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      Osteochondral regenerative engineering: challenges, state-of-the-art and translational perspectives

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          Abstract

          Despite quantum leaps, the biomimetic regeneration of cartilage and osteochondral regeneration remains a major challenge, owing to the complex and hierarchical nature of compositional, structural and functional properties. In this review, an account of the prevailing challenges in biomimicking the gradients in porous microstructure, cells and extracellular matrix (ECM) orientation is presented. Further, the spatial arrangement of the cues in inducing vascularization in the subchondral bone region while maintaining the avascular nature of the adjacent cartilage layer is highlighted. With rapid advancement in biomaterials science, biofabrication tools and strategies, the state-of-the-art in osteochondral regeneration since the last decade has expansively elaborated. This includes conventional and additive manufacturing of synthetic/natural/ECM-based biomaterials, tissue-specific/mesenchymal/progenitor cells, growth factors and/or signaling biomolecules. Beyond the laboratory-based research and development, the underlying challenges in translational research are also provided in a dedicated section. A new generation of biomaterial-based acellular scaffold systems with uncompromised biocompatibility and osteochondral regenerative capability is necessary to bridge the clinical demand and commercial supply. Encompassing the basic elements of osteochondral research, this review is believed to serve as a standalone guide for early career researchers, in expanding the research horizon to improve the quality of life of osteoarthritic patients affordably.

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          3D bioprinting of tissues and organs.

          Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
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            Biodegradable polymers as biomaterials

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              Electrospinning: applications in drug delivery and tissue engineering.

              Despite its long history and some preliminary work in tissue engineering nearly 30 years ago, electrospinning has not gained widespread interest as a potential polymer processing technique for applications in tissue engineering and drug delivery until the last 5-10 years. This renewed interest can be attributed to electrospinning's relative ease of use, adaptability, and the ability to fabricate fibers with diameters on the nanometer size scale. Furthermore, the electrospinning process affords the opportunity to engineer scaffolds with micro to nanoscale topography and high porosity similar to the natural extracellular matrix (ECM). The inherently high surface to volume ratio of electrospun scaffolds can enhance cell attachment, drug loading, and mass transfer properties. Various materials can be electrospun including: biodegradable, non-degradable, and natural materials. Electrospun fibers can be oriented or arranged randomly, giving control over both the bulk mechanical properties and the biological response to the scaffold. Drugs ranging from antibiotics and anticancer agents to proteins, DNA, and RNA can be incorporated into electrospun scaffolds. Suspensions containing living cells have even been electrospun successfully. The applications of electrospinning in tissue engineering and drug delivery are nearly limitless. This review summarizes the most recent and state of the art work in electrospinning and its uses in tissue engineering and drug delivery.
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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
                26 December 2022
                26 December 2022
                : 10
                : rbac109
                Affiliations
                Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center , Farmington, CT 06030, USA
                Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center , Farmington, CT 06030, USA
                Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center , Farmington, CT 06030, USA
                Department of Orthopaedic Surgery, University of Connecticut Health Center , Farmington, CT 06030, USA
                Department of Chemical and Biomolecular Engineering, University of Connecticut , Storrs, CT 06269, USA
                Department of Biomedical Engineering, University of Connecticut , Storrs, CT 06269, USA
                Department of Materials Science and Engineering, University of Connecticut , Storrs, CT 06269, USA
                Author notes
                Correspondence address. Tel: +1 860 697 4086, E-mail: laurencin@ 123456uchc.edu
                Author information
                https://orcid.org/0000-0001-6765-3047
                Article
                rbac109
                10.1093/rb/rbac109
                9845524
                36683736
                9b6a4b1a-37de-4199-b6aa-5d4a2f924a12
                © The Author(s) 2022. 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
                : 21 October 2022
                : 22 November 2022
                : 09 December 2022
                : 17 January 2023
                Page count
                Pages: 23
                Funding
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Funded by: National Institute of Arthritis and Musculoskeletal and Skin Diseases, DOI 10.13039/100000069;
                Award ID: T32AR079114
                Funded by: BUilding Infrastructure Leading to Diversity;
                Award ID: TL4GM118971
                Categories
                Review
                AcademicSubjects/MED00010
                AcademicSubjects/SCI01410

                osteochondral regeneration,additive manufacturing,gradient porosity,in vivo,commercialization

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