Matthew Ho

Background: Osteoarthritis (OA) currently affects around 250 million people worldwide with an estimated cost of $303 billion a year, and its prevalence is only expected to increase by 50% in the next decade.¹ Osteoarthritis occurs when an initial chronic or acute injury damages a joint and elevates proinflammatory cytokines.⁵ These proinflammatory cytokines, such as IL6,8, and TNF-α, contribute to joint degradation by inhibiting matrix synthesis and stimulating matrix-degrading enzymes such as matrix metalloproteinases (MMPs).⁵ In response to this damage, chondrocytes in the cartilage produce more inflammatory cytokines in a destructive cycle that must be interrupted for healing and repair.⁴ This is made more difficult by the lack of vascularization and blood flow in these areas.³ Current non-invasive therapies for cartilage repair focus on symptom relief rather than repairing or preventing deterioration.⁵ Tissue engineering, such as 3D scaffolds, has recently emerged as a potential solution to these problems, offering customizable properties including material and structure.⁵

Objective: In this review, we explore how the structure, material, and the addition of anti-inflammatory substances of a 3D bio-printed scaffold affect the healing of knee OA.

Search Methods: An online search in the PubMed database was conducted from 2019-2024 using the following keywords: “scaffolding”, “osteoarthritis”, “silk fibroin”, “anti-inflammatory”, “cartilage”, and “bioactive materials”.

Results: In a study, a macro-porous hydrogel scaffold was created by cross-linking silk fibroin (SF) and gelatin (GT) through extrusion-based printing. The gelatin provided adjustable thermosensitivity and gel kinetics and the covalent crosslinking with silk fibroin provided final stabilization.² The addition of mesenchymal stem cells (MSC) using the cellular aggregate seeding method improved MSC retention and resulted in a higher collagen type II level, which has superior performance, than type I.² Another study experimented with the addition of tannic acid (TA), which is a natural antioxidant that can bind to IL-1β by blocking its interaction with IL-1R, and inhibits the corresponding proinflammatory signaling cascade. When added to the SF scaffold in a rat OA model, the coating effectively downregulates the expression of proinflammatory molecules such as IL-6, IL-8, and MMPs. Additionally, it inhibits cartilage degeneration and delays OA development.⁸

Conclusion: Studies found the crosslinking of silk fibroin and gelatin had excellent structural stability, suitable mechanical properties, and an adjustable degradation rate in hydrogel.² Additionally, another study showed that the addition of tannic acid effectively downregulated cytokines IL-6, IL-8, and MMPs. Thus, the use of 3d printed SF-GT scaffolds with tannic acid shows promise for patients who want to treat the underlying cause of OA with a less invasive treatment.^2,8

Works Cited:

1. Zhou Z, Cui J, Wu S, Geng Z, Su J. Silk fibroin-based biomaterials for cartilage/osteochondral repair. Theranostics. 2022;12(11):5103-5124. Published 2022 Jul 4. doi:10.7150/thno.74548
2. Li Q, Xu S, Feng Q, et al. 3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration. Bioact Mater. 2021;6(10):3396-3410. Published 2021 Mar 19. doi:10.1016/j.bioactmat.2021.03.013
3. Zhou J, Li Q, Tian Z, Yao Q, Zhang M. Recent advances in 3D bioprinted cartilage-mimicking constructs for applications in tissue engineering. Mater Today Bio. 2023;23:100870. Published 2023 Nov 17. doi:10.1016/j.mtbio.2023.100870
4.  Jang S, Lee K, Ju JH. Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee. Int J Mol Sci. 2021;22(5):2619. Published 2021 Mar 5. doi:10.3390/ijms22052619
5.  Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA. 2021;325(6):568-578. doi:10.1001/jama.2020.22171
6. Wu T, Chen Y, Liu W, et al. 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. doi:10.1016/j.msec.2020.110757
7. Hasturk O, Jordan KE, Choi J, Kaplan DL. Enzymatically crosslinked silk and silk-gelatin hydrogels with tunable gelation kinetics, mechanical properties and bioactivity for cell culture and encapsulation. Biomaterials. 2020;232:119720. doi:10.1016/j.biomaterials.2019.119720
8. Li Y, Chen M, Yan J, et al. Tannic acid/Sr2+-coated silk/graphene oxide-based meniscus scaffold with anti-inflammatory and anti-ROS functions for cartilage protection and delaying osteoarthritis. Acta Biomater. 2021;126:119-131. doi:10.1016/j.actbio.2021.02.046
9. Yeo J, Lee J, Yoon S, Kim WJ. Tannic acid-based nanogel as an efficient anti-inflammatory agent. Biomater Sci. 2020;8(4):1148-1159. doi:10.1039/c9bm01384a
10. Lee HR, Jeong YJ, Lee JW, et al. Tannic acid, an IL-1β-direct binding compound, ameliorates IL-1β-induced inflammation and cartilage degradation by hindering IL-1β-IL-1R1 interaction. PLoS One. 2023;18(4):e0281834. Published 2023 Apr 20. doi:10.1371/journal.pone.0281834
11. Liu J, Han X, Zhang T, Tian K, Li Z, Luo F. Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy. J Hematol Oncol. 2023;16(1):116. Published 2023 Nov 30. doi:10.1186/s13045-023-01512-7
12. Zhu S, Li Y, He Z, et al. Advanced injectable hydrogels for cartilage tissue engineering. Front Bioeng Biotechnol. 2022;10:954501. Published 2022 Sep 8. doi:10.3389/fbioe.2022.954501