Hydrogel-Based 3D Bioprinting Technology for Articular Cartilage Regenerative Engineering
Abstract
1. Introduction
2. Traditional Approaches for Articular Cartilage Repair or Regeneration
3. Tissue Engineering for Treatment of Cartilage Damages
4. Three-Dimensional Bioprinting Materials for Articular Cartilage Repair or Regeneration
4.1. Natural Hydrogels
4.1.1. Alginate
4.1.2. HA
4.1.3. Collagen
4.1.4. SF
4.2. Synthetic Hydrogels
4.2.1. PEG-Based Hydrogel
4.2.2. GelMA-Based Hydrogel
4.2.3. PLA- and PLA Copolymer-Based Hydrogel
4.2.4. PVA-Based Hydrogel
4.2.5. HAMA-Based Hydrogel
4.2.6. Methylcellulose-Based Hydrogel
4.2.7. Polyurethane-Based Hydrogel
5. Conclusions, Challenges and Prospects
Funding
Acknowledgments
Conflicts of Interest
References
- Giorgino, R.; Albano, D.; Fusco, S.; Peretti, G.M.; Mangiavini, L.; Messina, C. Knee Osteoarthritis: Epidemiology, Pathogenesis, and Mesenchymal Stem Cells: What Else Is New? An Update. Int. J. Mol. Sci. 2023, 24, 6405. [Google Scholar] [CrossRef] [PubMed]
- Sampath, S.J.P.; Venkatesan, V.; Ghosh, S.; Kotikalapudi, N. Obesity, Metabolic Syndrome, and Osteoarthritis—An Updated Review. Curr. Obes. Rep. 2023, 12, 308–331. [Google Scholar] [CrossRef] [PubMed]
- Richter, D.L.; Schenck, R.C., Jr.; Wascher, D.C.; Treme, G. Knee Articular Cartilage Repair and Restoration Techniques: A Review of the Literature. Sports Health 2016, 8, 153–160. [Google Scholar] [CrossRef] [PubMed]
- Makris, E.A.; Gomoll, A.H.; Malizos, K.N.; Hu, J.C.; Athanasiou, K.A. Repair and Tissue Engineering Techniques for Articular Cartilage. Nat. Rev. Rheumatol. 2015, 11, 21–34. [Google Scholar] [CrossRef] [PubMed]
- Bai, X.S.; Thomas, J.M.; Ha, A.S. Surgical Correction of Articular Damage in the Knee: Osteoarticular Transplantation to Joint Reconstruction. Semin. Musculoskelet. Radiol. 2017, 21, 147–164. [Google Scholar] [PubMed]
- Kwon, H.; Brown, W.E.; Lee, C.A.; Wang, D.; Paschos, N.; Hu, J.C.; Athanasiou, K.A. Surgical and Tissue Engineering Strategies for Articular Cartilage and Meniscus Repair. Nat. Rev. Rheumatol. 2019, 15, 550–570. [Google Scholar] [CrossRef] [PubMed]
- Kluyskens, L.; Debieux, P.; Wong, K.L.; Krych, A.J.; Saris, D.B.F. Biomaterials for Meniscus and Cartilage in Knee Surgery: State of the Art. J. ISAKOS 2022, 7, 67–77. [Google Scholar] [CrossRef] [PubMed]
- Ahmadian, E.; Eftekhari, A.; Janas, D.; Vahedi, P. Nanofiber Scaffolds Based on Extracellular Matrix for Articular Cartilage Engineering: A Perspective. Nanotheranostics 2023, 7, 61–69. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Tang, C.; Huang, J.; Gu, J.; Yin, J.; Xu, G.; Yan, S. Nanofiber Composite Microchannel-Containing Injectable Hydrogels for Cartilage Tissue Regeneration. Adv. Healthc. Mater. 2023, 12, e2302293. [Google Scholar] [CrossRef]
- Li, M.; Sun, D.; Zhang, J.; Wang, Y.; Wei, Q.; Wang, Y. Application and Development of 3D Bioprinting in Cartilage Tissue Engineering. Biomater. Sci. 2022, 10, 5430–5458. [Google Scholar] [CrossRef]
- Deus, I.A.; Santos, S.C.; Custódio, C.A.; Mano, J.F. Designing Highly Customizable Human Based Platforms for Cell Culture Using Proteins from the Amniotic Membrane. Biomater. Adv. 2022, 134, 112574. [Google Scholar] [CrossRef]
- Loukelis, K.; Helal, Z.A.; Mikos, A.G.; Chatzinikolaidou, M. Nanocomposite Bioprinting for Tissue Engineering Applications. Gels 2023, 9, 103. [Google Scholar] [CrossRef] [PubMed]
- Ruiz-Cantu, L.; Gleadall, A.; Faris, C.; Segal, J.; Shakesheff, K.; Yang, J. Multi-material 3D Bioprinting of Porous Constructs for Cartilage Regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2020, 109, 110578. [Google Scholar] [CrossRef] [PubMed]
- Amler, A.K.; Dinkelborg, P.H.; Schlauch, D.; Spinnen, J.; Stich, S.; Lauster, R.; Sittinger, M.; Nahles, S.; Heiland, M.; Kloke, L.; et al. Comparison of the Translational Potential of Human Mesenchymal Progenitor Cells from Different Bone Entities for Autologous 3D Bioprinted Bone Grafts. Int. J. Mol. Sci. 2021, 22, 796. [Google Scholar] [CrossRef] [PubMed]
- Thangadurai, M.; Srinivasan, S.S.; Sekar, M.P.; Sethuraman, S.; Sundaramurthi, D. Emerging Perspectives on 3D Printed Bioreactors for Clinical Translation of Engineered and Bioprinted Tissue Constructs. J. Mater. Chem. B 2024, 12, 350–381. [Google Scholar] [CrossRef]
- Li, Q.; Yu, H.; Zhao, F.; Cao, C.; Wu, T.; Fan, Y.; Ao, Y.; Hu, X. 3D Printing of Microenvironment-Specific Bioinspired and Exosome-Reinforced Hydrogel Scaffolds for Efficient Cartilage and Subchondral Bone Regeneration. Adv. Sci. 2023, 10, e2303650. [Google Scholar] [CrossRef]
- Hunziker, E.B.; Quinn, T.M.; Häuselmann, H.J. Quantitative Structural Organization of Normal Adult Human Articular Cartilage. Osteoarthr. Cartil. 2002, 10, 564–572. [Google Scholar] [CrossRef]
- Goyal, N.; Gupta, M. Computerized Morphometric Analysis of Human Femoral Articular Cartilage. ISRN Rheumatol. 2012, 2012, 360201. [Google Scholar] [CrossRef]
- Carballo, C.B.; Nakagawa, Y.; Sekiya, I.; Rodeo, S.A. Basic Science of Articular Cartilage. Clin. Sports Med. 2017, 36, 413–425. [Google Scholar] [CrossRef]
- Lepage, S.I.M.; Robson, N.; Gilmore, H.; Davis, O.; Hooper, A.; St John, S.; Kamesan, V.; Gelis, P.; Carvajal, D.; Hurtig, M.; et al. Beyond Cartilage Repair: The Role of the Osteochondral Unit in Joint Health and Disease. Tissue Eng. Part. B Rev. 2019, 25, 114–125. [Google Scholar] [CrossRef]
- Armiento, A.R.; Alini, M.; Stoddart, M.J. Articular Fibrocartilage—Why Does Hyaline Cartilage Fail to Repair? Adv. Drug Deliv. Rev. 2019, 146, 289–305. [Google Scholar] [CrossRef] [PubMed]
- Craddock, R.J.; Hodson, N.W.; Ozols, M.; Shearer, T.; Hoyland, J.A.; Sherratt, M.J. Extracellular Matrix Fragmentation in Young, Healthy Cartilaginous Tissues. Eur. Cell Mater. 2018, 35, 34–53. [Google Scholar] [CrossRef] [PubMed]
- Cutolo, M.; Berenbaum, F.; Hochberg, M.; Punzi, L.; Reginster, J.Y. Commentary on Recent Therapeutic Guidelines for Osteoarthritis. Semin. Arthritis Rheum. 2015, 44, 611–617. [Google Scholar] [CrossRef] [PubMed]
- Jang, S.; Lee, K.; Ju, J.H. Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee. Int. J. Mol. Sci. 2021, 22, 2619. [Google Scholar] [CrossRef] [PubMed]
- Kamaruzaman, H.; Kinghorn, P.; Oppong, R. Cost-Effectiveness of Surgical Interventions for the Management of Osteoarthritis: A Systematic Review of the Literature. BMC. Musculoskelet. Disord. 2017, 18, 183. [Google Scholar] [CrossRef] [PubMed]
- Murphy, M.; Barry, F. Cellular Chondroplasty: A New Technology for Joint Regeneration. J. Knee Surg. 2015, 28, 45–50. [Google Scholar] [CrossRef] [PubMed]
- Salzmann, G.M.; Ossendorff, R.; Gilat, R.; Cole, B.J. Autologous Minced Cartilage Implantation for Treatment of Chondral and Osteochondral Lesions in the Knee Joint: An Overview. Cartilage 2021, 13, 1124S–1136S. [Google Scholar] [CrossRef] [PubMed]
