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Caring Medical
Regenerative Medicine Clinics

Chicagoland office
715 Lake Street, Suite 600
Oak Park, IL 60301
708.393.8266 Phone

Southwest Florida office
9738 Commerce
Center Court
Fort Myers, FL 33908
239.303.4069 Phone

855.779.1950 Fax

Alternatives to Knee Surgery and Knee Replacement

Ross.Hauser.MDIn this article Ross Hauser MD discusses knee replacement research and knee surgery alternatives.

For many years now, state of the art management of knee osteoarthritis treatment was a total or partial knee replacement.  Over the past few years the medical community has begun an awkward shift away from surgery towards “biomedicine” and the use of patient’s stem cells and blood platelets as healing mechanisms.

At Caring Medical Regenerative Medicine Clinics, we specialize in pain cures, not pain management. As such we always research, write our own research, and explore new methodologies to curing knee pain.

In this article we suggest:

        • Surgery for many defects of the knee is not the first option we would choose.
        • Stem Cell Therapy, Platelet Rich Plasma Therapy, Prolotherapy are viable alternatives to Knee Surgery and Knee Replacement
        • As risk of complications rates from knee surgery rise, patients should be offered non-surgical options

For many years now, state of the art management of knee osteoarthritis treatment was a total or partial knee replacement.  Over the past few years the medical community has begun an awkward shift away from surgery towards “biomedicine” and the use of patient’s stem cells and blood platelets as healing mechanisms.

The Needle Cures

The shift away from surgery to biomedicine injections has some saying that patients get better because of a placebo effect. Many studies have shown that injecting a needle, even a dry needle causes many patients to “get better.” This is the placebo effect. But is it really a placebo?

In January of 2015 doctors examined the placebo effect on patients suffering from knee osteoarthritis. Not included in the study were Prolotherapy, Platelet Rich Plasma Therapy, or Stem Cell Therapy.

Here is what they did: They provided patients with the following acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib (see our article on how painkillers can increase pain), intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and intra-articular placebo.

After three months of testing they found  Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs, possibly because of the integrated “injection” placebo effect.

All treatments except acetaminophen showed clinically significant improvement from baseline pain. 1

  • So clearly giving an injection makes the patient feel better

For some doctors, injection therapy goes beyond placebo, injection therapies for regenerating knee tissue is state of the art management of knee osteoarthritis.

In May of 2015 doctors found that Platelet Rich Plasma Therapy is a viable treatment for knee osteoarthritis and has the potential to lead to symptomatic relief for up to 12 months.2

In February 2015, a new research paper called: “State-of-the-Art management of knee osteoarthritis” outlined treatment strategies for knee osteoarthritis. Here are the summary highlights with treatment suggestions:

At the top

  • Patients should be advised that painkillers and anti-inflammatories that while commonly used  for managing knee osteoarthritis, can be effective in the short-term but are less effective for long-term management. Additionally, more prolonged use significantly increases the risk of serious associated side effects that are not too uncommon.
  • Disease-modifying osteoarthritis drugs need to be further investigated for their effectiveness.

The goal of developing new treatment strategies for knee osteoarthritis is to prolong the need for total knee replacement  which should be utilized only if other strategies have failed.

High tibial osteotomy (cutting and reshaping of the bone) and unicompartmental knee arthroplasty (partial knee replacement) are potential alternatives if only a single compartment is involved with more data supporting unicompartmental knee arthroplasty as a good treatment option in this scenario.

Arthroscopy has been commonly used for many years to treat knee knee osteoarthritis to address degenerative articular cartilage and meniscus, however, several high-quality studies have shown that it is not a very effective treatment for the majority of cases and should generally not be considered when managing knee osteoarthritis. From “State-of-the-Art management of knee osteoarthritis

Then Why Were You Recommended for Knee Replacement Surgery?

