using a Self-assembled Monolayer Approach

Cell Sheet-Based Tissue Engineering for Fabricating 3-Dimensional Heart Tissues

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

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