- Jayakumar, P.; Bozic, K.J. Advanced Decision-Making Using Patient-Reported Outcome Measures in Total Joint Replacement. J. Orthop. Res. 2020, 38, 1414–1422. [Google Scholar] [CrossRef]
- Fang, M.; Noiseux, N.; Linson, E.; Cram, P. The Effect of Advancing Age on Total Joint Replacement Outcomes. Geriatr. Orthop. Surg. Rehabil. 2015, 6, 173. [Google Scholar] [CrossRef]
- Dumenci, L.; Perera, R.A.; Keefe, F.J.; Ang, D.C.; Slover, J.; Jensen, M.P.; Riddle, D.L. Model-Based Pain and Function Outcome Trajectory Types for Patients Undergoing Knee Arthroplasty: A Secondary Analysis from a Randomized Clinical Trial. Osteoarthr. Cartil. 2019, 27, 878–884. [Google Scholar] [CrossRef]
- Teterycz, D.; Ferry, T.; Lew, D.; Stern, R.; Assal, M.; Hoffmeyer, P.; Bernard, L.; Uçkay, I. Outcome of Orthopedic Implant Infections Due to Different Staphylococci. Int. J. Infect. Dis. 2010, 14, e913–e918. [Google Scholar] [CrossRef]
- Gu, A.; Malahias, M.A.; Selemon, N.A.; Wei, C.; Gerhard, E.F.; Cohen, J.S.; Fassihi, S.C.; Stake, S.; Bernstein, S.L.; Chen, A.Z.; et al. Increased Severity of Anaemia Is Associated with 30-Day Complications Following Total Joint Replacement. Bone Jt. J. 2020, 102, 485–494. [Google Scholar] [CrossRef] [PubMed]
- Pastor, M.F.; Smith, T.; Wellmann, M. Options in Joint-preserving Surgical Treatment of Osteoarthritis. Orthopade 2018, 47, 377–382. [Google Scholar] [CrossRef]
- Mühlhofer, H.M.L.; Feihl, S.; Suren, C.; Banke, I.G.J.; Pohlig, F.; von Eisenhart-Rothe, R. Implant-associated Joint Infections. Orthopade 2020, 49, 277–286. [Google Scholar] [CrossRef] [PubMed]
- Mardones, R.; Jofre, C.M.; Minguell, J.J. Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration. Int. J. Stem Cells 2015, 8, 48–53. [Google Scholar] [CrossRef] [PubMed]
- Reina-Mahecha, A.; Beers, M.J.; van der Veen, H.C.; Zuhorn, I.S.; van Kooten, T.G.; Sharma, P.K. A Review of the Role of Bioreactors for iPSCs-Based Tissue Engineered Articular Cartilage. Tissue Eng. Regen. Med. 2023, 20, 1041–1052. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.S.; Kim, H.K.; Kim, D.W. Cartilage Tissue Engineering for Craniofacial Reconstruction. Arch. Plast. Surg. 2020, 47, 392–403. [Google Scholar] [CrossRef]
- Zopf, D.A.; Flanagan, C.L.; Mitsak, A.G.; Brennan, J.R.; Hollister, S.J. Pore Architecture Effects on Chondrogenic Potential of Patient-Specific 3-Dimensionally Printed Porous Tissue Bioscaffolds for Auricular Tissue Engineering. Int. J. Pediatr. Otorhinolaryngol. 2018, 114, 170–174. [Google Scholar] [CrossRef]
- Eftekhari, A.; Maleki Dizaj, S.; Sharifi, S.; Salatin, S.; Rahbar Saadat, Y.; Zununi Vahed, S.; Samiei, M.; Ardalan, M.; Rameshrad, M.; Ahmadian, E. The Use of Nanomaterials in Tissue Engineering for Cartilage Regeneration; Current Approaches and Future Perspectives. Int. J. Mol. Sci. 2020, 21, 536. [Google Scholar] [CrossRef]
- Nie, X.; Chuah, Y.J.; Zhu, W.; He, P.; Peck, Y.; Wang, D.A. Decellularized Tissue Engineered Hyaline Cartilage Graft for Articular Cartilage Repair. Biomaterials 2020, 235, 119821. [Google Scholar] [CrossRef]
- Baei, P.; Daemi, H.; Aramesh, F.; Baharvand, H.; Eslaminejad, M.B. Advances in Mechanically Robust and Biomimetic Polysaccharide-based Constructs for Cartilage Tissue Engineering. Carbohydr. Polym. 2023, 308, 120650. [Google Scholar] [CrossRef] [PubMed]
- Matai, I.; Kaur, G.; Seyedsalehi, A.; McClinton, A.; Laurencin, C.T. Progress in 3D Bioprinting Technology for Tissue/organ Regenerative Engineering. Biomaterials 2020, 226, 119536. [Google Scholar] [CrossRef]
- Zhao, T.; Liu, Y.; Wu, Y.; Zhao, M.; Zhao, Y. Controllable and Biocompatible 3D Bioprinting Technology for Microorganisms: Fundamental, Environmental Applications and Challenges. Biotechnol. Adv. 2023, 69, 108243. [Google Scholar] [CrossRef]
- Lepowsky, E.; Muradoglu, M.; Tasoglu, S. Towards Preserving Post-Printing Cell Viability and Improving the Resolution: Past, Present, and Future of 3D Bioprinting Theory. Bioprinting 2018, 11, e00034. [Google Scholar] [CrossRef]
- Gillispie, G.; Prim, P.; Copus, J.; Fisher, J.; Mikos, A.G.; Yoo, J.J.; Atala, A.; Lee, S.J. Assessment Methodologies for Extrusion-Based Bioink Printability. Biofabrication 2020, 12, 022003. [Google Scholar] [CrossRef]
- Malekpour, A.; Chen, X. Printability and Cell Viability in Extrusion-Based Bioprinting from Experimental, Computational, and Machine Learning Views. J. Funct. Biomater. 2022, 13, 40. [Google Scholar] [CrossRef]
- Daly, A.C.; Freeman, F.E.; Gonzalez-Fernandez, T.; Critchley, S.E.; Nulty, J.; Kelly, D.J. 3D Bioprinting for Cartilage and Osteochondral Tissue Engineering. Adv. Healthc. Mater. 2017, 6, 1700298. [Google Scholar] [CrossRef]
- Placone, J.K.; Engler, A.J. Recent Advances in Extrusion-based 3D Printing for Biomedical Applications. Adv. Healthc. Mater. 2018, 7, e1701161. [Google Scholar] [CrossRef]
- Murphy, S.V.; Atala, A. 3D Bioprinting of Tissues and Organs. Nat. Biotechnol. 2014, 32, 773–785. [Google Scholar] [CrossRef] [PubMed]
- Cui, X.; Boland, T.; DD’Lima, D.; Lotz, M.K. Thermal Inkjet Printing in Tissue Engineering and Regenerative Medicine. Recent Pat. Drug Deliv. Formul. 2012, 6, 149–155. [Google Scholar] [CrossRef] [PubMed]
- Saunders, R.E.; Gough, J.E.; Derby, B. Delivery of Human Fibroblast Cells by Piezoelectric Drop-on-Demand Inkjet Printing. Biomaterials 2008, 29, 193–203. [Google Scholar] [CrossRef] [PubMed]
- Saunders, R.E.; Derby, B. Inkjet Printing Biomaterials for Tissue Engineering: Bioprinting. Int. Mater. Rev. 2014, 59, 430–448. [Google Scholar] [CrossRef]
- Zhu, W.; Ma, X.; Gou, M.; Mei, D.; Zhang, K.; Chen, S. 3D Printing of Functional Biomaterials for Tissue Engineering. Curr. Opin. Biotechnol. 2016, 40, 103–112. [Google Scholar] [CrossRef] [PubMed]
- Jana, S.; Lerman, A. Bioprinting a Cardiac Valve. Biotechnol. Adv. 2015, 33, 1503–1521. [Google Scholar] [CrossRef] [PubMed]
- Barron, J.A.; Spargo, B.J.; Ringeisen, B.R. Biological Laser Printing of Three Dimensional Cellular Structures. Appl. Phys. A 2004, 79, 1027–1030. [Google Scholar] [CrossRef]
- Bishop, E.S.; Mostafa, S.; Pakvasa, M.; Luu, H.H.; Lee, M.J.; Wolf, J.M.; Ameer, G.A.; He, T.C.; Reid, R.R. 3-D Bioprinting Technologies in Tissue Engineering and Regenerative Medicine: Current and Future Trends. Genes Dis. 2017, 4, 185–195. [Google Scholar] [CrossRef] [PubMed]
- Melchels, F.P.W.; Feijen, J.; Grijpma, D.W. A Review on Stereolithography and Its Applications in Biomedical Engineering. Biomaterials 2010, 31, 6121–6130. [Google Scholar] [CrossRef] [PubMed]
