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      3D-printed porous functional composite scaffolds with polydopamine decoration for bone regeneration

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          Abstract

          Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately. 3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration. Inspired by the spongy structure of natural bone, novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone (PLCL) and bioactive glass 45S5 (BG), and polydopamine (PDA) was used to decorate the PLCL/BG scaffolds. The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured, and their osteogenic and angiogenic effects were characterized through a series of experiments both in vitro and in vivo. The results show that the PLCL/BG2/PDA scaffold possessed a good compression modulus and brilliant hydrophilicity. The proliferation, adhesion and osteogenesis of hBMSCs were improved in the PDA coating groups, which exhibited the best performance. The results of the SD rat cranium defect model indicate that PLCL/BG2/PDA obviously promoted osteointegration, which was further confirmed through immunohistochemical staining. Therefore, PDA decoration and the sustained release of bioactive ions (Ca, Si, P) from BG in the 3D-printed PLCL/BG2/PDA scaffold could improve surface bioactivity and promote better osteogenesis and angiogenesis, which may provide a valuable basis for customized implants in extensive bone defect repair applications.

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          Polydopamine and its derivative materials: synthesis and promising applications in energy, environmental, and biomedical fields.

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            Porosity of 3D biomaterial scaffolds and osteogenesis.

            Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be approximately 100 microm due to cell size, migration requirements and transport. However, pore sizes >300 microm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vascularization, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs.
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              A 3D bioprinting system to produce human-scale tissue constructs with structural integrity

              A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.
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                Author and article information

                Contributors
                Journal
                Regen Biomater
                Regen Biomater
                rb
                Regenerative Biomaterials
                Oxford University Press
                2056-3418
                2056-3426
                2023
                21 June 2023
                21 June 2023
                : 10
                : rbad062
                Affiliations
                Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, P. R. China
                Joint Centre of Translational Medicine, Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences , Wenzhou, Zhejiang 325011, P. R. China
                University of Chinese Academy of Sciences , Beijing 100049, P. R. China
                Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, P. R. China
                Joint Centre of Translational Medicine, Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences , Wenzhou, Zhejiang 325011, P. R. China
                Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, P. R. China
                Joint Centre of Translational Medicine, Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences , Wenzhou, Zhejiang 325011, P. R. China
                The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, P. R. China
                Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, P. R. China
                Joint Centre of Translational Medicine, Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences , Wenzhou, Zhejiang 325011, P. R. China
                The Affiliated Xiangshan Hospital of Wenzhou Medical University , Ningbo, Zhejiang 315700, P. R. China
                Department of Chemistry and Polymer Science, Stellenbosch University , Matieland, Stellenbosch 7602, South Africa
                Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, P. R. China
                Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, P. R. China
                Joint Centre of Translational Medicine, Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences , Wenzhou, Zhejiang 325011, P. R. China
                Author notes
                Correspondence address. E-mail: lihq@ 123456ucas.ac.cn (H.L.); zcw6681@ 123456126.com (C.Z.)
                Author information
                https://orcid.org/0000-0002-6151-6479
                Article
                rbad062
                10.1093/rb/rbad062
                10374492
                37520855
                fa533615-640f-4d11-91bd-9ad0ae858a8d
                © The Author(s) 2023. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 February 2023
                : 30 April 2023
                : 14 June 2023
                : 27 July 2023
                Page count
                Pages: 15
                Funding
                Funded by: Wenzhou Institute, University of Chinese Academy of Sciences, DOI 10.13039/501100013910;
                Award ID: WIUCASQD2019002
                Award ID: WIUCASZZXF21005
                Categories
                Research Article
                AcademicSubjects/MED00010
                AcademicSubjects/SCI01410

                3d printing,bioactive glass composites,polydopamine,angiogenesis,bone regeneration

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