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Knee Injections to Replace Cartilage

Many surgical and non-surgical treatment options are available for conditions affecting the knee such as osteoarthritis. These may include weight loss, arthroscopy, physical therapy, and injection therapy; whether surgical or non-surgical, physiotherapy with low impact exercises is often recommended. However, some individuals also require the help of drug therapy to improve their pain, inflammation, and quality of life.

The medications which are most commonly prescribed for knee osteoarthritis include non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, and corticosteroids, which may be given as pills or Intraarticular injections. Individuals with refractory pain may also be advised opioids and heavy analgesics. (1) But it’s important to keep in mind that most of these medications can lead to adverse effects when used in the long term.

Knee Cartilage and Osteoarthritis

The knee’s cartilage consists of an extracellular matric and an intracellular matrix. The extracellular matrix of articular cartilage is mainly made up of a collagen framework and water. The collagenous framework consists of Glycosaminoglycans, proteoglycans, and hyaluronic acid. A proteoglycan of clinical importance is known as Aggrecan, which is a cartilage-specific proteoglycan core protein. This binds to the hyaluronic acid found in the cartilage and promotes properties like increased compressibility and elasticity in the cartilages.

In a healthy individual, the molecular size, shape, and volume of hyaluronic acid in the Synovial fluid may remain the same throughout life. However, certain conditions can accelerate the drop in concentration of Hyaluronic acid as an individual age. This may affect the elastic and viscous properties of the synovial fluid, which makes it viscous and non-elastic.

One of the first changes seen in Osteoarthritis of the knee is the destruction of Aggrecan by the enzyme known as aggrecanases. This leads to erosion of the cartilage. These changes in the extracellular matrix may also lead to a reduced concentration of hyaluronic acid molecules in the knee cartilage. (2)

A diagram of knee cartilage degeneration

Who needs knee injections to replace cartilage?

Knee injections may be recommended for individuals who have been taking over-the-counter pain killers or prescription medicine for a long time without seeing any improvement in the symptoms of their knee arthritis. These individuals may be recommended injections for the knee, with hyaluronic acid being the most recommended component. Individuals with moderate to severe knee pain may also be good candidates for knee injections when they walk or climb stairs. However, it is important to evaluate that the individual does not have any extensive alignment or mechanical issues with their knees, as the knee injections may prove to be ineffective for such individuals. In these cases they may be recommended knee replacement surgery.

Types of Knee Injections to Replace Cartilage –

Hyaluronic Acid

Hyaluronic injection, also called gel knee injections or viscosupplementation of the knee, is primarily composed of hyaluronic acid as their primary content. Hyaluronic acid is a natural substance found in the Synovial fluid of the joints. This therapy effectively treats joint pain and has a low chance of side effects. The common brands which make these gel injections include Synvisc, Euflexxa, Supartz, Orthovisc, ProVisc, and Hylagan.


Platelet-Rich plasma, which may also be referred to as PRP injections, contains several beneficial growth factors like tissue growth, insulin-like growth, platelet-derived, vascular endothelium, fibroblast, and epidermal growth factors. In addition, the injection of PRP into the knee joint leads to the promotion of homeostasis and range of motion. (8) This method is particularly found to affect the Wnt/β-catenin pathway, which is a cause of the development of Osteoarthritis.


MSC treatment or cell therapy comprises Intraarticular injections to promote stem cell formation in the joints. MSCs are naturally found in different tissues in a healthy individual, including adipose tissues, muscles, synovial membrane, synovial fluid, and dermis. However, these cells are most commonly harvested from sites like bone marrow and adipose tissues in clinical practice. The injection of these cells in the knee joint helps prevent inflammation and apoptosis. Instead, it has a pro-angiogenetic effect. (9)

Steroid Injections

Steroid injections, or cortisone injections, are another form of therapy that is effective for knee osteoarthritis. This is because the steroid that enters the intraarticular region of the knee joint helps promote immunosuppression at varying intensities of the inflammatory activity. An example of its immunosuppressive effects is its ability to block the production of pro-inflammatory cytokines and other signalling molecules, which initiate and promote inflammatory activity. An example of this is Interleukin 1, leukotriene, and proteins like metalloproteinase and leukotriene. This is the reason behind pain relief often encountered by individuals treated with steroid injections. (11)

Prolotherapy Injections 

The safest and most effective injections to replace cartilage are Prolotherapy Injections.

Prolotherapy is a treatment that involves the injection of a regenerative solution.

Cartilage hasn’t got a blood supply, so it doesn’t receive a direct supply of oxygen and nutrients in the same way that many other parts of the body do. Prolotherapy is a natural injection that helps to provide this supply of oxygen and nutrients with the aim of promoting cartilage regeneration.