- Grigoryan, B.; Sazer, D.W.; Avila, A.; Albritton, J.L.; Padhye, A.; Ta, A.H.; Greenfield, P.T.; Gibbons, D.L.; Miller, J.S. Development, Characterization, and Applications of Multi-Material Stereolithography Bioprinting. Sci. Rep. 2021, 11, 3171. [Google Scholar] [CrossRef] [PubMed]
- Mandrycky, C.; Wang, Z.; Kim, K.; Kim, D.-H. 3D Bioprinting for Engineering Complex Tissues. Biotechnol. Adv. 2016, 34, 422–434. [Google Scholar] [CrossRef]
- Heinrich, M.A.; Liu, W.; Jimenez, A.; Yang, J.; Akpek, A.; Liu, X.; Pi, Q.; Mu, X.; Hu, N.; Schiffelers, R.M.; et al. Bioprinting: 3D Bioprinting: From Benches to Translational Applications. Small 2019, 15, e1805510. [Google Scholar] [CrossRef]
- Fatimi, A. Exploring the Patent Landscape and Innovation of Hydrogel-based Bioinks Used for 3D Bioprinting. Recent Pat. Drug Deliv. Formul. 2022, 16, 145–163. [Google Scholar] [CrossRef]
- Michel, R.; Auzély-Velty, R. Hydrogel-Colloid Composite Bioinks for Targeted Tissue Printing. Biomacromolecules 2020, 21, 2949–2965. [Google Scholar] [CrossRef]
- Murab, S.; Gupta, A.; Włodarczyk-Biegun, M.K.; Kumar, A.; van Rijn, P.; Whitlock, P.; Han, S.S.; Agrawal, G. Alginate Based Hydrogel Inks for 3D Bioprinting of Engineered Orthopedic Tissues. Carbohydr. Polym. 2022, 296, 119964. [Google Scholar] [CrossRef]
- Hauptstein, J.; Böck, T.; Bartolf-Kopp, M.; Forster, L.; Stahlhut, P.; Nadernezhad, A.; Blahetek, G.; Zernecke-Madsen, A.; Detsch, R.; Jüngst, T.; et al. Hyaluronic Acid-Based Bioink Composition Enabling 3D Bioprinting and Improving Quality of Deposited Cartilaginous Extracellular Matrix. Adv. Healthc. Mater. 2020, 9, e2000737. [Google Scholar] [CrossRef]
- Yang, X.; Lu, Z.; Wu, H.; Li, W.; Zheng, L.; Zhao, J. Collagen-alginate as Bioink for Three-dimensional (3D) Cell Printing Based Cartilage Tissue Engineering. Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 83, 195–201. [Google Scholar] [CrossRef]
- Ni, T.; Liu, M.; Zhang, Y.; Cao, Y.; Pei, R. 3D Bioprinting of Bone Marrow Mesenchymal Stem Cell-Laden Silk Fibroin Double Network Scaffolds for Cartilage Tissue Repair. Bioconjug. Chem. 2020, 31, 1938–1947. [Google Scholar] [CrossRef]
- Wang, J.; Zhang, F.; Tsang, W.P.; Wan, C.; Wu, C. Fabrication of Injectable High Strength Hydrogel Based on 4-arm Star PEG For Cartilage Tissue Engineering. Biomaterials 2017, 120, 11–21. [Google Scholar] [CrossRef]
- Hölzl, K.; Fürsatz, M.; Göcerler, H.; Schädl, B.; Žigon-Branc, S.; Markovic, M.; Gahleitner, C.; Hoorick, J.V.; Van Vlierberghe, S.; Kleiner, A.; et al. Gelatin Methacryloyl as Environment for Chondrocytes and Cell Delivery to Superficial Cartilage Defects. J. Tissue Eng. Regen. Med. 2022, 16, 207–222. [Google Scholar] [CrossRef]
- Rosenzweig, D.H.; Carelli, E.; Steffen, T.; Jarzem, P.; Haglund, L. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration. Int. J. Mol. Sci. 2015, 16, 15118–15135. [Google Scholar] [CrossRef]
- Setayeshmehr, M.; Hafeez, S.; van Blitterswijk, C.; Moroni, L.; Mota, C.; Baker, M.B. Bioprinting Via a Dual-Gel Bioink Based on Poly(Vinyl Alcohol) and Solubilized Extracellular Matrix towards Cartilage Engineering. Int. J. Mol. Sci. 2021, 22, 3901. [Google Scholar] [CrossRef]
- Ma, K.; Zhao, T.; Yang, L.; Wang, P.; Jin, J.; Teng, H.; Xia, D.; Zhu, L.; Li, L.; Jiang, Q.; et al. Application of Robotic-assisted in Situ 3D Printing in Cartilage Regeneration with HAMA Hydrogel: An In Vivo Study. J. Adv. Res. 2020, 23, 123–132. [Google Scholar] [CrossRef] [PubMed]
- Tønnesen, H.H.; Karlsen, J. Alginate in Drug Delivery Systems. Drug Dev. Ind. Pharm. 2002, 28, 621–630. [Google Scholar] [CrossRef]
- Ruvinov, E.; Cohen, S. Alginate Biomaterial for the Treatment of Myocardial Infarction: Progress, Translational Strategies, and Clinical Outlook: From Ocean Algae to Patient Bedside. Adv. Drug Deliv. Rev. 2016, 96, 54–76. [Google Scholar] [CrossRef]
- Axpe, E.; Oyen, M.L. Applications of Alginate-Based Bioinks in 3D Bioprinting. Int. J. Mol. Sci. 2016, 17, 1976. [Google Scholar] [CrossRef]
- Hadley, D.J.; Silva, E.A. Thaw-Induced Gelation of Alginate Hydrogels for Versatile Delivery of Therapeutics. Ann. Biomed. Eng. 2019, 47, 1701–1710. [Google Scholar] [CrossRef]
- Catoira, M.C.; Fusaro, L.; Di Francesco, D.; Ramella, M.; Boccafoschi, F. Overview of Natural Hydrogels for Regenerative Medicine Applications. J. Mater. Sci. Mater. Med. 2019, 30, 115. [Google Scholar] [CrossRef] [PubMed]
- Öztürk, E.; Stauber, T.; Levinson, C.; Cavalli, E.; Arlov, Ø.; Zenobi-Wong, M. Tyrosinase-Crosslinked, Tissue Adhesive and Biomimetic Alginate Sulfate Hydrogels for Cartilage Repair. Biomed. Mater. 2020, 15, 045019. [Google Scholar] [CrossRef]
- Hontani, K.; Onodera, T.; Terashima, M.; Momma, D.; Matsuoka, M.; Baba, R.; Joutoku, Z.; Matsubara, S.; Homan, K.; Hishimura, R.; et al. Chondrogenic Differentiation of Mouse Induced Pluripotent Stem Cells Using the Three-Dimensional Culture with Ultra-Purified Alginate Gel. J. Biomed. Mater. Res. A 2019, 107, 1086–1093. [Google Scholar] [PubMed]
- Mahmoudi, Z.; Mohammadnejad, J.; Razavi Bazaz, S.; Abouei Mehrizi, A.; Saidijam, M.; Dinarvand, R.; Ebrahimi Warkiani, M.; Soleimani, M. Promoted Chondrogenesis of hMCSs with Controlled Release of TGF-Beta3 via Microfluidics Synthesized Alginate Nanogels. Carbohydr. Polym. 2020, 229, 115551. [Google Scholar] [CrossRef]
- Balakrishnan, B.; Joshi, N.; Jayakrishnan, A.; Banerjee, R. Self-Crosslinked Oxidized Alginate/Gelatin Hydrogel as Injectable, Adhesive Biomimetic Scaffolds for Cartilage Regeneration. Acta. Biomater. 2014, 10, 3650–3663. [Google Scholar] [CrossRef]
- Kundu, J.; Shim, J.H.; Jang, J.; Kim, S.W.; Cho, D.W. An Additive Manufacturing-Based PCL-Alginate-Chondrocyte Bioprinted Scaffold for Cartilage Tissue Engineering. J. Tissue Eng. Regen. Med. 2015, 9, 1286–1297. [Google Scholar] [CrossRef] [PubMed]
- Kosik-Kozioł, A.; Costantini, M.; Bolek, T.; Szöke, K.; Barbetta, A.; Brinchmann, J.; Święszkowski, W. PLA Short Sub-Micron Fiber Reinforcement of 3D Bioprinted Alginate Constructs for Cartilage Regeneration. Biofabrication 2017, 9, 044105. [Google Scholar] [CrossRef] [PubMed]
- Kilian, D.; Ahlfeld, T.; Akkineni, A.R.; Bernhardt, A.; Gelinsky, M.; Lode, A. 3D Bioprinting of Osteochondral Tissue Substitutes–in Vitro-Chondrogenesis in Multi-Layered Mineralized Constructs. Sci. Rep. 2020, 10, 8277. [Google Scholar] [CrossRef] [PubMed]
- Olate-Moya, F.; Arens, L.; Wilhelm, M.; Mateos-Timoneda, M.A.; Engel, E.; Palza, H. Chondroinductive Alginate-Based Hydrogels Having Graphene Oxide for 3D Printed Scaffold Fabrication. ACS Appl. Mater. Interfaces 2020, 12, 4343–4357. [Google Scholar] [CrossRef] [PubMed]
- Schwarz, S.; Kuth, S.; Distler, T.; Gögele, C.; Stölzel, K.; Detsch, R.; Boccaccini, A.R.; Schulze-Tanzil, G. 3D Printing and Characterization of Human Nasoseptal Chondrocytes Laden Dual Crosslinked Oxidized Alginate-gelatin Hydrogels for Cartilage Repair Approaches. Mater. Sci. Eng. C Mater. Biol. Appl. 2020, 116, 111189. [Google Scholar] [CrossRef] [PubMed]
