Development of a centrally vascularized tissue engineering bone graft with the unique core-shell composite structure for large femoral bone defect treatment

Wang, Le; Zhu, Lixin; Wang, Zhao; Lou, Aiju; Yang, Yixi; Guo, Yuan; Liu, Song; Zhang, Chi; Zhang, Zheng; Hu, Hansheng; Yang, Bo; Zhang, Ping; Ouyang, Hongwei; Zhang, Zhiyong

doi:10.1016/j.biomaterials.2018.05.017

Cited by 52 publications

(37 citation statements)

References 52 publications

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“…The 10 ng group exhibited significantly more vascular network formation than the other groups both in the central and peripheral regions. This finding was likely observed because the osteogenic and angiogenic processes are highly interdependent during bone defect repair 6 . Immunomodulation properties were subsequently compared among the groups treated with different IL-4 doses via immunofluorescence and immunohistochemistry analyses.…”

Section: Discussionmentioning

confidence: 94%

“…Typical screening of such material involves in vitro and in vivo experiments to investigate biomaterial attributes, including biocompatibility and bioactivity. In addition, many strategies have been developed to optimize the material composition, 3D architecture and mechanical properties to improve its biological performance 1 , 4 - 6 . However, more recently, increasing evidence has demonstrated that the host immune reaction following implantation of bone substitute material determines the success of bone regeneration 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

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Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis

et al. 2018

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Background: Treatment of large bone defects represents a major clinical problem worldwide. Suitable bone substitute materials are commonly required to achieve successful bone regeneration, and much effort has been spent to optimize their chemical compositions, 3D architecture and mechanical properties. However, material-immune system interactions are increasingly being recognized as a crucial factor influencing regeneration. Here, we envisioned an accurate and proactive immunomodulation strategy via delivery of IL-4 (key regulator of macrophage polarization) to promote bone substitute material-mediated regeneration.Methods: Four different IL-4 doses (0 ng, 10 ng, 50 ng and 100 ng) were delivered into rat large cranial bone defects at day 3 post-operation of decellularized bone matrix (DBM) material implantation, and the osteogenesis, angiogenesis and macrophage polarization were meticulously evaluated.Results: Micro-CT analysis showed that immunomodulation with 10 ng IL-4 significantly outperformed the other groups in terms of new bone formation (1.23-5.05 fold) and vascularization (1.29-6.08 fold), achieving successful defect bridging and good vascularization at 12 weeks. Histological analysis at 7 and 14 days showed that the 10 ng group generated the most preferable M1/M2 macrophage polarization profile, resulting in a pro-healing microenvironment with more IL-10 and less TNF-α secretion, a reduced apoptosis level in tissues around the materials, and enhanced mesenchymal stem cell migration and osteogenic differentiation. Moreover, in vitro studies revealed that M1 macrophages facilitated mesenchymal stem cell migration, while M2 macrophages significantly increased cell survival, proliferation and osteogenic differentiation, explaining the in vivo findings.Conclusions: Accurate immunomodulation via IL4 delivery significantly enhanced DBM-mediated osteogenesis and angiogenesis via the coordinated involvement of M1 and M2 macrophages, revealing the promise of this accurate and proactive immunomodulatory strategy for developing new bone substitute materials.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis

et al. 2018

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“…The problem of inadequate vascularization can stem from using allografts that are slower in healing in the initial phase of implantation, with ingrowths possible before the blood vessels of the host come into contact with the implanted scaffold [124]. The larger the bone defect, the more likely vascularization problems are to occur, as a larger blood supply is required in the implant [7]. However, even with the best scaffold, vascularization, along with mechanical strength, can still be improved through the addition of factors mimicking all aspects of bones, including their mechanical, biological, mass transport and microstructure geometry properties [3].…”

Section: Three-dimensionally Printing Scaffoldsmentioning

confidence: 99%

“…Another method that has been developed to help vascularization is tissue engineered scaffolds with a core-shell composite structure (centrally vascularized tissue engineering bone grafts; CV-TEBG) [7]. Made up of an angiogenic core and an osteogenic shell, the core-shell is designed to quickly establish itself in the vascular network and prevent central necrosis [7,123]. CV-TEBG uses a co-culture of mesenchymal stem cells and endothelial progenitor cells in collagen hydrogels that enhances angiogenesis and vascularization in the tissue core.…”

Section: Cv-tebg and Nanotechnology-related Scaffoldsmentioning

confidence: 99%

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Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials

Hutchings

Moncrieff

Dompe

et al. 2020

JCM

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The deterioration of the human skeleton’s capacity for self-renewal occurs naturally with age. Osteoporosis affects millions worldwide, with current treatments including pharmaceutical agents that target bone formation and/or resorption. Nevertheless, these clinical approaches often result in long-term side effects, with better alternatives being constantly researched. Mesenchymal stem cells (MSCs) derived from bone marrow and adipose tissue are known to hold therapeutic value for the treatment of a variety of bone diseases. The following review summarizes the latest studies and clinical trials related to the use of MSCs, both individually and combined with other methods, in the treatment of a variety of conditions related to skeletal health. For example, some of the most recent works noted the advantage of bone grafts based on biomimetic scaffolds combined with MSC and growth factor delivery, with a greatly increased regeneration rate and minimized side effects for patients. This review also highlights the continuing research into the mechanisms underlying bone homeostasis, including the key transcription factors and signalling pathways responsible for regulating the differentiation of osteoblast lineage. Paracrine factors and specific miRNAs are also believed to play a part in MSC differentiation. Furthering the understanding of the specific mechanisms of cellular signalling in skeletal remodelling is key to incorporating new and effective treatment methods for bone disease.

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Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

Armiento

Hatt

Rosenberg

et al. 2020

Adv Funct Materials

134

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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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Development of a centrally vascularized tissue engineering bone graft with the unique core-shell composite structure for large femoral bone defect treatment

Cited by 52 publications

References 52 publications

Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis

Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis

Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials

Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

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