It has been shown in studies to stimulate the production of chondrocytes, which are the cells the body uses to repair and regenerate cartilage.

In addition to this, Prolotherapy helps to strengthen and repair ligaments and tendons in the knee that may be under strain from compensating for the articular cartilage damage.

The injections also have immediate anti-inflammatory and painkilling benefits.

Combined Therapies

An orthopaedic surgeon or a health professional may opt for combined therapies to treat the joint pain associated with reduced production of synovial fluid of increased inflammatory activity. The combined therapy involves the use of intraarticular injection of multiple substances. These may include hyaluronic acid, MSCs, PRP, or corticosteroids. Studies have shown that individuals given a combination of these injections have superior results compared to those giving them a solo injection of hyaluronic acid. These combined therapies help reduce the pain associated with knee osteoarthritis, with both short-term and long-term outcomes. (10)

Frequently Asked Questions

How long do cartilage Injections Last?

Cartilage injections usually last between 5 weeks to 13 weeks. However, this period may be elongated by using a multiple injection regimen compared to a single injection. When additional injections are administered under the supervision of an orthopaedic surgeon or other health professionals, the individual may be able to have pain relief for as long as three years.

Can you Inject cartilage into the Knee?

Hyaluronic acid can be injected into the Knee, which helps boost the cartilage’s health and functioning. This is most commonly required in conditions like Osteoarthritis of the Knee, where the cartilage begins to thin, and the synovial fluid begins to disappear.

Can you Rebuild Knee Cartilage?

The cartilage in the knees itself has a limited capacity to rebuild or repair itself due to the insufficient blood supply. However, hyaluronic acid injections can help induce the growth of new cartilage and bone tissue in the joint. This may help the individual delay joint replacement surgery for joint damage.

What is the newest Knee Injection?

The FDA has approved new single injections and extended-release formulations for the Knee joint, which are effective for conditions like knee arthritis. The single injection hyaluronic acid-based injection includes Durolane and Bioventus, while the extended-release formulations include synthetic steroids like Acetonide.

Which Knee Injection is Best?

Amongst all the knee injections proposed to treat joint disorders in the past, hyaluronic acid injections are the most successful. These injections are also known as gel injections and effectively reduce joint pain and improve its overall functioning. Sometimes hyaluronic acid injection may also be guided by ultrasound.

Are Knee Injections Worth It?

Individuals who have been experiencing persistent pain in their joints with an increased level of inflammation may be recommended for knee injections. However, it is important to remember that most of these injections are effective for the short term and may need to be re-administered after a time recommended by the healthcare professional.

Further information about Hyaluronic Acid

When the hyaluronic acid gel injections are injected into the knees, they are proposed to work by promoting the lubrication and cushioning of the joints as they move. However, the pain experienced by individuals with arthritis and other joint disorder is most commonly caused by a lack of lubrication and cushioning effects, which leads to a greater frictional force being exerted every time an individual walks or bends their Knee. Therefore, for chronic pain affecting the Knee, the individual may be recommended to go for multiple injections in their Knee, which may be administered with a gap of 1 week in between.

The common reason hyaluronic acid injections of the Knee are recommended over oral supplements for Osteoarthritis is that the oral supplements may be poorly absorbed from the gut. (3)

The effect of hyaluronic acid injections has been studied in numerous clinical trials, which have involved the participants being administered the intra-articular hyaluronic acid injections. Most of these studies showed that these gel injections could help the direct augmentation of synovial fluid and its elasticity. However, it is important to note that these effects are short-lived due to the half-life of Hyaluronic acid being only 48 hours. Hence due to the short-term viscosupplementation, hyaluronic acid injections may be required to be administered again and again. (4)

Studies have also shown that when intra-articular injection of Hyaluronic is given, it causes the high molecular hyaluronic acid accumulates in the subchondral bone and the cartilage. This accumulation prevents the degradation of knee cartilage and promotes its stability and regeneration. The molecular weight of the hyaluronic acid injected into the knees is important in determining its effects on the knee joint. The formulas with a higher molecular weight are usually able to retain a greater amount of water in the articular space. These also have a more efficient anti-inflammatory role and prevent the production of pro-inflammatory cytokines like bradykinin and Prostaglandins. (5)

Benefits of Hyaluronic Acid in the Knee Joint

Synovial fluid is important for the healthy functioning of joints. The primary element found in Hyaluronic acid, which gives it its specific functions, is the polysaccharide chains made with a molecular weight of 4 to 8 million Da. It is composed of N-acetylglucosamine and glucuronic acid, which the Synoviocytes and chondrocytes produce. A healthy knee joint consists of at least 2 ml of synovial fluids, with a concentration of hyaluronic acid of between 2.5 to 4 mg per ml.

