Written by Wonjin Ko '25
Edited by David Han '24
Around 867 million people around the world suffer from osteoarthritis, a degenerative medical condition caused by the erosion of cartilage in the joints [2]. This degradation occurs primarily in the knee, hips, and hands, and is more prevalent in older adults. In other words, one in every six adults experience joint pain caused by the breakdown of cartilage. This chronic pain only worsens over time, leading to even more severe pain, joint stiffness, and inflexibility.
Although there are many ways to alleviate the pain caused by osteoarthritis, no cure currently exists. Current treatments for osteoarthritis include medication, physical therapy, lifestyle changes, and surgery. These treatments, especially surgery, are invasive and can cause dramatic changes in one’s life. Even more, these treatments do not actually treat the disease, merely reducing pain and delaying the need for total joint replacement.
Many efforts have been made to restore cartilage in the joints, which could potentially cure osteoarthritis, and many other cartilage disorders. Some of these strategies include direct stimulation of the bone marrow (microfracture), growing cartilage cells in-vitro (autologous cartilage cell implantation), and grafting (osteochondral transplantation). However, such methods are typically unsuccessful, with a 25-50% failure rate and reduced efficiency in patients 40+ years, and require rehabilitation periods of one year or more. Other potential solutions being explored include more traditional orthopedic procedures, such as the implantation of metal caps onto the joint surface (joint resurfacing). Nevertheless, these methods are often more harmful in the long run, as it can lead to further joint damage caused by stiffness and excessive stress on the bone.
Hydrogels have been previously explored as an osteoarthritic treatment and have demonstrated hydrophilic properties and low permeability, making it an ideal substitute for cartilage in the body (which is immersed in body fluid). However, hydrogels had lacked the strength and durability to endure the amount of stress the joints undergo even doing basic movements, such as walking. Considering these drawbacks, researchers at Duke University have synthesized a promising hydrogel-based cartilage that mimics and even exceeds the strength of natural cartilage. This artificial cartilage has the potential to replicate the mechanical properties of natural cartilage, providing a cost-effective method of treatment.
What differentiates this new hydrogel from others is its particular composition, which allows for significant malleability and durability. In normal articular cartilage, water composes 60-85%, collagen fibers compose 15-22%, and negatively charged aggrecan composes 4-7% of the biological structure. The collagen fiber gives cartilage its durability under tension, while aggrecan contributes load-bearing properties. To mimic the structure of articular cartilage, the hydrogel is composed of three distinct polymers that each provide a unique function to the gel.
The artificial cartilage utilizes three distinct polymers, bacterial cellulose, polyvinyl alcohol, and PAMPS, to mimic the properties demonstrated by natural cartilage. Bacterial cellulose (BC) is a non-decomposable, biodegradable polymer that acts similar to the type II collagen present in cartilage, providing structural integrity to the hydrogel as it is stretched. Polyvinyl alcohol (PVA) gives the gel its elastic property, helping it maintain its original shape while also acting as an energy dissipator. Both BC and PVA electrostatically repel one another when compressed (i.e bending of a joint), which allows for the synthetic cartilage to maintain its structure. The third polymer, poly-2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt (PAMPS), mimics the negatively charged aggregate and is responsible for flexibility and increased strength, which helps the hydrogel endure strain without breaking. The interaction between these repeating polymer chains create the BC–PVA–PAMPS hydrogel, a jelly-like material composed of 60% water.
Another unique aspect of the new artificial cartilage is its strengthening process. Freeze-drying is a method used by many scientists to increase the strength of hydrogels. Freeze-drying a hydrogel stimulates crystallization, producing stable hydrogels with increased cross-linkage, which helps bind the polymer chains. The researchers at Duke discovered that annealing the BC–PVA–PAMPS hydrogel (heating it) yielded more crystallization than freeze drying it, further strengthening the polymer network.
Upon synthesizing the BC–PVA–PAMPS hydrogel, scientists at Duke have tested its ability to mimic the properties of cartilage. In theory, a potential replacement for cartilage should have similar or greater strength, elasticity, and durability. Stress-distribution and biocompatibility of the material into the body were also important factors. The hydrogel demonstrated a stress coefficient of 0.06, half of that of cartilage, a fatigue strength at 100,000 cycles, equivalent to that of cartilage, and was around 4 times more resistant to strain. Overall, the hydrogel matches and exceeds the properties of normal cartilage, making it a hopeful candidate for cartilage repair.
References
[1] Yang F, Zhao J, Koshut WJ, Watt J, Riboh JC, Gall K, et al. A Synthetic Hydrogel Composite with the Mechanical Behavior and Durability of Cartilage. Advanced Functional Materials. 2020;30(36):2003451.
[2] Wei W, Ma Y, Yao X, Zhou W, Wang X, Li C, et al. Advanced hydrogels for the repair of cartilage defects and regeneration. Bioact Mater. 2020 Oct 10;6(4):998–1011.
[3] Söntjens SHM, Nettles DL, Carnahan MA, Setton LA, Grinstaff MW. Biodendrimer-Based Hydrogel Scaffolds for Cartilage Tissue Repair. Biomacromolecules. 2006 Jan 1;7(1):310–6.
[4] Liao IC, Moutos FT, Estes BT, Zhao X, Guilak F. Composite Three-Dimensional Woven Scaffolds with Interpenetrating Network Hydrogels to Create Functional Synthetic Articular Cartilage. Advanced Functional Materials. 2013;23(47):5833–9.
[5] Zhao J, Kirillova A, Kelly CN, Xu H, Koshut WJ, Yang F, et al. High-Strength Hydrogel Attachment through Nanofibrous Reinforcement. Adv Healthc Mater. 2021 Feb;10(4):e2001119.
[6] Stiff, Achy Knees? Lab-Made Cartilage Gel Outperforms the Real Thing [Internet]. [cited 2022 Oct 17]. Available from: https://today.duke.edu/2022/08/lab-made-cartilage-gel-outperforms-real-thing