Chemically-Conjugated Bone Morphogenetic Protein-2 on Three-Dimensional Polycaprolactone Scaffolds Stimulates Osteogenic Activity in Bone Marrow Stromal Cells

Zhang, Huina; Migneco, Francesco; Lin, Chih‐Yuan; Hollister, Scott J.

doi:10.1089/ten.tea.2010.0132

Cited by 89 publications

(70 citation statements)

References 27 publications

(38 reference statements)

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“…This binding may trigger biochemical reactions that change cell function and behavior and finally increase cell proliferation and differentiation. 21 ALP and OPN staining was used as a biochemical marker to determine the osteoblastic phenotype. The BMP-2-loaded scaffolds showed intense staining after 7 days compared with that of the PCL-Gel-BCP scaffolds.…”

Section: Discussionmentioning

confidence: 99%

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In VitroandIn VivoStudies of BMP-2-Loaded PCL–Gelatin–BCP Electrospun Scaffolds

Kim

Linh

Min

et al. 2014

Tissue Engineering Part A

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To confirm the effect of recombinant human bone morphogenetic protein-2 (BMP-2) for bone regeneration, BMP-2-loaded polycaprolactone (PCL)-gelatin (Gel)-biphasic calcium phosphate (BCP) fibrous scaffolds were fabricated using the electrospinning method. The electrospinning process to incorporate BCP nanoparticles into the PCL-Gel scaffolds yielded an extracellular matrix-like microstructure that was a hybrid system composed of nano-and micro-sized fibers. BMP-2 was homogeneously loaded on the PCL-Gel-BCP scaffolds for enhanced induction of bone growth. BMP-2 was initially released at high levels, and then showed sustained release behavior for 31 days. Compared with the PCL-Gel-BCP scaffold, the BMP-2-loaded PCL-Gel-BCP scaffold showed improved cell proliferation and cell adhesion behavior. Both scaffold types were implanted in rat skull defects for 4 and 8 weeks to evaluate the biological response under physiological conditions. Remarkable bone regeneration was observed in the BMP-2/PCL-Gel-BCP group. These results suggest that BMP-2-loaded PCL-Gel-BCP scaffolds should be considered for potential bone tissue engineering applications.

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Section: Discussionmentioning

confidence: 99%

“…21 Natural ECM is composed of fibrous collagen organized in a three-dimensional porous network, and hydroxyapatite (HAp) crystals are dispersed within the collagen fibers. 22 In this study, biphasic calcium phosphate (BCP) nanoparticles were dispersed into a PCL-Gel blend matrix to synthesize a bone mimicking ECM.…”

mentioning

confidence: 99%

In VitroandIn VivoStudies of BMP-2-Loaded PCL–Gelatin–BCP Electrospun Scaffolds

Kim

Linh

Min

et al. 2014

Tissue Engineering Part A

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show abstract

“…163,164 The loading of BMP-2 in scaffold biomaterials CaP, tricalcium phosphate, and PCL increased bone formation. [165][166][167][168] Release pattern of BMP-2 from scaffolds is recognized to be important and scaffold geometry has been used to achieve gradient release of BMP-2.…”

Section: Control Of Growth Factor Release In Scaffoldsmentioning

confidence: 99%

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Chen

Crawford

Chen

et al. 2013

Tissue Engineering Part B: Reviews

206

161

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Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway. MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

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“…Chemical conjugation of growth factors to a scaffold creates functionalized nanofiber scaffolds with tunable growth factor release and a prolonged influence on cell behavior 25,26 . Previously, electrospun scaffolds with chemically conjugated growth factors have been used to encourage neuronal differentiation, enhance wound healing, and stimulate osteogenic cellular activity [27][28][29] .…”

Section: Introductionmentioning

confidence: 99%

^{Hierarchically Structured Electrospun Scaffolds with Chemically Conjugated Growth Factor for Ligament Tissue Engineering}

Sathy

Olvera

McCarthy

et al. 2017

Tissue Engineering Part A

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The anterior cruciate ligament (ACL) of the knee is vital for proper joint function and is commonly ruptured during sports injuries or car accidents. Due to a lack of intrinsic healing capacity and drawbacks with allografts and autografts, there is a need for a tissue engineered ACL replacement. Our group has previously used aligned sheets of electrospun polycaprolactone nanofibers to develop solid cylindrical bundles of longitudinally aligned nanofibers. We have shown that these nanofiber bundles support cell proliferation and elongation and the hierarchical structure and material properties are similar to the native human ACL. It is possible to combine multiple nanofiber bundles to create a scaffold that attempts to mimic the macro-scale structure of the ACL. The goal of this work was to develop a hierarchical bioactive scaffold for ligament tissue engineering using connective tissue growth factor (CTGF) conjugated nanofiber bundles and evaluate the behavior of mesenchymal stem cells (MSCs) on these scaffolds in vitro and in vivo. CTGF was immobilized onto the surface of individual nanofiber bundles or scaffolds consisting of multiple nanofiber bundles. The conjugation efficiency and the release of conjugated CTGF was assessed using X-ray photoelectron spectroscopy, assays, and immunofluorescence staining. Scaffolds were seeded with MSCs and maintained in vitro for 7 days (individual nanofiber bundles), in vitro for 21 days (scaled-up scaffolds of 20 nanofiber bundles) or in vivo for 6 weeks (small scaffolds of 4 nanofiber bundles) and ligament specific tissue formation was assessed in comparison to non-CTGF conjugated control scaffolds. Results showed that CTGF conjugation encouraged cell proliferation and ligament specific tissue formation in vitro and in vivo. The results suggest that hierarchical electrospun nanofiber bundles conjugated with CTGF are a scalable and bioactive scaffold for ACL tissue engineering.

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Chemically-Conjugated Bone Morphogenetic Protein-2 on Three-Dimensional Polycaprolactone Scaffolds Stimulates Osteogenic Activity in Bone Marrow Stromal Cells

Cited by 89 publications

References 27 publications

In VitroandIn VivoStudies of BMP-2-Loaded PCL–Gelatin–BCP Electrospun Scaffolds

In VitroandIn VivoStudies of BMP-2-Loaded PCL–Gelatin–BCP Electrospun Scaffolds

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

^{Hierarchically Structured Electrospun Scaffolds with Chemically Conjugated Growth Factor for Ligament Tissue Engineering}

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