Enhancing the biological performance of synthetic polymeric materials by decoration with engineered, decellularized extracellular matrix

Sadr, Nasser; Pippenger, Benjamin E.; Scherberich, Arnaud; Wendt, David; Mantero, Sara; Martin, Ivan; Papadimitropoulos, Adam

doi:10.1016/j.biomaterials.2012.03.082

Cited by 111 publications

(95 citation statements)

References 51 publications

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“…This feature, recognized thanks to the use of a model upscaled in size, suggests the possible use of engineered hypertrophic cartilage as a surrogate of fracture callus, in pathologies where this does not form efficiently (e.g., atrophic nonunions). Moreover, the recruitment of resident cells for bone formation at the implant periphery warrants further investigations on the nature of the delivered instructive signals, which could develop the perspective of engineering decellularized ECMs based on hypertrophic cartilage to induce endogenous regeneration of bone tissue (23).…”

Section: Discussionmentioning

confidence: 99%

Engineering of a functional bone organ through endochondral ossification

Scotti

Piccinini

Takizawa

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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279

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Embryonic development, lengthening, and repair of most bones proceed by endochondral ossification, namely through formation of a cartilage intermediate. It was previously demonstrated that adult human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) can execute an endochondral program and ectopically generate mature bone. Here we hypothesized that hMSCs pushed through endochondral ossification can engineer a scaled-up ossicle with features of a "bone organ," including physiologically remodeled bone, mature vasculature, and a fully functional hematopoietic compartment. Engineered hypertrophic cartilage required IL-1β to be efficiently remodeled into bone and bone marrow upon subcutaneous implantation. This model allowed distinguishing, by analogy with bone development and repair, an outer, cortical-like perichondral bone, generated mainly by host cells and laid over a premineralized area, and an inner, trabecular-like, endochondral bone, generated mainly by the human cells and formed over the cartilaginous template. Hypertrophic cartilage remodeling was paralleled by ingrowth of blood vessels, displaying sinusoid-like structures and stabilized by pericytic cells. Marrow cavities of the ossicles contained phenotypically defined hematopoietic stem cells and progenitor cells at similar frequencies as native bones, and marrow from ossicles reconstituted multilineage long-term hematopoiesis in lethally irradiated mice. This study, by invoking a "developmental engineering" paradigm, reports the generation by appropriately instructed hMSC of an ectopic "bone organ" with a size, structure, and functionality comparable to native bones. The work thus provides a model useful for fundamental and translational studies of bone morphogenesis and regeneration, as well as for the controlled manipulation of hematopoietic stem cell niches in physiology and pathology.

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Section: Discussionmentioning

confidence: 99%

Engineering of a functional bone organ through endochondral ossification

Scotti

Piccinini

Takizawa

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

279

295

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“…Researchers utilize a variety of scaffolds to study the behavior of MSCs in 3D cultures. [29][30][31][32][33][34] Typically, these 3D scaffolds are composed of foreign materials (either natural or synthetic) and often elicit an atypical cellular response. Therefore, to study the behavior of MSCs in vitro, an ideal 3D environment should be composed of materials that mimic the native tissue.…”

Section: Introductionmentioning

confidence: 99%

Stromal-Cell-Derived Extracellular Matrix Promotes the Proliferation and Retains the Osteogenic Differentiation Capacity of Mesenchymal Stem Cells on Three-Dimensional Scaffolds