- Yu, X.; Deng, Z.; Li, H.; Ma, Y.; Zheng, Q. In situ Fabrication of an Anisotropic Double-Layer Hydrogel as a Bio-Scaffold for Repairing Articular Cartilage and Subchondral Bone Injuries. RSC Adv. 2023, 13, 34958–34971. [Google Scholar] [CrossRef] [PubMed]
- Laporte, C.; Tubbs, E.; Pierron, M.; Gallego, A.; Moisan, A.; Lamarche, F.; Lozano, T.; Hernandez, A.; Cottet-Rousselle, C.; Gauchez, A.S.; et al. Improved Human Islets’ Viability and Functionality with Mesenchymal Stem Cells and Arg-gly-asp Tripeptides Supplementation of Alginate Micro-encapsulated Islets in Vitro. Biochem. Biophys. Res. Commun. 2020, 528, 650–657. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Yin, R.; Chen, X.; Wu, T.; Bu, Y.; Yan, H.; Lin, Q. Construction and Evaluation of Alginate Dialdehyde Grafted RGD Derivatives/Polyvinyl Alcohol/Cellulose Nanocrystals IPN Composite Hydrogels. Molecules 2023, 28, 6692. [Google Scholar] [CrossRef] [PubMed]
- Dumbleton, J.; Shamul, J.G.; Jiang, B.; Agarwal, P.; Huang, H.; Jia, X.; He, X. Oxidation and RGD Modification Affect the Early Neural Differentiation of Murine Embryonic Stem Cells Cultured in Core-Shell Alginate Hydrogel Microcapsules. Cells Tissues Organs. 2022, 211, 294–303. [Google Scholar] [CrossRef]
- Lertwimol, T.; Sonthithai, P.; Hankamolsiri, W.; Kaewkong, P.; Uppanan, P. Development of Chondrocyte-Laden Alginate Hydrogels with Modulated Microstructure and Properties for Cartilage Regeneration. Biotechnol. Prog. 2023, 39, e3322. [Google Scholar] [CrossRef]
- Morshedloo, F.; Khoshfetrat, A.B.; Kazemi, D.; Ahmadian, M. Gelatin Improves Peroxidase-Mediated Alginate Hydrogel Characteristics as a Potential Injectable Hydrogel for Soft Tissue Engineering Applications. J. Biomed. Mater. Res. B Appl. Biomater. 2020, 108, 2950–2960. [Google Scholar] [CrossRef] [PubMed]
- Haung, S.M.; Lin, Y.T.; Liu, S.M.; Chen, J.C.; Chen, W.C. In Vitro Evaluation of a Composite Gelatin-Hyaluronic Acid-Alginate Porous Scaffold with Different Pore Distributions for Cartilage Regeneration. Gels 2021, 7, 165. [Google Scholar] [CrossRef] [PubMed]
- Migliore, A.; Procopio, S. Effectiveness and Utility of Hyaluronic Acid in Osteoarthritis. Clin. Cases Miner. Bone Metab. 2015, 12, 31–33. [Google Scholar] [CrossRef]
- Antich, C.; de Vicente, J.; Jiménez, G.; Chocarro, C.; Carrillo, E.; Montañez, E.; Gálvez-Martín, P.; Marchal, J.A. Bio-inspired Hydrogel Composed of Hyaluronic Acid and Alginate as a Potential Bioink for 3D Bioprinting of Articular Cartilage Engineering Constructs. Acta. Biomater. 2020, 106, 114–123. [Google Scholar] [CrossRef]
- Chen, H.; Xue, H.; Zeng, H.; Dai, M.; Tang, C.; Liu, L. 3D Printed Scaffolds Based on Hyaluronic Acid Bioinks for Tissue Engineering: A Review. Biomater. Res. 2023, 27, 137. [Google Scholar] [CrossRef] [PubMed]
- Wan, T.; Fan, P.; Zhang, M.; Shi, K.; Chen, X.; Yang, H.; Liu, X.; Xu, W.; Zhou, Y. Multiple Crosslinking Hyaluronic Acid Hydrogels with Improved Strength and 3D Printability. ACS Appl. Bio. Mater. 2022, 5, 334–343. [Google Scholar] [CrossRef]
- Abatangelo, G.; Vindigni, V.; Avruscio, G.; Pandis, L.; Brun, P. Hyaluronic Acid: Redefining its Role. Cells 2020, 9, 1743. [Google Scholar] [CrossRef]
- Tsanaktsidou, E.; Kammona, O.; Kiparissides, C. On The Synthesis and Characterization of Biofunctional Hyaluronic Acid Based Injectable Hydrogels for The Repair of Cartilage Lesions. Eur. Polym. J. 2019, 114, 47–56. [Google Scholar] [CrossRef]
- Hong, B.M.; Kim, H.C.; Jeong, J.E.; Park, S.A.; Park, W.H. Visible-Light-Induced Hyaluronate Hydrogel for Soft tissue Fillers. Int. J. Biol. Macromol. 2020, 165, 2834–2844. [Google Scholar] [CrossRef]
- Wang, H.; Xu, Y.; Wang, P.; Ma, J.; Wang, P.; Han, X.; Fan, Y.; Bai, D.; Sun, Y.; Zhang, X. Cell-Mediated Injectable Blend Hydrogel-BCP Ceramic Scaffold for In Situ Condylar Osteochondral Repair. Acta Biomater. 2021, 123, 364–378. [Google Scholar] [CrossRef]
- Shokri, A.; Ramezani, K.; Jamalpour, M.R.; Mohammadi, C.; Vahdatinia, F.; Irani, A.D.; Sharifi, E.; Haddadi, R.; Jamshidi, S.; Amirabad, L.M. In Vivo Efficacy of 3D-Printed Elastin–Gelatin–Hyaluronic Acid Scaffolds for Regeneration of Nasal Septal Cartilage Defects. J. Biomed. Mater. Res. B Appl. Biomater. 2022, 110, 614–624. [Google Scholar] [CrossRef]
- Shi, W.; Fang, F.; Kong, Y.; Greer, S.E.; Kuss, M.; Liu, B.; Xue, W.; Jiang, X.; Lovell, P.; Mohs, A.M.; et al. Dynamic Hyaluronic Acid Hydrogel with Covalent Linked Gelatin as an Anti-oxidative Bioink for Cartilage Tissue Engineering. Biofabrication 2021, 14, 014107. [Google Scholar] [CrossRef]
- Zhu, D.; Wang, H.; Trinh, P.; Heilshorn, S.C.; Yang, F. Elastin-Like Protein-Hyaluronic Acid (ELP-HA) Hydrogels with Decoupled Mechanical and Biochemical Cues for Cartilage Regeneration. Biomaterials 2017, 127, 132–140. [Google Scholar] [CrossRef]
- Lin, H.; Beck, A.M.; Shimomura, K.; Sohn, J.; Fritch, M.R.; Deng, Y.; Kilroy, E.J.; Tang, Y.; Alexander, P.G.; Tuan, R.S. Optimization of Photocrosslinked Gelatin/Hyaluronic Acid Hybrid Scaffold for the Repair of Cartilage Defect. J. Tissue Eng. Regen. Med. 2019, 13, 1418–1429. [Google Scholar] [CrossRef]
- Titan, A.; Schär, M.; Hutchinson, I.; Demange, M.; Chen, T.; Rodeo, S. Growth Factor Delivery to a Cartilage-Cartilage Interface Using Platelet-Rich Concentrates on a Hyaluronic Acid Scaffold. Arthroscopy 2020, 36, 1431–1440. [Google Scholar] [CrossRef]
- Depalle, B.; Qin, Z.; Shefelbine, S.J.; Buehler, M.J. Influence of Cross-link Structure, Density and Mechanical Properties in the Mesoscale Deformation Mechanisms of Collagen Fibrils. J. Mech. Behav. Biomed. Mater. 2015, 52, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Marques, C.F.; Diogo, G.S.; Pina, S.; Oliveira, J.M.; Silva, T.H.; Reis, R.L. Collagen-based Bioinks for Hard Tissue Engineering Applications: A Comprehensive Review. J. Mater. Sci. Mater. Med. 2019, 30, 32. [Google Scholar] [CrossRef]
- Hesse, E.; Hefferan, T.E.; Tarara, J.E.; Haasper, C.; Meller, R.; Krettek, C.; Lu, L.; Yaszemski, M.J. Collagen Type I Hydrogel Allows Migration, Proliferation, and Osteogenic Differentiation of Rat Bone Marrow Stromal Cells. J. Biomed. Mater. Res. A 2010, 94, 442–449. [Google Scholar] [CrossRef] [PubMed]
- Rezvani Ghomi, E.; Nourbakhsh, N.; Akbari Kenari, M.; Zare, M.; Ramakrishna, S. Collagen-Based Biomaterials for Biomedical Applications. J. Biomed. Mater. Res. B Appl. Biomater. 2021, 109, 1986–1999. [Google Scholar] [CrossRef]
- Lee, J.C.; Lee, S.Y.; Min, H.J.; Han, S.A.; Jang, J.; Lee, S.; Seong, S.C.; Lee, M.C. Synovium-Derived Mesenchymal Stem Cells Encapsulated in a Novel Injectable Gel Can Repair Osteochondral Defects in a Rabbit Model. Tissue Eng. Part A 2012, 18, 2173–2186. [Google Scholar] [CrossRef] [PubMed]
