Bioluminescent and micro-computed tomography imaging of bone repair induced by fibrin-binding growth factors

Vila, Olaia F.; Martino, Mikaël M.; Nebuloni, Laura; Kuhn, Gisela; Pérez‐Amodio, Soledad; Müller, Ralph; Hubbell, Jeffrey A.; Rubio, Núria; Blanco, Jerónimo

doi:10.1016/j.actbio.2014.05.028

Cited by 22 publications

(26 citation statements)

References 41 publications

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“…Vila et al also used fibrin glue for the controlled delivery of an engineered form of PDGF and BMP-2 to enhance bone and vasculature formation in mouse calvarial defects. 177 The same approach is involved in the delivery of parathyroid hormone (PTH1-34) which increases bone turnover via a direct and indirect effect on osteoblasts and osteoclasts. In a study by Arrighi et al, 178 an inactive prodrug TG-pl-PTH1-34 was immobilized to fibrin as in the case of TG-pl-BMP-2 (see section BMP delivery).…”

mentioning

confidence: 99%

A review of fibrin and fibrin composites for bone tissue engineering

Noori

Ashrafi

Vaez-Ghaemi

et al. 2017

IJN

368

256

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Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.

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mentioning

confidence: 99%

A review of fibrin and fibrin composites for bone tissue engineering

Noori

Ashrafi

Vaez-Ghaemi

et al. 2017

IJN

368

256

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“…Boundary condition at the distal layer was adapted from the experimental release kinetics data, and the surrounding tissue was modeled as infinite sink PDGF-BB, which has a low affinity for fibrin within the porous structure. 35,36 Hence, it was assumed that PDGF-BB did not interact with the scaffold. The effective diffusion coefficient within the scaffold was calculated by fitting the model to experimental results to account for both steric effects of the scaffold structure and any binding to fibrin.…”

Section: Methodsmentioning

confidence: 99%

Computational Model-Based Analysis of Strategies to Enhance Scaffold Vascularization

Bayrak

Akar

Somo

et al. 2016

BioResearch Open Access

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Stable and extensive blood vessel networks are required for cell function and survival in engineered tissues. A number of different strategies are currently being investigated to enhance biomaterial vascularization with screening primarily through extensive in vitro and in vivo experiments. In this article, we describe an agent-based model (ABM) developed to evaluate various strategies in silico, including design of optimal biomaterial structure, delivery of angiogenic factors, and application of prevascularized biomaterials. The model predictions are evaluated using experimental data. The ABM developed provides insight into different strategies currently applied for scaffold vascularization and will enable researchers to rapidly screen new hypotheses and explore alternative strategies for enhancing vascularization.

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“…MSCs have long been recognized as clinically relevant cells for bone applications due to their ability to differentiate down an osteogenic lineage not only in vitro, as is widely known, but also in vivo [65]. Vila et al demonstrated, using a dual-luciferase tracking system in which MSCs were transduced to express luciferase driven by constitutive and osteocalcin (OC)-responsive promoters, that MSCs implanted into calvarial defects in mice greatly upregulated their expression of osteocalcin, a late-marker for osteogenic differentiation [66]. In addition to their osteogenic capabilities, the ability to isolate MSCs from either bone marrow or adipose tissue, their immunosuppressive phenotype and the potential for utilization in autologous therapies make these cells alluring for both clinicians and researchers [67, 68].…”

Section: Current Strategies For Vascularization and Bone Regeneratmentioning

confidence: 99%

“…Nevertheless, this endothelial potential does not seem evident when these cells are implanted within a bone defect. In the same study showing positive osteocalcin expression of MSCs, Vila et al also transduced MSCs to express a luciferase-dependent promoter for PECAM1, an endothelial-specific marker, and observed a decrease in PECAM1 expression when MSCs were implanted within a bone defect but an increased expression when implanted intra-muscularly denoting how the microenvironmental cues influence the fate of implanted cells [66]. Although MSCs do not themselves differentiate down an endothelial lineage when implanted in a bone defect, they appear to aid in recruiting endogenous endothelial cells to begin vascular repair [76].…”

Section: Current Strategies For Vascularization and Bone Regeneratmentioning

confidence: 99%

“…Various groups have shown that within one week after orthotopic transplantation, there is a significant loss of cells [66, 165–168]. Additionally, histological analysis up to 4 weeks post implantation shows no presence of transplanted MSC markers indicating that much of the healing response imparted by the delivered cells is limited to transient paracrine signaling [167, 169].…”

Section: Engineering Biomaterials For Enhancing Vascularization Inmentioning

confidence: 99%

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