Regenerative Medicine in Orthopaedics: Where Do PRP, Prolotherapy and Viscosupplementation Fit?

"Regenerative medicine" is one of the most talked-about areas in orthopaedics. Patients increasingly ask about platelet-rich plasma (PRP), prolotherapy and "gel" injections for their knees, tendons and backs, often after seeing them advertised as natural, drug-free ways to heal damaged tissue and avoid surgery.

Some of that interest is justified. These treatments are generally safe, they make biological sense, and some patients do benefit. But the evidence is more mixed than marketing suggests, results vary between conditions and between individuals, and they are not a cure for worn-out joints.

This article explains what each treatment is, where it may have a role, what the research currently shows, and how to decide whether one might be appropriate for you.

Key takeaways

• PRP, prolotherapy and viscosupplementation are injection treatments that aim to reduce pain and support the body's own healing or joint function.
• The evidence varies by treatment and by condition. For some uses the evidence is encouraging; for others it is limited or conflicting.
• These treatments do not regrow cartilage or reverse arthritis in any reliable, proven way.
• They work best as part of a wider plan that includes exercise, weight management and activity changes.
• Patient selection matters. The right treatment depends on the diagnosis, severity, goals and what has already been tried.

What do we mean by "regenerative medicine"?

In orthopaedics, "regenerative" or "orthobiologic" treatments are therapies that try to influence the body's own repair processes rather than simply suppressing pain or inflammation. The three most commonly discussed injection treatments are:

1. Platelet-rich plasma (PRP), a concentrate of platelets from your own blood
2. Prolotherapy, injection of an irritant solution, usually concentrated dextrose (sugar), to stimulate a healing response
3. Viscosupplementation, injection of hyaluronic acid into a joint to supplement its natural lubricating fluid

Cell-based treatments, often marketed as "stem cell" therapy, are a separate category. Their evidence base is still at an early stage, and they are outside the scope of this article, except to say that patients should be cautious about clinics offering unproven cell treatments at high cost.

Platelet-rich plasma (PRP)

What it is

Platelets are best known for their role in blood clotting, but they also release growth factors and signalling proteins involved in tissue repair. To make PRP, a small amount of your own blood is drawn and spun in a centrifuge, which separates it into layers. The platelet-rich layer is collected and injected into the injured or painful area, often under ultrasound guidance.

Because PRP comes from your own blood, the risk of allergic reaction is very low. The main side effects are temporary pain and swelling at the injection site.

Where it may have a role

PRP has been studied in many conditions, including:

• Knee osteoarthritis, particularly mild to moderate disease
• Chronic tendon problems (tendinopathies), such as tennis elbow and some patellar and Achilles tendon problems
• Plantar fasciitis
• Some muscle and ligament injuries

What the evidence shows

The evidence for PRP is genuinely mixed, and it differs between conditions.

For knee osteoarthritis, the American Academy of Orthopaedic Surgeons (AAOS) 2021 guideline states that PRP may reduce pain and improve function, with the strength of recommendation graded as limited [1]. However, a well-designed randomised trial published in *JAMA* in 2021 found that PRP injections did not result in a significant difference in knee pain or cartilage volume compared with placebo injections at 12 months in patients with mild to moderate knee osteoarthritis [2].

For soft tissue injuries more broadly, a Cochrane review concluded that there was insufficient evidence to support the routine use of platelet-rich therapies [3]. Research continues, and part of the challenge is that PRP preparations vary widely in platelet concentration, white cell content and injection protocol, which makes studies hard to compare.

Limitations

• Results vary between individuals, and it is not yet possible to predict reliably who will respond
• Preparations are not standardised
• It does not regrow cartilage in a proven, meaningful way
• It is usually not covered by insurance, and costs can add up with repeated injections

Prolotherapy

What it is

Prolotherapy (short for "proliferative therapy") involves injecting a solution, most commonly hypertonic dextrose, into ligaments, tendons or joints. The idea is that the solution causes a mild, controlled irritation that triggers the body's healing response and strengthens the injected tissue. Treatment usually involves a series of injections over several weeks or months.

Where it may have a role

Prolotherapy has been used for knee osteoarthritis, some tendon problems, and chronic low back pain related to ligaments.

What the evidence shows

Evidence for prolotherapy is limited. For chronic low back pain, a Cochrane review concluded that prolotherapy injections alone were not an effective treatment, although when combined with other treatments such as manipulation and exercise, some studies reported improvement [4]. For knee osteoarthritis and some tendon problems, a number of small studies have reported benefit, but larger, high-quality trials are needed before firm conclusions can be drawn.

Limitations

• The evidence base is smaller and of lower quality than for many other treatments
• Multiple injection sessions are usually needed
• Injections can be uncomfortable, and temporary post-injection pain is common

Viscosupplementation (hyaluronic acid injections)

What it is

Healthy joint fluid contains hyaluronic acid, which helps lubricate the joint and absorb shock. In osteoarthritis, the concentration and quality of hyaluronic acid in the joint fluid decreases. Viscosupplementation involves injecting hyaluronic acid into the joint, most commonly the knee, to supplement the natural fluid. It is sometimes described to patients as a "gel" or "lubricant" injection.