- Mafi, P.; Hindocha, S.; Mafi, R.; Khan, W.S. Evaluation of Biological Protein-Based Collagen Scaffolds in Cartilage and Musculoskeletal Tissue Engineering—A Systematic Review of the Literature. Curr. Stem Cell Res. Ther. 2012, 7, 302–309. [Google Scholar] [CrossRef]
- Lu, Z.; Doulabi, B.Z.; Huang, C.; Bank, R.A.; Helder, M.N. Collagen Type II Enhances Chondrogenesis in Adipose Tissue–Derived Stem Cells by Affecting Cell Shape. Tissue Eng. Part A 2010, 16, 81–90. [Google Scholar] [CrossRef]
- Lu, Z.; Liu, S.; Le, Y.; Qin, Z.; He, M.; Xu, F.; Zhu, Y.; Zhao, J.; Mao, C.; Zheng, L. An Injectable Collagen-Genipin-Carbon Dot Hydrogel Combined with Photodynamic Therapy to Enhance Chondrogenesis. Biomaterials 2019, 218, 119190. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.; Yang, G.H.; Kim, M.; Lee, J.; Huh, J.; Kim, G. Fabrication of Micro/Nanoporous Collagen/dECM/Silk-fibroin Biocomposite Scaffolds Using a Low Temperature 3D Printing Process for Bone Tissue Regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 84, 140–147. [Google Scholar] [CrossRef]
- Shim, J.H.; Jang, K.M.; Hahn, S.K.; Park, J.Y.; Jung, H.; Oh, K.; Park, K.M.; Yeom, J.; Park, S.H.; Kim, S.W.; et al. Three-dimensional Bioprinting of Multilayered Constructs Containing Human Mesenchymal Stromal Cells for Osteochondral Tissue Regeneration in the Rabbit Knee Joint. Biofabrication 2016, 8, 014102. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Yue, H.; Huang, W.; Lin, X.; Xie, X.; He, Z.; He, X.; Liu, S.; Bai, L.; Lu, B.; et al. Cryogenic 3D Printing of Heterogeneous Scaffolds with Gradient Mechanical Strengths and Spatial Delivery of Osteogenic Peptide/TGF-β1 for Osteochondral Tissue Regeneration. Biofabrication 2020, 12, 025030. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Wang, Z.; Xu, Y.; Xia, J.; Xu, Z.; Zhu, S.; Jin, M. Preparation of Chitosan/Recombinant Human Collagen-Based Photo-Responsive Bioinks for 3D Bioprinting. Gels 2022, 8, 314. [Google Scholar] [CrossRef]
- Lan, X.; Ma, Z.; Dimitrov, A.; Kunze, M.; Mulet-Sierra, A.; Ansari, K.; Osswald, M.; Seikaly, H.; Boluk, Y.; Adesida, A.B. Double Crosslinked Hyaluronic Acid and Collagen as a Potential Bioink for Cartilage Tissue Engineering. Int. J. Biol. Macromol. 2024, 1, 132819. [Google Scholar] [CrossRef]
- Li, Y.Y.; Choy, T.H.; Ho, F.C.; Chan, P.B. Scaffold Composition Affects Cytoskeleton Organization, Cell-Matrix Interaction and the Cellular Fate of Human Mesenchymal Stem Cells Upon Chondrogenic Differentiation. Biomaterials 2015, 52, 208–220. [Google Scholar] [CrossRef]
- Buma, P.; Pieper, J.S.; van Tienen, T.; van Susante, J.L.; van der Kraan, P.M.; Veerkamp, J.H.; van den Berg, W.B.; Veth, R.P.; van Kuppevelt, T.H. Cross-linked Type Ⅰ and Type Ⅱ Collagenous Matrices for the Repair of Full-thickness Articular Cartilage Defects—A Study in Rabbits. Biomatrerials 2003, 24, 3255–3263. [Google Scholar] [CrossRef]
- Yoon, H.J.; Kim, S.B.; Somaiya, D.; Noh, M.J.; Choi, K.B.; Lim, C.L.; Lee, H.Y.; Lee, Y.J.; Yi, Y.; Lee, K.H. Type II Collagen and Glycosaminoglycan Expression Induction in Primary Human Chondrocyte by TGF-beta1. BMC. Musculoskelet. Disord. 2015, 16, 141. [Google Scholar] [CrossRef]
- Tiruvannamalai Annamalai, R.; Mertz, D.R.; Daley, E.L.; Stegemann, J.P. Collagen Type II Enhances Chondrogenic Differentiation in Agarose-based Modular Microtissues. Cytotherapy 2016, 18, 263–277. [Google Scholar] [CrossRef] [PubMed]
- Huang, W.; Ling, S.; Li, C.; Omenetto, F.G.; Kaplan, D.L. Silkworm Silk-Based Materials and Devices Generated Using Bio-nanotechnology. Chem. Soc. Rev. 2018, 47, 6486–6504. [Google Scholar] [CrossRef]
- Tong, X.; Pan, W.; Su, T.; Zhang, M.; Qi, X. Recent Advances in Natural Polymer-based Drug Delivery Systems. React. Funct. Polym. 2020, 148, 104501. [Google Scholar] [CrossRef]
- Nguyen, A.T.; Huang, Q.L.; Yang, Z.; Lin, N.; Xu, G.; Liu, X.Y. Crystal Networks in Silk Fibrous Materials: From Hierarchical Structure to Ultra Performance. Small 2015, 11, 1039–1054. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Xia, K.; Zhang, Y.; Kaplan, D.L. Silk-Based Advanced Materials for Soft Electronics. Acc. Chem. Res. 2019, 52, 2916–2927. [Google Scholar] [CrossRef]
- Melke, J.; Midha, S.; Ghosh, S.; Ito, K.; Hofmann, S. Silk Fibroin as Biomaterial for Bone Tissue Engineering. Acta Biomater. 2016, 31, 1–16. [Google Scholar] [CrossRef]
- Singh, Y.P.; Bandyopadhyay, A.; Mandal, B.B. 3D Bioprinting Using Cross-Linker-Free Silk-Gelatin Bioink for Cartilage Tissue Engineering. ACS Appl. Mater. Interfaces 2019, 11, 33684–33696. [Google Scholar] [CrossRef]
- Chawla, S.; Kumar, A.; Admane, P.; Bandyopadhyay, A.; Ghosh, S. Elucidating Role of Silk-Gelatin Bioink to Recapitulate Articular Cartilage Differentiation in 3D Bioprinted Constructs. Bioprinting 2017, 7, 1–13. [Google Scholar] [CrossRef]
- Rodriguez, M.J.; Brown, J.; Giordano, J.; Lin, S.J.; Omenetto, F.G.; Kaplan, D.L. Silk Based Bioinks for Soft Tissue Reconstruction Using 3-Dimensional (3D) Printing with In Vitro and in Vivo Assessments. Biomaterials 2017, 117, 105–115. [Google Scholar] [CrossRef]
- Geão, C.; Costa-Pinto, A.R.; Cunha-Reis, C.; Ribeiro, V.P.; Vieira, S.; Oliveira, J.M.; Reis, R.L.; Oliveira, A.L. Thermal Annealed Silk Fibroin Membranes for Periodontal Guided Tissue Regeneration. J. Mater. Sci. Mater. Med. 2019, 30, 27. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.; Zhou, L.; Li, Y.; Lou, X. Osteoblast-Derived Extracellular Matrix Coated PLLA/Silk Fibroin Composite Nanofibers Promote Osteogenic Differentiation of Bone Mesenchymal Stem Cells. J. Biomed. Mater. Res. A 2022, 110, 525–534. [Google Scholar] [CrossRef] [PubMed]
- Kulchar, R.J.; Denzer, B.R.; Chavre, B.M.; Takegami, M.; Patterson, J. A Review of the Use of Microparticles for Cartilage Tissue Engineering. Int. J. Mol. Sci. 2021, 22, 10292. [Google Scholar] [CrossRef] [PubMed]
- Wu, T.; Chen, Y.; Liu, W.; Tong, K.L.; Suen, C.-W.W.; Huang, S.; Hou, H.; She, G.; Zhang, H.; Zheng, X. Ginsenoside Rb1/TGF-β1 Loaded Biodegradable Silk Fibroin-Gelatin Porous Scaffolds for Inflammation Inhibition and Cartilage Regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2020, 111, 110757. [Google Scholar] [CrossRef] [PubMed]
- Wang, T.; Li, Y.; Liu, J.; Fang, Y.; Guo, W.; Liu, Y.; Li, X.; Li, G.; Wang, X.; Zheng, Z. Intraarticularly Injectable Silk Hydrogel Microspheres with Enhanced Mechanical and Structural Stability to Attenuate Osteoarthritis. Biomaterials 2022, 286, 121611. [Google Scholar] [CrossRef] [PubMed]
