Fabrication of viable and functional pre‐vascularized modular bone tissues by coculturing MSCs and HUVECs on microcarriers in spinner flasks

Zhang, Songjie; Zhou, Min; Ye, Zhaoyang; Zhou, Yan; Tan, Wen‐Song

doi:10.1002/biot.201700008

Cited by 28 publications

(15 citation statements)

References 48 publications

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“…Lin et al showed that chondrogenic pellets generated from microcarrier cultures developed larger pellet diameters, and produced more DNA, GAG and collagen II per pellet with greater GAG/DNA and collagen II/DNA ratios compared with that of tissue culture flasks, while similar result were observed by using another type of microcarrier [64]. An increasing number of studies have highlighted bone formation potential by using microcarrier cultures, for example, a new process developed by Zhang et al fabricated pre-vascularized bone microtissues by integrating microcarrier culture and co-culture with MS and HUVEC [65]. Aside from that, Tanimowo et al fabricated a novel agarose-k-casein microsphere which upregulated the expression of osteogenic differentiation markers in bone marrow MSCs [57].…”

Section: Msc Differentiationmentioning

confidence: 57%

Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review

et al. 2020

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Stem cell-based regenerative medicine is a promising approach for tissue reconstruction. However, a large number of cells are needed in a typical clinical study, where conventional monolayer cultures might pose a limitation for scaleup. The purpose of this review was to systematically assess the application of microcarriers in Mesenchymal Stem Cell cultures. A comprehensive search was conducted in Medline via Ebscohost, Pubmed, and Scopus, and relevant studies published between 2015 and 2019 were selected. The literature search identified 53 related studies, but only 14 articles met the inclusion criteria. These include 7 utilised commercially available microcarriers, while the rest were formulated based on different surface characteristics, all of which are discussed in this review. Current applications of microcarriers were focused on MSC expansion and induction of MSCs into different lineages. These studies demonstrated that MSCs could proliferate in a microcarrier culture system in-fold compared to monolayer cultures, and the culture system could simulate a three-dimensional environment which induces cell differentiation. However, detailed studies are still required before this system were to be adapted into the scale of GMP manufacturing.

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Section: Msc Differentiationmentioning

confidence: 57%

Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review

et al. 2020

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“…All the observations here reported suggest that SO scaffolds show promising perspectives in terms of induced pro-angiogenic mechanism and in terms of enhanced osteoblast-like cells and activation of extracellular matrix mineralization processes. Both the capabilities to mimic vascular-like networks and to induce matrix mineralization by cell models are prerequisites to reliably reproduce the bone morphogenetic processes in vitro [ 46 , 47 ]. The differential analyses here performed allow an accurate prediction of the possible behavior of endothelial and osteoblast cells that could be attached to SOs and implanted as 3D-functionalized scaffolds in in vivo critical defects; as a speculative aspect, a possible expected result could be the generation of novel 3D constructs for regenerative medicine.…”

Section: Discussionmentioning

confidence: 99%

Proposal of a Novel Natural Biomaterial, the Scleral Ossicle, for the Development of Vascularized Bone Tissue In Vitro

et al. 2017

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Recovering of significant skeletal defects could be partially abortive due to the perturbations that affect the regenerative process when defects reach a critical size, thus resulting in a non-healed bone. The current standard treatments include allografting, autografting, and other bone implant techniques. However, although they are commonly used in orthopedic surgery, these treatments have some limitations concerning their costs and their side effects such as potential infections or malunions. On this account, the need for suitable constructs to fill the gap in wide fractures is still urgent. As an innovative solution, scleral ossicles (SOs) can be put forward as natural scaffolds for bone repair. SOs are peculiar bony plates forming a ring at the scleral-corneal border of the eyeball of lower vertebrates. In the preliminary phases of the study, these ossicles were structurally and functionally characterized. The morphological characterization was performed by SEM analysis, MicroCT analysis and optical profilometry. Then, UV sterilization was carried out to obtain a clean support, without neither contaminations nor modifications of the bone architecture. Subsequently, the SO biocompatibility was tested in culture with different cell lines, focusing the attention to the differentiation capability of endothelial and osteoblastic cells on the SO surface. The results obtained by the above mentioned analysis strongly suggest that SOs can be used as bio-scaffolds for functionalization processes, useful in regenerative medicine.

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“…After 4 weeks of osteogenic culture inside a spinner flask, the co-cultured MSCs and human umbilical vein endothelial cells (HUVECs) (seeded onto macroporous gelatin beads) formed microtissues with tube formation ability. [371] This approach has not been further evaluated in vivo, therefore it is still unknown if such an approach could improve bone healing, but demonstrates the promise of generating prevascularized microtissues that could be further incorporated into more complex biomaterials to improve its mechanical properties and mimic ECM signaling.…”

Section: Bone Regeneration Approaches In Targeting Vascularizationmentioning

confidence: 99%

“…The same approach of using a sacrificial material was used for the skeletal muscle reconstruction with the difference that PCL pillars were specifically printed and C2C12 myoblasts were used. In vivo results showed enhanced healing abilities of the implanted constructs making this bioprinting approach a promising technology for clinical future applications in [371] Vascularization of engineered bone grafts MSCs a) and HUVEC b) are cultured within spinner flask…”

Section: Bone Regeneration Approaches In Targeting Vascularizationmentioning

confidence: 99%

Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

Armiento

Hatt

Rosenberg

et al. 2020

Adv Funct Materials

154

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Bone is a hard yet dynamic tissue with remarkable healing capacities. Research to date has greatly advanced the understanding of how bone heals and has led to marked success in the treatment of bone injuries. Nevertheless, the effective treatment of nonunions and large bone defects continues to present a challenge for orthopedic surgeons. Biomaterials provide researchers with a powerful instrument to potentially guide effective bone tissue regeneration in challenging healing environments. However, the most appropriate biomaterial for bone tissue engineering continues to be an area of intense debate. Indeed, the mechanical properties of real bone can be reproduced in vitro but the development of a functional bone substitute goes beyond the sole mechanical properties. The faithful reproduction of bone as a functional organ requires the combination of different cell types and temporal regulation of the molecular signaling involved during the different stages of bone formation and regeneration. This is not at all a trivial task. Herein, critical aspects of bone healing/regeneration including mechanical loading, inflammation, vascularization, and innervation are described. The success and the challenges behind the development of biomaterials, and the technologies used to functionalize them, in order to support the underlying cellular mechanisms are also highlighted.

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Fabrication of viable and functional pre‐vascularized modular bone tissues by coculturing MSCs and HUVECs on microcarriers in spinner flasks

Abstract: Collectively, this work established an effective method to fabricate pre-vascularized bone microtissues, which would lay a solid foundation for subsequent development of vascularized tissue grafts for bone regeneration.

Cited by 28 publications

References 48 publications

Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review

Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review

Proposal of a Novel Natural Biomaterial, the Scleral Ossicle, for the Development of Vascularized Bone Tissue In Vitro

Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

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