What the evidence shows

Viscosupplementation has been studied extensively in knee osteoarthritis, with conflicting results. A large systematic review and meta-analysis in *Annals of Internal Medicine* concluded that viscosupplementation was associated with a small and clinically irrelevant benefit on pain, and an increased risk of serious adverse events, in knee osteoarthritis [5]. The AAOS 2021 guideline states that hyaluronic acid injection is not recommended for routine use in symptomatic knee osteoarthritis (moderate strength of recommendation) [1].

That said, some patients report meaningful relief, and some clinicians consider it in selected cases, for example when other treatments are unsuitable or have not helped. The key words are "not routine": it should be a considered decision rather than a default.

Comparing the three at a glance

• PRP: your own concentrated platelets. Used for knee osteoarthritis and chronic tendinopathies. Evidence is mixed: some guidelines describe possible benefit, while high-quality trials show conflicting results.
• Prolotherapy: a dextrose irritant solution, given as a series of injections. Used for ligament, tendon and joint pain. Evidence is limited, from mostly small studies.
• Viscosupplementation: hyaluronic acid injected into the joint. Used for knee osteoarthritis. Major reviews show small benefit on average, and it is not recommended for routine use.

Why these treatments are not a cure for arthritis

It is important to be clear about what these treatments can and cannot do. Osteoarthritis involves the gradual loss of cartilage, changes in the underlying bone and inflammation of the joint lining. No injection has been reliably shown to regrow lost cartilage or reverse these changes. At best, these treatments may reduce pain and improve function for a period of time.

Treatments that address the whole joint and the whole person remain the foundation of care for osteoarthritis:

• Strengthening exercise, particularly of the thigh and hip muscles
• Weight management, which reduces load on the knees
• Activity modification and pacing
• Appropriate pain relief
• Joint replacement for advanced arthritis that severely limits daily life

Who might be a candidate?

Regenerative injections may be worth discussing if:

• You have a confirmed diagnosis that matches the treatment, such as mild to moderate knee osteoarthritis or a chronic tendinopathy, rather than undiagnosed pain
• You have already engaged in an appropriate exercise and rehabilitation programme
• You understand that results vary, and have realistic expectations
• You are not a candidate for, or wish to delay, other treatments
• There are no contraindications, such as active infection, certain blood disorders or, for PRP, use of specific medications

They are less likely to help in very advanced arthritis with severe joint damage, where a joint replacement may be the more effective option.

Why individualised treatment matters

The most important principle in regenerative medicine is that there is no one-size-fits-all injection. A responsible approach involves:

1. Accurate diagnosis, through history, examination and appropriate imaging, often including ultrasound
2. Grading severity, because what may help in early disease is unlikely to help in end-stage disease
3. Discussing all options, including exercise, weight management, standard injections and surgery, not only regenerative ones
4. Honest discussion of the evidence, likely benefit, costs and alternatives
5. Precise delivery, often under ultrasound guidance, so the injection reaches the intended target
6. Combining with rehabilitation, since injections are rarely effective on their own
7. Measuring outcomes, and stopping treatments that are not helping

Questions to ask before having a regenerative injection

• What exactly is my diagnosis, and how severe is it?
• What does the research show for this treatment in my specific condition?
• What are the alternatives, including non-injection options?
• How many injections are recommended, and what is the total cost?
• Will the injection be guided by ultrasound?
• How will we know whether it has worked, and what is the plan if it doesn't?

Frequently asked questions

Can PRP regrow cartilage in my knee?

There is no reliable evidence that PRP regrows cartilage in a meaningful way. Its potential benefit is in reducing pain and improving function for some patients.

Are these treatments safe?

They are generally safe when performed correctly under sterile conditions. Temporary pain and swelling after injection are common. As with any injection, there is a small risk of infection.

How long do the effects last?

This varies by treatment, condition and individual. Where there is benefit, it is typically measured in months rather than years, and some patients do not respond.

Are they better than a steroid injection?

They work differently. Steroid injections provide faster but often shorter-term relief of inflammation. Regenerative injections aim for a different biological effect. The best option depends on your diagnosis and circumstances.

The bottom line

PRP, prolotherapy and viscosupplementation have a place in modern orthopaedic care, but it is a defined and limited place. They are not miracle cures, they do not reverse arthritis, and the evidence for each varies by condition. Used thoughtfully, for the right patient, with honest expectations and alongside exercise and rehabilitation, they can be a useful option. Used indiscriminately, they add cost without benefit. The key is an accurate diagnosis and an individualised plan.

References

1. American Academy of Orthopaedic Surgeons. Management of Osteoarthritis of the Knee (Non-Arthroplasty): Evidence-Based Clinical Practice Guideline. 2021.
2. Bennell KL, et al. Effect of intra-articular platelet-rich plasma vs placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial. JAMA. 2021.
3. Moraes VY, et al. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev. 2014.
4. Dagenais S, et al. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst Rev. 2007.
5. Rutjes AW, et al. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012.