- Shi, W.; Sun, M.; Hu, X.; Ren, B.; Cheng, J.; Li, C.; Duan, X.; Fu, X.; Zhang, J.; Chen, H. Structurally and Functionally Optimized Silk-Fibroin–Gelatin Scaffold Using 3D Printing to Repair Cartilage Injury In Vitro and In Vivo. Adv. Mater. 2017, 29, 1701089. [Google Scholar] [CrossRef]
- Pan, Z.; Hou, M.; Zhang, Y.; Liu, Y.; Tian, X.; Hu, X.; Ge, X.; Zhao, Z.; Liu, T.; Xu, Y.; et al. Incorporation of Kartogenin and Silk Fibroin Scaffolds Promotes Rat Articular Regeneration through Enhancement of Antioxidant Functions. Regen. Biomater. 2023, 10, rbad074. [Google Scholar] [CrossRef] [PubMed]
- Chakraborty, J.; Fernández-Pérez, J.; Van Kampen, K.A.; Roy, S.; ten Brink, T.; Mota, C.; Ghosh, S.; Moroni, L. Development of a Biomimetic Arch-like 3D Bioprinted Construct for Cartilage Regeneration Using Gelatin Methacryloyl and Silk Fibroin-gelatin Bioinks. Biofabrication 2023, 15, 035009. [Google Scholar] [CrossRef] [PubMed]
- Wu, D.; Li, J.; Wang, C.; Su, Z.; Su, H.; Chen, Y.; Yu, B. Injectable Silk Fibroin Peptide Nanofiber Hydrogel Composite Scaffolds for Cartilage Regeneration. Mater. Today Bio. 2024, 25, 100962. [Google Scholar] [CrossRef] [PubMed]
- Yan, K.; Zhang, X.; Liu, Y.; Cheng, J.; Zhai, C.; Shen, K.; Liang, W.; Fan, W. 3D-bioprinted silk fibroin-hydroxypropyl cellulose methacrylate porous scaffold with optimized performance for repairing articular cartilage defects. Matr. Des. 2023, 225, 111531. [Google Scholar] [CrossRef]
- Zhou, J.; Wu, N.; Zeng, J.; Liang, Z.; Qi, Z.; Jiang, H.; Chen, H.; Liu, X. Chondrogenic Differentiation of Adipose-Derived Stromal Cells Induced by Decellularize Cartilage Matrix/Silk Fibroin Secondary Crosslinking Hydrogel Scaffolds with a Three-Dimensional Microstructure. Polymers 2023, 15, 1868. [Google Scholar] [CrossRef] [PubMed]
- Reddy, M.S.; Ponnamma, D.; Choudhary, R.; Sadasivuni, K.K. A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds. Polymers 2021, 13, 1105. [Google Scholar] [CrossRef] [PubMed]
- Hoffman, A.S. Hydrogels for Biomedical Applications. Adv. Drug Deliv. Rev. 2002, 54, 3–12. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Chen, G.; Xu, X.; Abdou, P.; Jiang, Q.; Shi, D.; Gu, Z. Advances of Injectable Hydrogel-Based Scaffolds for Cartilage Regeneration. Regen. Biomater. 2019, 6, 129–140. [Google Scholar] [CrossRef] [PubMed]
- Herzberger, J.; Niederer, K.; Pohlit, H.; Seiwert, J.; Worm, M.; Wurm, F.R.; Frey, H. Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation. Chem. Rev. 2015, 116, 2170–2243. [Google Scholar] [CrossRef] [PubMed]
- Choi, J.R.; Yong, K.W.; Choi, J.Y.; Cowie, A.C. Recent Advances in Photo-Crosslinkable Hydrogels for Biomedical Applications. Biotechniques 2019, 66, 40–53. [Google Scholar] [CrossRef]
- Ravi, S.; Chokkakula, L.P.; Giri, P.S.; Korra, G.; Dey, S.R.; Rath, S.N. 3D Bioprintable Hypoxia-Mimicking PEG-Based Nano Bioink for Cartilage Tissue Engineering. ACS Appl. Mater. Interfaces 2023, 15, 19921–19936. [Google Scholar] [CrossRef] [PubMed]
- Bandyopadhyay, A.; Mandal, B.B.; Bhardwaj, N. 3d Bioprinting of Photo-crosslinkable Silk Methacrylate (SilMA)-Polyethylene Glycol Diacrylate (PEGDA) Bioink for Cartilage Tissue Engineering. J. Biomed. Mater. Res. A 2021, 110, 884–898. [Google Scholar] [CrossRef]
- Fedorovich, N.E.; Oudshoorn, M.H.; van Geemen, D.; Hennink, W.E.; Alblas, J.; Dhert, W.J.A. The Effect of Photopolymerization on Stem Cells Embedded in Hydrogels. Biomaterials 2009, 30, 344–353. [Google Scholar] [CrossRef] [PubMed]
- Roberts, M.J.; Bentley, M.D.; Harris, J.M. Chemistry for Peptide and Protein PEGylation. Adv. Drug Deliv. Rev. 2002, 54, 459–476. [Google Scholar] [CrossRef]
- Kim, J.S.; Choi, J.; Ki, C.S.; Lee, K.H. 3D Silk Fiber Construct Embedded Dual-Layer PEG Hydrogel for Articular Cartilage Repair—In vitro Assessment. Front. Bioeng. Biotechnol. 2021, 9, 653509. [Google Scholar] [CrossRef] [PubMed]
- Wei, W.; Ma, Y.; Yao, X.; Zhou, W.; Wang, X.; Li, C.; Lin, J.; He, Q.; Leptihn, S.; Ouyang, H. Advanced Hydrogels for the Repair of Cartilage Defects and Regeneration. Bioact. Mater. 2021, 6, 998–1011. [Google Scholar] [CrossRef]
- Yang, M.; Deng, R.-H.; Yuan, F.-Z.; Zhang, J.-Y.; Zhang, Z.-N.; Chen, Y.-R.; Yu, J.-K. Immunomodulatory PEG-CRGD Hydrogels Promote Chondrogenic Differentiation of Pbmscs. Pharmaceutics 2022, 14, 2622. [Google Scholar] [CrossRef] [PubMed]
- Mad-Ali, S.; Benjakul, S.; Prodpran, T.; Maqsood, S. Characteristics and Gelling Properties of Gelatin from Goat Skin as Affected by Drying Methods. J. Food Sci. Technol. 2017, 54, 1646–1654. [Google Scholar] [CrossRef]
- Van Den Bulcke, A.I.; Bogdanov, B.; De Rooze, N.; Schacht, E.H.; Cornelissen, M.; Berghmans, H. Structural and Rheological Properties of Methacrylamide Modified Gelatin Hydrogels. Biomacromolecules 2000, 1, 31–38. [Google Scholar] [CrossRef] [PubMed]
- Yue, K.; Trujillo-de Santiago, G.; Alvarez, M.M.; Tamayol, A.; Annabi, N.; Khademhosseini, A. Synthesis, Properties, and Biomedical Applications of Gelatin Methacryloyl (GelMA) Hydrogels. Biomaterials 2015, 73, 254–271. [Google Scholar] [CrossRef] [PubMed]
- Young, A.T.; White, O.C.; Daniele, M.A. Rheological Properties of Coordinated Physical Gelation and Chemical Crosslinking in Gelatin Methacryloyl (GelMA) Hydrogels. Macromol. Biosci. 2020, 20, e2000183. [Google Scholar] [CrossRef] [PubMed]
- Miri, A.K.; Hosseinabadi, H.G.; Cecen, B.; Hassan, S.; Zhang, Y.S. Permeability Mapping of Gelatin Methacryloyl Hydrogels. Acta Biomater. 2018, 77, 38–47. [Google Scholar] [CrossRef] [PubMed]
- Paul, S.; Schrobback, K.; Tran, P.A.; Meinert, C.; Davern, J.W.; Weekes, A.; Klein, T.J. Photo-cross-linkable, Injectable, and Highly Adhesive GelMA-glycol Chitosan Hydrogels for Cartilage Repair. Adv. Healthc. Mater. 2023, 12, 2302078. [Google Scholar] [CrossRef]
- Liu, G.; Guo, Q.; Liu, C.; Bai, J.; Wang, H.; Li, J.; Liu, D.; Yu, Q.; Shi, J.; Liu, C.; et al. Cytomodulin-10 Modified GelMA Hydrogel with Kartogenin for in-Situ Osteochondral Regeneration. Acta Biomater. 2023, 169, 317–333. [Google Scholar] [CrossRef]
- Sun, T.; Feng, Z.; He, W.; Li, C.; Han, S.; Li, Z.; Guo, R. Novel 3D-printing Bilayer GelMA-based Hydrogel Containing BP, Beta-TCP and Exosomes for Cartilage-bone Integrated Repair. Biofabrication 2023, 16, 015008. [Google Scholar] [CrossRef]
- Yin, P.; Su, W.; Li, T.; Wang, L.; Pan, J.; Wu, X.; Shao, Y.; Chen, H.; Lin, L.; Yang, Y.; et al. A Modular Hydrogel Bioink Containing Microsphere-Embedded Chondrocytes for 3D-Printed Multiscale Composite Scaffolds for Cartilage Repair. iScience 2023, 26, 107349. [Google Scholar] [CrossRef] [PubMed]
- Gandini, A.; Lacerda, T.M. Monomers and Macromolecular Materials from Renewable Resources: State of the Art and Perspectives. Molecules 2021, 27, 159. [Google Scholar] [CrossRef] [PubMed]
