Stimulation of Angiogenesis by FGF-1 Delivered Through a Modified Fibrin Scaffold

Pandit, Abhay; Feldman, Dale; Caulfield, James; Thompson, Anthony

doi:10.3109/08977199809117187

Cited by 54 publications

(36 citation statements)

References 14 publications

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“…[27][28][29][30] In addition, previous studies developed methods to conjugate growth factors into fibrin hydrogels through the action of FXIII and the fibrin-binding peptide, NQEQVSP. 31 Previously our group has utilized this method to conjugate growth factors, which are then released to the tissues in a cell-controlled manner, thereby increasing the effectiveness of delivery to the local microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation

Yuan

Smith

Guan

et al. 2016

Tissue Engineering Part A

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Bone is a highly vascularized tissue and efficient bone regeneration requires neovascularization, especially for critical-sized bone defects. We developed a novel hybrid biomaterial comprising nanocalcium sulfate (nCS) and fibrin hydrogel to deliver mesenchymal stem cells (MSCs) and angiogenic factors, vascular endothelial growth factor (VEGF) and fibroblast growth factor 9 (FGF9), to promote neovascularization and bone formation. MSC and growth factor(s)-loaded scaffolds were implanted subcutaneously into mice to examine their angiogenic and osteogenic potential. Micro CT, alkaline phosphatase activity assay, and histological analysis were used to evaluate bone formation, while immunohistochemistry was employed to assess neovessel formation. The presence of fibrin preserved the nCS scaffold structure and promoted de novo bone formation. In addition, the presence of bone morphogenic protein 2-expressing MSC in nCS and fibrin hydrogels improved bone regeneration significantly. While FGF9 alone had no significant effect, the combination FGF9 and VEGF conjugated in fibrin enhanced neovascularization and bone formation more than 4-fold compared to nCS with MSC. Overall, our results suggested that the combination of nCS (to support bone formation) with a fibrin-based VEGF/FGF9 release system (support vascular formation) is an innovative and effective strategy that significantly enhanced ectopic bone formation in vivo.

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Section: Introductionmentioning

confidence: 99%

Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation

Yuan

Smith

Guan

et al. 2016

Tissue Engineering Part A

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“…145 Pandit et al used the Image Based Analysis System (IBAS) (formerly sold by Kontron, Eching/Mü nchen, Germany) to quantify contraction, epithelialization, volume fractions of different cell types, and blood vessels on H&E-stained sections. 179,183,185,187,188 This is also possible by using pixel intensities to quantify tissue and fibroblast ingrowth, 200 which can be performed using freely available software like ImageJ (http://rsbweb.nih.gov/ij/).…”

mentioning

confidence: 99%

An Overview of Methods for theIn VivoEvaluation of Tissue-Engineered Skin Constructs

Lammers

Verhaegen

Ulrich

et al. 2011

Tissue Engineering Part B: Reviews

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Cutaneous wounding often leads to contraction and scarring, which may result in a range of functional, cosmetic, and psychological complications. Tissue-engineered skin substitutes are being developed to enhance restoration of the skin and improve the quality of wound healing. The aim of this review is to provide researchers in the field of tissue engineering an overview of the methods that are currently used to clinically evaluate skin wound healing, and methods that are used to evaluate tissue-engineered constructs in animal models. Clinically, the quality of wound healing is assessed by noninvasive subjective scar assessment scales and objective techniques to measure individual scar features. Alternatively, invasive technologies are used. In animal models, most tissue-engineered skin constructs studied are at least evaluated macroscopically and by using conventional histology (hematoxylin-eosin staining). Planimetry and immunohistochemistry are also often applied. An overview of antibodies used is provided. In addition, some studies used methods to assess gene expression levels and mRNA location, transillumination for blood vessel observation, in situ/in vivo imaging, electron microscopy, mechanical strength assessment, and microbiological sampling. A more systematic evaluation of tissue-engineered skin constructs in animal models is recommended to enhance the comparison of different constructs, thereby accelerating the trajectory to application in human patients. This would be further enhanced by the embracement of more clinically relevant objective evaluation methods. In addition, fundamental knowledge on construct-mediated wound healing may be increased by new developments in, for example, gene expression analysis and noninvasive imaging.

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“…This principle has already been shown to be successful in a rabbit ear ulcer model, in which the delivery of FGF-1 through biodegradable fibrin or collagen scaffolds resulted in an enhanced healing process of full-thickness skin defects, as indicated by increased angiogenesis and enhanced epithelialization. 71,72 In general, there are 2 possibilities to incorporate growth factors into synthetic scaffolds. It can be done by simply mixing the growth factor with polymer particles before processing the polymer into a porous scaffold, resulting in a rapid release of the growth factor within days to weeks.…”

Section: Stimulation Of Angiogenesis By Growth Factorsmentioning

confidence: 99%

Angiogenesis in Tissue Engineering: Breathing Life into Constructed Tissue Substitutes

Laschke¹,

Harder²,

Amon³

et al. 2006

Tissue Engineering

128

154

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Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure. To achieve vascularization of tissue constructs, several approaches are currently under investigation. These include the modification of biomaterial properties of scaffolds and the stimulation of blood vessel development and maturation by different growth factors using slow-release devices through pre-encapsulated microspheres. Moreover, new microvascular networks in tissue substitutes can be engineered by using endothelial cells and stem cells or by creating arteriovenous shunt loops. Nonetheless, the currently used techniques are not sufficient to induce the rapid vascularization necessary for an adequate cellular oxygen supply. Thus, future directions of research should focus on the creation of microvascular networks within 3D tissue constructs in vitro before implantation or by co-stimulation of angiogenesis and parenchymal cell proliferation to engineer the vascularized tissue substitute in situ.

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Stimulation of Angiogenesis by FGF-1 Delivered Through a Modified Fibrin Scaffold

Cited by 54 publications

References 14 publications

Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation

Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation

An Overview of Methods for theIn VivoEvaluation of Tissue-Engineered Skin Constructs

Angiogenesis in Tissue Engineering: Breathing Life into Constructed Tissue Substitutes

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