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      Optimizing the composition of gelatin methacryloyl and hyaluronic acid methacryloyl hydrogels to maximize mechanical and transport properties using response surface methodology

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          Abstract

          Hydrogel materials are promising candidates in cartilage tissue engineering as they provide a 3D porous environment for cell proliferation and the development of new cartilage tissue. Both the mechanical and transport properties of hydrogel scaffolds influence the ability of encapsulated cells to produce neocartilage. In photocrosslinkable hydrogels, both of these material properties can be tuned by changing the crosslinking density. However, the interdependent nature of the structural, physical and biological properties of photocrosslinkable hydrogels means that optimizing composition is typically a complicated process, involving sequential and/or iterative steps of physiochemical and biological characterization. The combinational nature of the variables indicates that an exhaustive analysis of all reasonable concentration ranges would be impractical. Herein, response surface methodology (RSM) was used to efficiently optimize the composition of a hybrid of gelatin‐methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) with respect to both mechanical and transport properties. RSM was employed to investigate the effect of GelMA, HAMA, and photoinitiator concentration on the shear modulus and diffusion coefficient of the hydrogel membrane. Two mathematical models were fitted to the experimental data and used to predict the optimum hydrogel composition. Finally, the optimal composition was tested and compared with the predicted values.

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          Response surface methodology (RSM) as a tool for optimization in analytical chemistry.

          A review about the application of response surface methodology (RSM) in the optimization of analytical methods is presented. The theoretical principles of RSM and steps for its application are described to introduce readers to this multivariate statistical technique. Symmetrical experimental designs (three-level factorial, Box-Behnken, central composite, and Doehlert designs) are compared in terms of characteristics and efficiency. Furthermore, recent references of their uses in analytical chemistry are presented. Multiple response optimization applying desirability functions in RSM and the use of artificial neural networks for modeling are also discussed.
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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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              Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks.

              Hyaluronic acid is a natural polysaccharide found abundantly throughout the body with many desirable properties for application as a biomaterial, including scaffolding for tissue engineering. In this work, hyaluronic acid with molecular weights ranging from 50 to 1100 kDa was modified with methacrylic anhydride and photopolymerized into networks with a wide range of physical properties. With macromer concentrations from 2 to 20 wt %, networks exhibited volumetric swelling ratios ranging from approximately 42 to 8, compressive moduli ranging from approximately 2 to over 100 kPa, and degradation times ranging from less than 1 day up to almost 38 days in the presence of 100 U/mL of hyaluronidase. When 3T3-fibroblasts were photoencapsulated in the hydrogels, cells remained viable with low macromer concentrations but decreased sequentially as the macromer concentration increased. Finally, auricular swine chondrocytes produced neocartilage when photoencapsulated in the hyaluronic acid networks. This work presents a next step toward the development of advanced in vivo curable biomaterials.
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                Author and article information

                Contributors
                gwallace@uow.edu.au
                Journal
                J Biomed Mater Res B Appl Biomater
                J Biomed Mater Res B Appl Biomater
                10.1002/(ISSN)1552-4981
                JBM
                Journal of Biomedical Materials Research. Part B, Applied Biomaterials
                John Wiley & Sons, Inc. (Hoboken, USA )
                1552-4973
                1552-4981
                21 October 2022
                March 2023
                : 111
                : 3 ( doiID: 10.1002/jbm.b.v111.3 )
                : 526-537
                Affiliations
                [ 1 ] ARC ITTC in Additive Biomanufacturing Queensland University of Technology Brisbane QLD Australia
                [ 2 ] ARC Centre of Excellence for Electromaterials Science (ACES), Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus University of Wollongong Wollongong New South Wales Australia
                [ 3 ] Discipline of Electrical and Biomedical Engineering, School of Engineering RMIT University Melbourne Victoria Australia
                [ 4 ] BioFab3D, Aikenhead Center for Medical Discovery, St Vincent's Hospital Melbourne Victoria Australia
                [ 5 ] Australian National Fabrication Facility‐Materials Node, Innovation Campus University of Wollongong Wollongong New South Wales Australia
                [ 6 ] Commonwealth Scientific Industrial Research Organization, Manufacturing Clayton Victoria Australia
                [ 7 ] Orthopaedic Department, St Vincent's Hospital Melbourne Victoria Australia
                [ 8 ] Department of Surgery University of Melbourne Melbourne Victoria Australia
                Author notes
                [*] [* ] Correspondence

                Gordon G. Wallace, ARC ITTC in Additive Biomanufacturing, Queensland University of Technology, Brisbane, QLD 4059, Australia.

                Email: gwallace@ 123456uow.edu.au

                Author information
                https://orcid.org/0000-0002-1690-9505
                Article
                JBMB35169
                10.1002/jbm.b.35169
                10092314
                36269163
                4031174e-57b5-48be-a0aa-44ddb4e705fa
                © 2022 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 08 May 2022
                : 12 October 2021
                : 11 May 2022
                Page count
                Figures: 8, Tables: 4, Pages: 12, Words: 6677
                Funding
                Funded by: Australian Research Council (ARC)
                Award ID: CE140100012
                Funded by: Australian National Fabrication Facility , doi 10.13039/100008015;
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                March 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:12.04.2023

                Biomaterials & Organic materials
                design of experiment,diffusion coefficient,gelatin methacryloyl (gelma),hyaluronic acid methacryloyl (hama),response surface methodology

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