- Li, G.; Zhao, M.; Xu, F.; Yang, B.; Li, X.; Meng, X.; Teng, L.; Sun, F.; Li, Y. Synthesis and Biological Application of Polylactic Acid. Molecules 2020, 25, 5023. [Google Scholar] [CrossRef] [PubMed]
- Farah, S.; Anderson, D.G.; Langer, R. Physical and Mechanical Properties of PLA, and Their Functions in Widespread Applications—A Comprehensive Review. Adv. Drug Deliv. Rev. 2016, 107, 367–392. [Google Scholar] [CrossRef]
- Oh, J.K. Polylactide (PLA)-Based Amphiphilic Block Copolymers: Synthesis, Self-Assembly, and Biomedical Applications. Soft Matter. 2011, 7, 5096. [Google Scholar] [CrossRef]
- Zeng, Z. Recent Advances in PEG-PLA Block Copolymer Nanoparticles. Int. J. Nanomed. 2010, 5, 1057–1065. [Google Scholar] [CrossRef] [PubMed]
- Tamai, N.; Myoui, A.; Hirao, M.; Kaito, T.; Ochi, T.; Tanaka, J.; Takaoka, K.; Yoshikawa, H. A New Biotechnology for Articular Cartilage Repair: Subchondral Implantation of a Composite of Interconnected Porous Hydroxyapatite, Synthetic Polymer (PLA-PEG), and Bone Morphogenetic Protein-2 (Rhbmp-2). Osteoarthr. Cartil. 2005, 13, 405–417. [Google Scholar] [CrossRef] [PubMed]
- Rahmani, F.; Atabaki, R.; Behrouzi, S.; Mohamadpour, F.; Kamali, H. The Recent Advancement in the PLGA-Based Thermo-Sensitive Hydrogel for Smart Drug Delivery. Int. J. Pharm. 2023, 631, 122484. [Google Scholar] [CrossRef]
- Li, S.; Niu, D.; Shi, T.; Yun, W.; Yan, S.; Xu, G.; Yin, J. Injectable, in Situ Self-Cross-Linking, Self-Healing Poly(l-Glutamic Acid)/Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering. ACS Biomater. Sci. Eng. 2023, 9, 2625–2635. [Google Scholar] [CrossRef]
- Xu, S.; Zhao, S.; Jian, Y.; Xu, Y.; Liu, W.; Shao, X.; Fan, J.; Wang, Y. Effect of Xanthohumol-Loaded Anti-Inflammatory Scaffolds on Cartilage Regeneration in Goats. Chin. J. Reparative Reconstr. Surg. 2022, 36, 1296–1304. [Google Scholar]
- Hedayati, H.R.; Khorasani, M.; Ahmadi, M.; Ballard, N. Preparation of Well-Defined Poly(Vinyl Alcohol) by Hydrolysis of Poly(Vinyl Acetate) Synthesized by Raft Suspension Polymerization. Polymer 2022, 246, 124674. [Google Scholar] [CrossRef]
- Chua, C.K.; Leong, K.F.; Tan, K.H.; Wiria, F.E.; Cheah, C.M. Development of Tissue Scaffolds Using Selective Laser Sintering of Polyvinyl Alcohol/Hydroxyapatite Biocomposite for Craniofacial and Joint Defects. J. Mater. Sci. Mater. Med. 2004, 15, 1113–1121. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Song, J.; Wang, S.; Liu, W. PVA-based Hydrogels: Promising Candidates for Articular Cartilage Repair. Macromol. Biosci. 2021, 21, e2100147. [Google Scholar] [CrossRef]
- Teodorescu, M.; Bercea, M.; Morariu, S. Biomaterials of PVA and PVP in Medical and Pharmaceutical Applications: Perspectives and Challenges. Biotechnol. Adv. 2019, 37, 109–131. [Google Scholar] [CrossRef] [PubMed]
- Zhu, C.; Huang, C.; Zhang, W.; Ding, X.; Yang, Y. Biodegradable-Glass-Fiber Reinforced Hydrogel Composite with Enhanced Mechanical Performance and Cell Proliferation for Potential Cartilage Repair. Int. J. Mol. Sci. 2022, 23, 8717. [Google Scholar] [CrossRef] [PubMed]
- Yao, H.; Kang, J.; Li, W.; Liu, J.; Xie, R.; Wang, Y.; Liu, S.; Wang, D.-A.; Ren, L. Novel β-TCP/PVA Bilayered Hydrogels with Considerable Physical and Bio-Functional Properties for Osteochondral Repair. Biomed. Mater. 2017, 13, 015012. [Google Scholar] [CrossRef] [PubMed]
- Bolandi, B.; Imani, R.; Bonakdar, S.; Fakhrzadeh, H. Chondrogenic Stimulation in Mesenchymal Stem Cells Using Scaffold-based Sustained Release of Platelet-rich Plasma. J. Appl. Polym. Sci. 2021, 138, e50075. [Google Scholar] [CrossRef]
- Mallakpour, S.; Tabesh, F.; Hussain, C.M. A New Trend of Using Poly (Vinyl Alcohol) in 3D and 4D Printing Technologies: Process and Applications. Adv. Colloid Interface Sci. 2022, 301, 102605. [Google Scholar] [CrossRef] [PubMed]
- Kumar, A.; Han, S.S. PVA-Based Hydrogels for Tissue Engineering: A Review. Int. J. Polym. Mater. Polym. Biomater. 2016, 66, 159–182. [Google Scholar] [CrossRef]
- Sionkowska, A.; Gadomska, M.; Musiał, K.; Piątek, J. Hyaluronic Acid as a Component of Natural Polymer Blends for Biomedical Applications: A Review. Molecules 2020, 25, 4035. [Google Scholar] [CrossRef] [PubMed]
- Tamer, T.M. Hyaluronan and Synovial Joint: Function, Distribution and Healing. Interdiscip. Toxicol. 2013, 6, 111–125. [Google Scholar] [CrossRef] [PubMed]
- Quintana, L.; zur Nieden, N.I.; Semino, C.E. Morphogenetic and Regulatory Mechanisms during Developmental Chondrogenesis: New Paradigms for Cartilage Tissue Engineering. Tissue Eng. Part B Rev. 2009, 15, 29–41. [Google Scholar] [CrossRef]
- Ito, T.; Williams, J.D.; Fraser, D.J.; Phillips, A.O. Hyaluronan Regulates Transforming Growth Factor-Β1 Receptor Compartmentalization. J. Biol. Chem. 2004, 279, 25326–25332. [Google Scholar] [CrossRef] [PubMed]
- Peterson, R.S.; Andhare, R.A.; Rousche, K.T.; Knudson, W.; Wang, W.; Grossfield, J.B.; Thomas, R.O.; Hollingsworth, R.E.; Knudson, C.B. CD44 Modulates SMAD1 Activation in the BMP-7 Signaling Pathway. J. Cell Biol. 2004, 166, 1081–1091. [Google Scholar] [CrossRef] [PubMed]
- Wang, M.; Deng, Z.; Guo, Y.; Xu, P. Designing Functional Hyaluronic Acid-Based Hydrogels for Cartilage Tissue Engineering. Mater. Today Bio 2022, 17, 100495. [Google Scholar] [CrossRef] [PubMed]
- Masters, K.S.; Shah, D.N.; Leinwand, L.A.; Anseth, K.S. Crosslinked Hyaluronan Scaffolds as a Biologically Active Carrier for Valvular Interstitial Cells. Biomaterials 2005, 26, 2517–2525. [Google Scholar] [CrossRef] [PubMed]
- Bencherif, S.A.; Srinivasan, A.; Horkay, F.; Hollinger, J.O.; Matyjaszewski, K.; Washburn, N.R. Influence of the Degree of Methacrylation on Hyaluronic Acid Hydrogels Properties. Biomaterials 2008, 29, 1739–1749. [Google Scholar] [CrossRef] [PubMed]
- Lam, T.; Dehne, T.; Krüger, J.P.; Hondke, S.; Endres, M.; Thomas, A.; Lauster, R.; Sittinger, M.; Kloke, L. Photopolymerizable Gelatin and Hyaluronic Acid for Stereolithographic 3D Bioprinting of Tissue-engineered Cartilage. J. Biomed. Mater. Res. B Appl. Biomater. 2019, 107, 2649–2657. [Google Scholar] [CrossRef]
- Martyniak, K.; Lokshina, A.; Cruz, M.A.; Karimzadeh, M.; Kean, T. Biomaterial Composition and Stiffness as Decisive Properties of 3D Bioprinted Constructs for Type II Collagen Stimulation. Acta Biomater. 2022, 152, 221–234. [Google Scholar] [CrossRef]
- Kesti, M.; Müller, M.; Becher, J.; Schnabelrauch, M.; D’Este, M.; Eglin, D.; Zenobi-Wong, M. A Versatile Bioink for Three-dimensional Printing of Cellular Scaffolds Based on Thermally and Photo-triggered Tandem Gelation. Acta Biomater. 2015, 11, 162–172. [Google Scholar] [CrossRef]
- Poldervaart, M.T.; Goversen, B.; de Ruijter, M.; Abbadessa, A.; Melchels, F.P.; Öner, F.C.; Dhert, W.J.; Vermonden, T.; Alblas, J. 3D Bioprinting of Methacrylated Hyaluronic Acid (MeHA) Hydrogel with Intrinsic Osteogenicity. PLoS ONE 2017, 12, e0177628. [Google Scholar] [CrossRef] [PubMed]