There are several reasons why your doctor may recommend knee replacement surgery. Recently, the American Academy of Orthopaedic Surgeons published general criteria which included the following reasons:

  • Patients with bowed knees
  • Patients in severe pain
  • Patients with knee stiffness that limits everyday activities
  • Patients with chronic knee inflammation and swelling that does not improve with rest or medications
  • Patients who failed to have symptoms improve with anti-inflammatory medications, cortisone injections, lubricating injections, physical therapy, or other surgeries.

From another perspective, when asked why they considered a total knee replacement, patients responded in survey research that they wanted an improvement in pain, a restoration of function, i.e., walking, stair climbing, and the ability to move without assistive devices.

Recently doctors tried to come up with a formula that would better allow them to predict who would have knee replacement and subsequent revision knee replacement surgery failure.

Who was most at risk?

  • Patients who had tibial tuberosity osteotomy (bone realignment surgery)
  • Patients with kidney faliure
  • Patients with rheumatic diseases
  • Patients who had Posterior-stabilized constrained total knee arthroplasty for complex primary cases
  • Patients who had to have the revision surgery within 5 years of the first surgery
  • Patients with septic loosening.3

At Caring Medical Regenerative Medicine Clinics we specialize in pain cures, not pain management. As such we always research, write our own research, and explore new methodologies to curing Knee Pain. Coming up on our twentieth year in practice, we can still safely say that surgery for many defects of the knee is not the first option we would choose. Why? Because we have found and shown in research that Prolotherapy is effective for curing knee pain.

Does Knee Replacement Meet Patient Expectations?

To be fair, we wanted to report on some positive outcomes and knee surgery success rates:

Arthroscopic joint debridement is a potential treatment for knee osteoarthritis. . . This procedure results in an excellent or good outcome in approximately 60 % of patients in approximately 5 years.4

Joint debridement is a sort of “power-washing” of the joint to wash away loose tissue and other loose bodies in the joint. Sixty percent patient satisfaction is good unless you are in the other 40%.

 One Third of Knee Replacements Inappropriate

Over the years we have reported that we have seen many patients following knee replacement surgery who still had pain. After an examination we could clearly see that some of the patients did not need the surgery and that their doctors may have had an over zealousness to get them onto the operating table. That has been our opinion for years and many times we would get the casual email saying that we were off base to offer such an opinion.

On June 30, 2014, a press release was issued from the medical journal Arthritis & Rheumatology, in it doctors say that their research suggests that more than one third of total knee replacements in the U.S. were “inappropriate.” Using a patient classification system developed and validated in Spain the study highlights the need for consensus on patient selection criteria among U.S. medical professionals treating those with the potential need of knee replacement surgery.

The Agency for Healthcare Research and Quality reports:

  • more than 600,000 knee replacements are performed in the U.S. each year.
  • In the past 15 years, the use of total knee arthroplasty has grown significantly
  • Some experts believe the growth is due to use of an effective procedure, while others contend there is over-use of the surgery that relies on subjective criteria.

The present study led by Dr. Daniel Riddle from the Department of Physical Therapy at Virginia Commonwealth University in Richmond, examined the criteria used to determine the appropriateness of total knee arthroplasties. “To my knowledge, ours is the first U.S. study to compare validated appropriateness criteria with actual cases of knee replacement surgery,” said Dr. Riddle.

“Our finding that one third of knee replacements were inappropriate was higher than expected and linked to variation in knee pain osteoarthritis severity and functional loss. These data highlight the need to develop patient selection criteria in the U.S.,” concludes Dr. Riddle.

In a related editorial, Dr. Jeffery Katz from the Orthopedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital in Boston, Mass., writes, “I agree with Riddle and colleagues, and with Escobar and colleagues, that we should be concerned about offering total knee replacements to subjects who endorse “none” or “mild” on all items of the pain and function scales.”