When an individual moves their joint, the hyaluronic acid acts as a shock absorber and lubricant, which helps protect the joint’s articular cartilage and other structures. This help reduces the wear of articular cartilages due to the shear and compression forces induced on them. Another benefit of Hyaluronic acid on the joints is its supplication of oxygen and nutrients to the surrounding tissues meanwhile removing metabolic waste and carbon dioxide.

The properties of hyaluronic acid in the joint depend on its molecular weight and the concentration found inside the joint. When an individual undergoes fast-paced exercises, the hyaluronic acid found in the cartilages does not get adequate time to realign its chains and keep acting as a lubricant. On the other hand, the slower movement of the joint causes a slow movement and lower shear forces on the cartilage, which allows the chains of hyaluronic acid to get adequate time to align themselves in the direction of the flow get vicious and promote the action of shock-absorbing proteins. (6)

Hyaluronic acid also exhibits anti-inflammatory effects in the joints. This improves the full pain symptoms associated with joint diseases like Osteoarthritis. This is proven by studies that have shown hyaluronic acid to reduce the rate of leucocyte adherence, phagocytosis, production of pro-inflammatory mediators, and release of arachidonic acid from the fibroblasts of the synovial tissues. (7)

Side effects of knee injections to replace cartilage

While there are many proven benefits of injections for the Knee, it also comes with its fair share of side effects. While some individuals may experience slight irritation after hyaluronic acid injections, they are considered much safer than corticosteroid injections. The side effects associated with corticosteroid injections include:

·         Temporary soreness

·         Temporary swelling at the injection site

·         Temporary bruising at the injection site

·         Temporary irritation and itching of the skin surrounding the knee

In the majority of the cases, the knee injection side effects resolve within a few days. However, if these symptoms increase with every passing day or the individuals start to experience breathing difficulties and skin rashes, they should consult a physician immediately. When injections are no longer possible for the individual due to many side effects, they may be considered for joint replacement. However, this is considered the last resort.


1.       Goldberg, V. M., & Goldberg, L. (2010). Intra-articular hyaluronans: the treatment of knee pain in Osteoarthritis. Journal of pain research, 3, 51–56. https://doi.org/10.2147/jpr.s4733

2.       Moreland L. W. (2003). Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of Osteoarthritis: mechanisms of action. Arthritis research & therapy, 5(2), 54–67. https://doi.org/10.1186/ar623

3.       du Souich P. (2014). Absorption, distribution and mechanism of action of SYSADOAS. Pharmacology & therapeutics, 142(3), 362–374. https://doi.org/10.1016/j.pharmthera.2014.01.002

4.       Brown, T. J., Laurent, U. B., & Fraser, J. R. (1991). Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Experimental physiology, 76(1), 125–134. https://doi.org/10.1113/expphysiol.1991.sp003474

5.       Abate, M., and V. Salini. “Osteoarthritis-Diagnosis, Treatment and Surgery.” (2012).

6.       Henrotin, Y., Raman, R., Richette, P., Bard, H., Jerosch, J., Conrozier, T., Chevalier, X., & Migliore, A. (2015). Consensus statement on viscosupplementation with hyaluronic acid for the management of Osteoarthritis. Seminars in arthritis and rheumatism, 45(2), 140–149. https://doi.org/10.1016/j.semarthrit.2015.04.011

7.       Snibbe, J. C., & Gambardella, R. A. (2005). Use of injections for Osteoarthritis in joints and sports activity. Clinics in sports medicine, 24(1), 83–91. https://doi.org/10.1016/j.csm.2004.08.001

8.       Sun, Y., Feng, Y., Zhang, C. Q., Chen, S. B., & Cheng, X. G. (2010). The regenerative effect of platelet-rich plasma on healing in large osteochondral defects. International orthopaedics, 34(4), 589–597. https://doi.org/10.1007/s00264-009-0793-2

9.       Di Matteo, B., Vandenbulcke, F., Vitale, N. D., Iacono, F., Ashmore, K., Marcacci, M., & Kon, E. (2019). Minimally Manipulated Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Systematic Review of Clinical Evidence. Stem cells international, 2019, 1735242. https://doi.org/10.1155/2019/1735242

10.   Smith, C., Patel, R., Vannabouathong, C., Sales, B., Rabinovich, A., McCormack, R., Belzile, E. L., & Bhandari, M. (2019). Combined intra-articular injection of corticosteroid and hyaluronic acid reduces pain compared to hyaluronic acid alone in the treatment of knee osteoarthritis. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 27(6), 1974–1983. https://doi.org/10.1007/s00167-018-5071-7

11.   Mora, J. C., Przkora, R., & Cruz-Almeida, Y. (2018). Knee osteoarthritis: pathophysiology and current treatment modalities. Journal of pain research, 11, 2189–2196. https://doi.org/10.2147/JPR.S154002

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