VEGF-mediated angiogenesis and vascularization of a fumarate-crosslinked polycaprolactone (PCLF) scaffold

Wagner, Eric R.; Parry, Joshua A.; Dadsetan, Mahrokh; Bravo, Dalibel; Riester, Scott M.; Wijnen, André J. van; Yaszemski, Michael J.; Kakar, Sanjeev

doi:10.1080/03008207.2018.1424145

Cited by 25 publications

(15 citation statements)

References 34 publications

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“…Ex vivo analysis can either be performed using histological sections in combination with immunolabeling of endothelial cell markers 8,9 , corrosion casts 10,11 , advanced microscopic techniques, such as e.g. confocal laser scanning microscopy 12 , or microcomputed tomography (MicroCT) combined with radiopaque contrast agents 13 . In vivo techniques include high-frequency ultrasound, optoacoustic imaging, two-photon microscopy and magnetic resonance imaging (MRI) 9,14–22 , and serve as stand-alone analysis methods or can be combined with corresponding ex vivo imaging techniques.…”

Section: Introductionmentioning

confidence: 99%

Novel multimodal MRI and MicroCT imaging approach to quantify angiogenesis and 3D vascular architecture of biomaterials

Woloszyk

Wolint

Becker

et al. 2019

Sci Rep

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Quantitative assessment of functional perfusion capacity and vessel architecture is critical when validating biomaterials for regenerative medicine purposes and requires high-tech analytical methods. Here, combining two clinically relevant imaging techniques, (magnetic resonance imaging; MRI and microcomputed tomography; MicroCT) and using the chorioallantoic membrane (CAM) assay, we present and validate a novel functional and morphological three-dimensional (3D) analysis strategy to study neovascularization in biomaterials relevant for bone regeneration. Using our new pump-assisted approach, the two scaffolds, Optimaix (laminar structure mimicking entities of the diaphysis) and DegraPol (highly porous resembling spongy bone), were shown to directly affect the architecture of the ingrowing neovasculature. Perfusion capacity (MRI) and total vessel volume (MicroCT) strongly correlated for both biomaterials, suggesting that our approach allows for a comprehensive evaluation of the vascularization pattern and efficiency of biomaterials. Being compliant with the 3R-principles (replacement, reduction and refinement), the well-established and easy-to-handle CAM model offers many advantages such as low costs, immune-incompetence and short experimental times with high-grade read-outs when compared to conventional animal models. Therefore, combined with our imaging-guided approach it represents a powerful tool to study angiogenesis in biomaterials.

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Section: Introductionmentioning

confidence: 99%

Novel multimodal MRI and MicroCT imaging approach to quantify angiogenesis and 3D vascular architecture of biomaterials

Woloszyk

Wolint

Becker

et al. 2019

Sci Rep

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“…5), is considered optimal for sufficient vascularization and thus performance of biomaterial implants, that is, 150 ng/0.1 mL implant for 4 weeks. 15,25 Although it is known that VEGF is well suitable for vascularization of biomaterial implants, [11][12][13] angiogenesis in vivo is an interplay of several different growth factors and cytokines, such as fibroblast growth factor, hepatocyte growth factor, and plateletderived growth factor, besides VEGF. 16,56 Polymeric microspheres offer the possibility to encapsulate and release other growth factors as well, and these microspheres can also be incorporated in biomaterial devices intended for implantation in vivo, such as PDMS devices used in this study.…”

Section: Discussionmentioning

confidence: 99%

“…3,5 Several approaches seem feasible, among others coating of the polymeric implants with compounds such as fibrin and plateletrich plasma to mimic the extracellular matrix, or coformulation of proangiogenic growth factors within the device, 9,10 for instance, vascular endothelial growth factor (VEGF). [11][12][13] Proper functional vascularization of the surface of implants, that is, the formation of stable blood vessels that encompass the device, will take around 4 weeks upon implantation, depending on the site of implantation, as shown in rodent models. 10,14,15 We therefore postulate that continuous delivery of VEGF for 3-4 weeks is preferred and that such a sustained release can best be achieved by its encapsulation in a controlled drug delivery system such as microsphere.…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor–Releasing Microspheres Based on Poly(ε-Caprolactone-PEG-ε-Caprolactone)-b-Poly(L-Lactide) Multiblock Copolymers Incorporated in a Three-Dimensional Printed Poly(Dimethylsiloxane) Cell Macroencapsulation Device