Pain After Total Knee Replacement

A main reason for knee pain after knee replacement is ligament instability. Ironically, the number one symptom that prolotherapy, platelet rich plasma, and stem cell therapy  address in pre-surgery patients is ligament instability. This is the cause of pain that we point out to patients – knee ligament instability before and after total knee replacement. Perhaps the answer to their problem should have been to treat the ligaments! Not replace the knee!

Here is what the literature says:

  • “Instability is one of the most common causes of failure of total knee arthroplasty (TKA)…Acute instability is related to intraoperative injuries or excessive release of important coronal stabilizers such as the medial collateral ligament in extension or the posterolateral corner in flexion.” (Note – the surgery itself caused instability!)5
  • “In 32.6 % of all cases [requiring a revision surgery], ligament instability was the primary reason for revision. In another 21.6%, ligament instability was identified as a secondary reason for revision. Analysis of the different instability forms showed combined instability in extension and flexion as the most common cause, followed by isolated instability in flexion (31.8%) and isolated instability in extension (9.1%).6  The high correlation between instability and malpositioning of the prostheses was obvious.”

Please see the companion article treating patients with pain after knee replacement surgery on our site.

For women and older patients, the chances of a successful knee replacement are lower

In a study out of London, researchers sought to uncover various predictors of a successful (or unsuccessful) outcome in a total knee replacement2. Looking at 1,991 total knee replacement patients over a three-year period, they discovered various predictors of poor outcomes. Among the findings were that females and older people had worse functional outcomes following the replacement surgery.

While women should take this information into account, any Prolotherapist would argue that all knee osteoarthritis patients should seek a second opinion from a Prolotherapist to see if they can avoid surgery and its potential adverse outcomes.

At Caring Medical and Rehabilitation Services, (CMRS), we have found and shown in research that Prolotherapy is effective for curing knee pain.7

Knee replacement given to patients with low back and hip pain

In a recent study, investigators advised doctors that they must recognize hip disease before giving a recommendation for back and knee surgery because doctors may be performing the wrong procedures. Writing in the medical journal Modern Rheumatology, they say: “We suggest that rheumatologists be aware of hip disease masquerading as knee pain or low back pain.”8

They noted various ways hip pain distributes itself:

Distribution of pain originating in the hip was:

  • 89 % to the groin
  • 38 % to the buttock
  • 33 % to the anterior thigh
  • 29 % to the knee
  • 27 % to the greater trochanter
  • 17 % to the low back
  • 8 % to the lower leg

In the case of chronic joint pain, a thorough examination is imperative in identifying the correct diagnosis. That sounds like common sense, but the sad truth is that the source of pain is often missed. Let’s take a look at some recent research.

Minimally Invasive Knee Replacement Surgery

There recently has been increased interest in soft-tissue sparing total knee arthroplasty (TKA). Reports have advocated reduction in the size of the incision, disruption to the joint and relative preservation of the quadriceps tendon. Some studies have even suggested decreased blood loss, transfusion rates, and hospital length of stay using these techniques. However, enthusiasm for the potential advantages of this approach is tempered by the possibility of increased complication rates.9

This study was conducted in 2008, certainly things have changed with the upgrades in technique and technology to assist the surgeon. BUT maybe not – In July 2013 published research – listen to what these researchers said: even after the surgeon completed a substantial number of cases before the commencement of this study, using computer-assisted navigation to preserve the quadriceps tendon gave inferior results (documented on MRI) and longer operating time.10

Let’s point out here that this technique is designed to spare the quadricep muscles and tendons from damage and destruction caused by the surgery, not the injury itself!

