Mesenchymal Stem Cells: a Modern Approach to Treat Long Bones Defects

Stres, Hana Krečič; Krkovič, Matija; Koder, Jadran; Maličev, Elvira; Marolt, Darja; Drobnič, Matej; Kregar-Velikonja, Nevenka

doi:10.1007/978-3-540-73044-6_63

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…Tissue engineering is a multidisciplinary field that aims to enable repair or regeneration of damaged or diseased tissues using appropriate combinations of cells, biomaterials and instructive signals (Reddi, 1998;Reddi, 2007). Despite decades of research, relatively few bone tissue engineering therapies have reached the clinic and those that have typically report poorer outcomes than in pre-clinical animal www.ecmjournal.org trials (d'Aquino et al, 2009;Hibi et al, 2006;Krecic-Stres et al, 2007;Lee et al, 2010;Marcacci et al, 2007;Meijer et al, 2007;Meijer et al, 2008;Quarto et al, 2001;Shayesteh et al, 2008;Zamiri et al, 2013). Reasons for this are multi-faceted, including poor scaffold mechanical properties, poor implant vascularisation and inadequate new bone formation in vivo (Amini et al, 2012;Ko et al, 2007;Phelps and Garcia, 2009).…”

Section: Introductionmentioning

confidence: 99%

Biofabrication of multiscale bone extracellular matrix scaffolds for bone tissue engineering

Freeman

Browe

Nulty

et al. 2019

eCM

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Interconnected porosity is critical to the design of regenerative scaffolds, as it permits cell migration, vascularisation and diffusion of nutrients and regulatory molecules inside the scaffold. 3D printing is a promising strategy to achieve this as it allows the control over scaffold pore size, porosity and interconnectivity. Thus, the aim of the present study was to integrate distinct biofabrication strategies to develop a multiscale porous scaffold that was not only mechanically functional at the time of implantation, but also facilitated rapid vascularisation and provided stem cells with appropriate cues to enable their differentiation into osteoblasts. To achieve this, polycaprolactone (PCL) was functionalised with decellularised bone extracellular matrix (ECM), to produce osteoinductive filaments for 3D printing. The addition of bone ECM to the PCL not only increased the mechanical properties of the resulting scaffold, but also increased cellular attachment and enhanced osteogenesis of mesenchymal stem cells (MSCs). In vivo, scaffold pore size determined the level of vascularisation, with a larger filament spacing supporting faster vessel in-growth and more new bone formation. By freeze-drying solubilised bone ECM within these 3D-printed scaffolds, it was possible to introduce a matrix network with microscale porosity that further enhanced cellular attachment in vitro and increased vessel infiltration and overall levels of new bone formation in vivo. To conclude, an "off-the-shelf" multiscale bone-ECM-derived scaffold was developed that was mechanically stable and, once implanted in vivo, will drive vascularisation and, ultimately, lead to bone regeneration.

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Section: Introductionmentioning

confidence: 99%

Biofabrication of multiscale bone extracellular matrix scaffolds for bone tissue engineering

Freeman

Browe

Nulty

et al. 2019

eCM

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Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration

Freeman

McNamara

2017

Tissue Engineering Part B: Reviews

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Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for bone tissue graft.

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Tissue Engineered Bone Grafts: Biological Requirements, Tissue Culture and Clinical Relevance

Fröhlich

Grayson

Wan

et al. 2008

CSCR

297

239

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The tremendous need for bone tissue in numerous clinical situations and the limited availability of suitable bone grafts are driving the development of tissue engineering approaches to bone repair. In order to engineer viable bone grafts, one needs to understand the mechanisms of native bone development and fracture healing, as these processes should ideally guide the selection of optimal conditions for tissue culture and implantation. Engineered bone grafts have been shown to have capacity for osteogenesis, osteoconduction, osteoinduction and osteointegration - functional connection between the host bone and the graft. Cells from various anatomical sources in conjunction with scaffolds and osteogenic factors have been shown to form bone tissue in vitro. The use of bioreactor systems to culture cells on scaffolds before implantation further improved the quality of the resulting bone grafts. Animal studies confirmed the capability of engineered grafts to form bone and integrate with the host tissues. However, the vascularization of bone remains one of the hurdles that need to be overcome if clinically sized, fully viable bone grafts are to be engineered and implanted. We discuss here the biological guidelines for tissue engineering of bone, the bioreactor cultivation of human mesenchymal stem cells on three-dimensional scaffolds, and the need for vascularization and functional integration of bone grafts following implantation.

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Mesenchymal Stem Cells: a Modern Approach to Treat Long Bones Defects

Cited by 4 publications

References 10 publications

Biofabrication of multiscale bone extracellular matrix scaffolds for bone tissue engineering

Biofabrication of multiscale bone extracellular matrix scaffolds for bone tissue engineering

Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration

Tissue Engineered Bone Grafts: Biological Requirements, Tissue Culture and Clinical Relevance

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