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      Research progress of vascularization strategies of tissue-engineered bone

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          Abstract

          The bone defect caused by fracture, bone tumor, infection, and other causes is not only a problematic point in clinical treatment but also one of the hot issues in current research. The development of bone tissue engineering provides a new way to repair bone defects. Many animal experimental and rising clinical application studies have shown their excellent application prospects. The construction of rapid vascularization of tissue-engineered bone is the main bottleneck and critical factor in repairing bone defects. The rapid establishment of vascular networks early after biomaterial implantation can provide sufficient nutrients and transport metabolites. If the slow formation of the local vascular network results in a lack of blood supply, the osteogenesis process will be delayed or even unable to form new bone. The researchers modified the scaffold material by changing the physical and chemical properties of the scaffold material, loading the growth factor sustained release system, and combining it with trace elements so that it can promote early angiogenesis in the process of induced bone regeneration, which is beneficial to the whole process of bone regeneration. This article reviews the local vascular microenvironment in the process of bone defect repair and the current methods of improving scaffold materials and promoting vascularization.

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          Most cited references131

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          Injectable hydrogels for cartilage and bone tissue engineering

          Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.
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            Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair.

            Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and regeneration; however, the cellular mechanisms by which it works are not fully understood. In this study, we investigated the functions of osteoblast-derived VEGF in healing of a bone defect. The results indicate that osteoblast-derived VEGF plays critical roles at several stages in the repair process. Using transgenic mice with osteoblast-specific deletion of Vegfa, we demonstrated that VEGF promoted macrophage recruitment and angiogenic responses in the inflammation phase, and optimal levels of VEGF were required for coupling of angiogenesis and osteogenesis in areas where repair occurs by intramembranous ossification. VEGF likely functions as a paracrine factor in this process because deletion of Vegfr2 in osteoblastic lineage cells enhanced osteoblastic maturation and mineralization. Furthermore, osteoblast- and hypertrophic chondrocyte-derived VEGF stimulated recruitment of blood vessels and osteoclasts and promoted cartilage resorption at the repair site during the periosteal endochondral ossification stage. Finally, osteoblast-derived VEGF stimulated osteoclast formation in the final remodeling phase of the repair process. These findings provide a basis for clinical strategies to improve bone regeneration and treat defects in bone healing.
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              The roles of vascular endothelial growth factor in bone repair and regeneration.

              Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1918230/overviewRole: Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1300901/overviewRole: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1709022/overviewRole: Role: Role: Role: Role:
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                19 January 2024
                2023
                : 11
                : 1291969
                Affiliations
                [1] 1 Department of Orthopedic Surgery , The First Affiliated Hospital of Soochow University , Suzhou, Jiangsu, China
                [2] 2 Department of Orthopedic Surgery , The Second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University , Lianyungang, Jiangsu, China
                [3] 3 Department of Orthopedic Surgery , The Affiliated Lianyungang Clinical College of Xuzhou Medical University , Lianyungang, Jiangsu, China
                [4] 4 Department of Orthopedic Surgery , The Affiliated Lianyungang Clinical College of Jiangsu University , Lianyungang, Jiangsu, China
                Author notes

                Edited by: Junxi Wu, University of Strathclyde, United Kingdom

                Reviewed by: Ayan Samanta, Uppsala University, Sweden

                Jaydee Cabral, University of Otago, New Zealand

                *Correspondence: Zhonglai Qian, qzldoctor@ 123456163.com ; Xuzhu Gao, alexgwan@ 123456163.com ; Mingming Liu, drliumingming@ 123456163.com
                [ † ]

                These authors have contributed equally to this work

                Article
                1291969
                10.3389/fbioe.2023.1291969
                10834685
                38312513
                de282e58-d1e0-414f-8db2-16731af10e9d
                Copyright © 2024 Lv, Zhou, Hou, Hong, Li, Qian, Gao and Liu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 September 2023
                : 06 December 2023
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 82274558), Lianyungang Traditional Chinese Medicine Technology Development Plan Project (ZD202210), Lianyungang Key Science and Technology Research and Development Plan (No. SF2206), and Research Foundation of Kangda College of Nanjing Medical University (No. KD2022KYJJZD035).
                Categories
                Bioengineering and Biotechnology
                Review
                Custom metadata
                Tissue Engineering and Regenerative Medicine

                osteogenesis,bone tissue engineering,bone defect,biological materials,angiogenesis

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