- Mallakpour, S.; Tukhani, M.; Hussain, C.M. Recent Advancements in 3D Bioprinting Technology of Carboxymethyl Cellulose-Based Hydrogels: Utilization in Tissue Engineering. Adv. Colloid Interface Sci. 2021, 292, 102415. [Google Scholar] [CrossRef] [PubMed]
- Bonetti, L.; De Nardo, L.; Farè, S. Crosslinking Strategies in Modulating Methylcellulose Hydrogel Properties. Soft Matter. 2023, 19, 7869–7884. [Google Scholar] [CrossRef] [PubMed]
- Takahashi, M.; Shimazaki, M.; Yamamoto, J. Thermoreversible Gelation and Phase Separation in Aqueous Methyl Cellulose Solutions. J. Polym. Sci. B Polym. Phys. 2000, 39, 91–100. [Google Scholar] [CrossRef]
- Haque, A.; Morris, E.R. Thermogelation of Methylcellulose. Part I: Molecular Structures and Processes. Carbohydr. Polym. 1993, 22, 161–173. [Google Scholar] [CrossRef]
- Roushangar Zineh, B.; Shabgard, M.R.; Roshangar, L. Mechanical and Biological Performance of Printed Alginate/Methylcellulose/Halloysite nanotube/Polyvinylidene Fluoride Bio-Scaffolds. Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 92, 779–789. [Google Scholar] [CrossRef] [PubMed]
- Hu, M.; Yang, J.; Xu, J. Structural and Biological Investigation of Chitosan/Hyaluronic Acid with Silanized-Hydroxypropyl Methylcellulose as an Injectable Reinforced Interpenetrating Network Hydrogel for Cartilage Tissue Engineering. Drug Deliv. 2021, 28, 607–619. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.; Lin, S.; Yan, Y.; You, X.; Ye, H. Enhanced Efficacy of Transforming Growth Factor-beta1 Loaded an Injectable Cross-linked Thiolated Chitosan and Carboxymethyl Cellulose-based Hydrogels for Cartilage Tissue Engineering. J. Biomater. Sci. Polym. Ed. 2021, 32, 2402–2422. [Google Scholar] [CrossRef]
- Cochis, A.; Grad, S.; Stoddart, M.J.; Farè, S.; Altomare, L.; Azzimonti, B.; Alini, M.; Rimondini, L. Bioreactor Mechanically Guided 3D Mesenchymal Stem Cell Chondrogenesis Using a Biocompatible Novel Thermo-Reversible Methylcellulose-Based Hydrogel. Sci. Rep. 2017, 7, 45018. [Google Scholar] [CrossRef]
- Hodder, E.; Duin, S.; Kilian, D.; Ahlfeld, T.; Seidel, J.; Nachtigall, C.; Bush, P.; Covill, D.; Gelinsky, M.; Lode, A. Investigating the Effect of Sterilisation Methods on the Physical Properties and Cytocompatibility of Methyl Cellulose Used in Combination with Alginate for 3D-Bioplotting of Chondrocytes. J. Mater. Sci. Mater. Med. 2019, 30, 10. [Google Scholar] [CrossRef] [PubMed]
- Ngadimin, K.D.; Stokes, A.; Gentile, P.; Ferreira, A.M. Biomimetic Hydrogels Designed for Cartilage Tissue Engineering. Biomater. Sci. 2021, 9, 4246–4259. [Google Scholar] [CrossRef] [PubMed]
- Janik, H.; Marzec, M. A Review: Fabrication of Porous Polyurethane Scaffolds. Mater. Sci. Eng. C Mater. Biol. Appl. 2015, 48, 586–591. [Google Scholar] [CrossRef] [PubMed]
- Versteegen, R.M.; Sijbesma, R.P.; Meijer, E.W. [N]-Polyurethanes: Synthesis and Characterization. Angew. Chem. Int. Ed. Engl. 1999, 38, 2917–2919. [Google Scholar] [CrossRef]
- Joseph, J.; Patel, R.; Wenham, A.; Smith, J. Biomedical Applications of Polyurethane Materials and Coatings. Trans. IMF 2018, 96, 121–129. [Google Scholar] [CrossRef]
- Thomas, S.; Datta, J.; Haponiuk, J.; Reghunadhan, A. Polyurethane Polymers: Blends and Interpenetrating Polymer Networks; Elsevier Ltd.: Amsterdam, The Netherlands, 2017. [Google Scholar]
- Cooper, S.L.; Guan, J.; Abraham, G.A. Advances in Polyurethane Biomaterials; Woodhead Publishing Ltd.: Cambridge, UK, 2016. [Google Scholar]
- Naureen, B.; Haseeb, A.S.M.A.; Basirun, W.J.; Muhamad, F. Recent Advances in Tissue Engineering Scaffold Based on Polyurethane and Modified Polyurethane. Mater. Sci. Eng. C Mater. Biol. Appl. 2021, 118, 111228. [Google Scholar] [CrossRef]
- Hung, K.C.; Tseng, C.S.; Dai, L.G.; Hsu, S. Water-Based Polyurethane 3D Printed Scaffolds with Controlled Release Function for Customized Cartilage Tissue Engineering. Biomaterials 2016, 83, 156–168. [Google Scholar] [CrossRef]
- Shie, M.Y.; Chang, W.C.; Wei, L.J.; Huang, Y.H.; Chen, C.H.; Shih, C.T.; Chen, Y.W.; Shen, Y.F. 3D Printing of Cytocompatible Water-Based Light-Cured Polyurethane with Hyaluronic Acid for Cartilage Tissue Engineering Applications. Materials 2017, 10, 136. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.W.; Shie, M.Y.; Chang, W.C.; Shen, Y.F. Approximate Optimization Study of Light Curing Waterborne Polyurethane Materials for the Construction of 3D Printed Cytocompatible Cartilage Scaffolds. Materials 2021, 14, 6804. [Google Scholar] [CrossRef]
- Grad, S.; Kupcsik, L.; Gorna, K.; Gogolewski, S.; Alini, M. The Use of Biodegradable Polyurethane Scaffolds for Cartilage Tissue Engineering: Potential and Limitations. Biomaterials 2003, 24, 5163–5171. [Google Scholar] [CrossRef]
Name | Chemical | Advantages | Limitations | References |
---|---|---|---|---|
Alginate |
|
| [72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92] | |
Hyaluronic acid (HA) |
|
| [93,94,95,96,97,98,99,100,101,102,103,104,105] | |
Collagen (COL) |
|
| [106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122] | |
Silk fibroin (SF) |
|
| [123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141] |
Name | Chemical | Advantages | Limitations | References |
---|---|---|---|---|
Polyethylene glycol (PEG) |
|
| [144,145,146,147,148,149,150,151,152,153] | |
Gelatin methacryloyl (GelMA) |
|
| [154,155,156,157,158,159,160,161,162] | |
Polylactic acid (PLA) |
|
| [163,164,165,166,167,168,169,170,171] | |
Polyvinyl alcohol (PVA) |
|
| [172,173,174,175,176,177,178,179,180] | |
Hyaluronic acid methacrylate (HAMA) |
|
| [181,182,183,184,185,186,187,188,189,190,191,192] | |
Methylcellulose (MC) |
|
| [193,194,195,196,197,198,199,200,201] | |
Polyurethane (PU) |
|
| [202,203,204,205,206,207,208,209,210,211,212] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhang, H.; Zhou, Z.; Zhang, F.; Wan, C. Hydrogel-Based 3D Bioprinting Technology for Articular Cartilage Regenerative Engineering. Gels 2024, 10, 430. https://doi.org/10.3390/gels10070430
Zhang H, Zhou Z, Zhang F, Wan C. Hydrogel-Based 3D Bioprinting Technology for Articular Cartilage Regenerative Engineering. Gels. 2024; 10(7):430. https://doi.org/10.3390/gels10070430
Chicago/Turabian StyleZhang, Hongji, Zheyuan Zhou, Fengjie Zhang, and Chao Wan. 2024. "Hydrogel-Based 3D Bioprinting Technology for Articular Cartilage Regenerative Engineering" Gels 10, no. 7: 430. https://doi.org/10.3390/gels10070430
APA StyleZhang, H., Zhou, Z., Zhang, F., & Wan, C. (2024). Hydrogel-Based 3D Bioprinting Technology for Articular Cartilage Regenerative Engineering. Gels, 10(7), 430. https://doi.org/10.3390/gels10070430