Antebi

Zhang

Wang

et al. 2015

Tissue Engineering Part C: Methods

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To date, expansion of bone-marrow-derived mesenchymal stem cells (MSCs) is typically carried out on twodimensional (2D) tissue culture plastic. Since this 2D substratum is very different from the physiological situation, MSCs gradually lose their unique multipotent properties during expansion. Recently, the role of the extracellular matrix (ECM) microenvironment (''niche'') in facilitating and regulating stem cell behavior in vivo has been elucidated. As a result, investigators have shifted their efforts toward developing threedimensional (3D) scaffolds capable of functioning like the native tissue ECM. In this study, we demonstrated that stromal-cell-derived ECM, formed within a collagen/hydroxyapatite (Col/HA) scaffold to mimic the bone marrow ''niche,'' promoted MSC proliferation and preserved their differentiation capacity. The ECM was synthesized by MSCs to reconstitute the tissue-specific 3D microenvironment in vitro. Following deposition of the ECM inside Col/HA scaffold, the construct was decellularized and reseeded with MSCs to study their behavior. The data showed that MSCs cultured on the ECM-Col/HA scaffolds grew significantly faster than the cells from the same batch cultured on the regular Col/HA scaffolds. In addition, MSCs cultured on the ECMCol/HA scaffolds retained their ''stemness'' and osteogenic differentiation capacity better than MSCs cultured on regular Col/HA scaffolds. When ECM-Col/HA scaffolds were implanted into immunocompromised mice, with or without loading MSCs, it was found that those scaffolds formed less bone as compared with regular Col/ HA scaffolds (i.e., without ECM), in both cases of with or without loading MSCs. The in vivo study further confirmed that the ECM-Col/HA scaffold was a suitable mimic of the bone marrow ''niche.'' This novel 3D stromal-cell-derived ECM system has the potential to be developed into a biomedical platform for regenerative medicine applications.

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“…Besides the widely studied ECM scaffolds derived from animal tissues or organs, the ECM scaffolds fabricated from cultured cells have gained increased interest. [3][4][5][6] Compared with animal tissues, cell-derived ECM avoids the risk of pathogen transfer caused by allogenic ECM and adverse host immune response caused by xenogenic ECM. 7 In addition, different cell types could be used to fabricate different types of ECM that provide various sets of functional biological signals.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Several studies have shown that there is superiority for the application of cell-derived ECM as a scaffold. 4,5,10 The cell-derived ECM can significantly enhance cell adhesion, migration, proliferation, and acquisition of in vivo-like morphology compared with reconstituted ECM. 11 Decellularized ECM synthesized by undifferentiated mesenchymal stem cells (MSCs) in vitro has been shown to facilitate cell proliferation, prevent spontaneous differentiation, and enhance the chondrogenic and osteogenic potential of freshly reseeded MSCs.…”

Section: Introductionmentioning

confidence: 99%

Decellularization of Fibroblast Cell Sheets for Natural Extracellular Matrix Scaffold Preparation

Xing

Yates

Tahtinen

et al. 2015

Tissue Engineering Part C: Methods

176

134

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The application of cell-derived extracellular matrix (ECM) in tissue engineering has gained increasing interest because it can provide a naturally occurring, complex set of physiologically functional signals for cell growth. The ECM scaffolds produced from decellularized fibroblast cell sheets contain high amounts of ECM substances, such as collagen, elastin, and glycosaminoglycans. They can serve as cell adhesion sites and mechanically strong supports for tissue-engineered constructs. An efficient method that can largely remove cellular materials while maintaining minimal disruption of ECM ultrastructure and content during the decellularization process is critical. In this study, three decellularization methods were investigated: high concentration (0.5 wt%) of sodium dodecyl sulfate (SDS), low concentration (0.05 wt%) of SDS, and freeze-thaw cycling method. They were compared by characterization of ECM preservation, mechanical properties, in vitro immune response, and cell repopulation ability of the resulted ECM scaffolds. The results demonstrated that the high SDS treatment could efficiently remove around 90% of DNA from the cell sheet, but significantly compromised their ECM content and mechanical strength. The elastic and viscous modulus of the ECM decreased around 80% and 62%, respectively, after the high SDS treatment. The freeze-thaw cycling method maintained the ECM structure as well as the mechanical strength, but also preserved a large amount of cellular components in the ECM scaffold. Around 88% of DNA was left in the ECM after the freeze-thaw treatment. In vitro inflammatory tests suggested that the amount of DNA fragments in ECM scaffolds does not cause a significantly different immune response. All three ECM scaffolds showed comparable ability to support in vitro cell repopulation. The ECM scaffolds possess great potential to be selectively used in different tissue engineering applications according to the practical requirement.

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Enhancing the biological performance of synthetic polymeric materials by decoration with engineered, decellularized extracellular matrix

Cited by 111 publications

References 51 publications

Engineering of a functional bone organ through endochondral ossification

Engineering of a functional bone organ through endochondral ossification

Stromal-Cell-Derived Extracellular Matrix Promotes the Proliferation and Retains the Osteogenic Differentiation Capacity of Mesenchymal Stem Cells on Three-Dimensional Scaffolds

Decellularization of Fibroblast Cell Sheets for Natural Extracellular Matrix Scaffold Preparation

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