Scheiner

Coulter

Maas-Bakker

et al. 2020

Journal of Pharmaceutical Sciences

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Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to prevent rejection of the transplanted islets. Novel approaches therefore have focused on encapsulation of the islets in biomaterial implants which can protect the islets and offer an organ-like environment. Vascularization of the device's surface is a prerequisite for the survival and proper functioning of transplanted pancreatic islets. We are pursuing a prevascularization strategy by incorporation of vascular endothelial growth factor (VEGF)-loaded microspheres in 3-dimensional printed poly(dimethylsiloxane)-based devices prior to their prospective loading with transplanted cells. Microspheres (~50 mm) were based on poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymers and were loaded with 10 mg VEGF/mg microspheres, and subsequently dispersed in a hyaluronic acid carrier liquid. In vitro release studies at 37 C demonstrated continuous release of fully bioactive VEGF for 4 weeks. In conclusion, our results demonstrate that incorporation of VEGF-releasing microspheres ensures adequate release of VEGF for a time window of 4 weeks, which is attractive in view of the vascularization of artificial pancreas implants.

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“…Moreover, many studies have promoted the application of 3D printing technology in cytokine sustained-release by improving processing [62], advancing technology [63] or allowing combinations with other forms of carriers [64]. Up to now, these materials have been successfully used in various tissue and organ regeneration experiments in vitro and in vivo, such as vascular regeneration [65], bone regeneration [63] and skin regeneration [66]. The 4D printing technology is a dynamic and time dependent manufacturing process based on advanced 3D-print features, which providing great potential for tissue and organ engineering applications [67].…”

Section: D Printing Technologymentioning

confidence: 99%

Tooth Regeneration: Insights from Tooth Development and Spatial-Temporal Control of Bioactive Drug Release

Huang

Ren

et al. 2019

Stem Cell Rev and Rep

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Tooth defect and tooth loss are common clinical diseases in stomatology. Compared with the traditional oral restoration treatment, tooth regeneration has unique advantages and is currently the focus of oral biomedical research. It is known that dozens of cytokines/growth factors and other bioactive factors are expressed in a spatial-temporal pattern during tooth development. On the other hand, the technology for spatial-temporal control of drug release has been intensively studied and well developed recently, making control release of these bioactive factors mimicking spatial-temporal pattern more feasible than ever for the purpose of tooth regeneration. This article reviews the research progress on the tooth development and discusses the future of tooth regeneration in the context of spatial-temporal release of developmental factors.

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VEGF-mediated angiogenesis and vascularization of a fumarate-crosslinked polycaprolactone (PCLF) scaffold

Abstract: PCLF polymer scaffold can be utilized as a framework for vascular ingrowth and regeneration of multiple types of tissues. This novel scaffold material has promise in tissue regeneration across all types of tissues from soft tissue to bone.

Cited by 25 publications

References 34 publications

Novel multimodal MRI and MicroCT imaging approach to quantify angiogenesis and 3D vascular architecture of biomaterials

Novel multimodal MRI and MicroCT imaging approach to quantify angiogenesis and 3D vascular architecture of biomaterials

Vascular Endothelial Growth Factor–Releasing Microspheres Based on Poly(ε-Caprolactone-PEG-ε-Caprolactone)-b-Poly(L-Lactide) Multiblock Copolymers Incorporated in a Three-Dimensional Printed Poly(Dimethylsiloxane) Cell Macroencapsulation Device

Tooth Regeneration: Insights from Tooth Development and Spatial-Temporal Control of Bioactive Drug Release

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