 One study identifies 22 different risks associated with total knee arthroplasty

Here is what the authors had to say:

“The 22 TKA complications and adverse events include:

  • bleeding,
  • wound complication,
  • thromboembolic disease,
  • neural deficit,
  • vascular injury,
  • medial collateral ligament injury,
  • instability,
  • malalignment,
  • stiffness,
  • deep joint infection,
  • fracture,
  • extensor mechanism disruption,
  • patellofemoral dislocation,
  • tibiofemoral dislocation,
  • bearing surface wear,
  • osteolysis,
  • implant loosening,
  • implant fracture/tibial insert dissociation,
  • reoperation,
  • revision,
  • readmission,
  • and death.”11

Another surgical complication involves difficulty in performing secondary surgery. In another study, researchers looked at patients who had a prior procedures including bone procedures, high tibial osteotomy, tibial plateau fracture, patellar realignment, and arthroscopy. They discovered that prior knee surgery could be considered a clinical condition that predisposes a patient to postoperative complications with a total knee replacement. After analyzing three groups of patients they found that patients who underwent arthroscopy and meniscectomy had a higher rate of postoperative local complications than patients with no prior surgery or procedures. Further, they found that patients with prior bone procedures showed the poorest postoperative abilities in knee flexion and showed the greatest need for extended surgical approach.12

Bone surgery for the knee

As the knee degenerates, it changes in shape. A popular treatment involves restoring the shape by bone surgery to alleviate pressure and pain. Osteotomy is a surgery that the researchers say, “should always be performed if possible.”13

When a surgeon recommends an osteotomy for the knee the goal is that they can change the shape or slope or angle of the bone to realign the knee to relieve pressure on the pain causing part of the knee by distributing your weight to a sturdier part of your knee. The hope of course is to extend the life of your real knee and delay knee replacement surgery. Surgery to avoid surgery!

Problem is –
1) You are removing anatomy, as we like to say, if you didn’t need it, it wouldn’t be there in the first place.
2) Extended recovery time and immobility.
3) If the Osteotomy does not work, a knee replacement is next and unfortunately, total knee replacement is a much more complicated surgery with some bone missing or altered. This complication is why knee replacement is usually called for from the start.

So why always perform this surgery if possible? Because there is a chance by altering the knee that knee cartilage can regenerate! In fact it has been reported in 60% of cases following high tibial osteotomy that there has been some degree of cartilage regeneration.

Prior procedures that damaged the knee

The saline used in many medical procedures actually damages articular cartilage. “Normal saline, the most commonly used irrigation fluid, may have an inhibitory effect on proteoglycan metabolism in articular cartilage. Additional studies are required to assess the potential damage to cartilage from normal saline in the clinical setting.”14

This  medical research paper was published in December 2012. Interestingly ,way back in 1991, similar concerns were noted: “[It is suggested] that meniscal damage may occur as a direct result of using normal saline for irrigation during knee arthroscopy.”15

Problem 2: Loss of knee fluid

Remarkably, about twenty years later, one paper noted: “The short-term recovery period post-arthroscopic meniscectomy is characterized by pain and impaired function most likely related to the irrigation of synovial fluid from the knee intraoperatively. Consequently, along with removal of harmful debris, the irrigation fluid dilutes the hyaluronic acid layer covering the joint tissues. Hyaluronic acid contributes to the homeostasis of the joint environment and is an important component of synovial fluid and cartilage matrix. Hence, the instillation of hyaluronic acid after the procedure may relieve symptom. “16

In concept, replacing hyaluronic acid makes sense. If the surgery is causing loss of natural hyaluronic acid, then replacing it after surgery should help. For some it reduced pain ,but  it did NOT improve knee function for all. As a side note – which patients were excluded from the study? “Patients with ligamentous injuries or severe chondral damage were excluded.”17 These patients are those who seemingly would benefit the most from Comprehensive Prolotherapy.

Cartilage Transplant

The word autologous means it comes from you. If you receive an autologous stem cell treatment, this means that stem cells were taken from your body. This is the basis of “biomedicine.” Using your blood or stem cells to heal you.

Yet, stem cell therapy is often combined with much more radical procedures, namely those found in surgery. Here is new research which acknowledges that repairing damaged cartilage is a major goal of musculoskeletal tissue engineering. But in this study, there is a need for a cartilage patch, a flap of skin over the cartilage lesion to make stem cells work.

“Allogeneic (same species, different individual) or xenogeneic (different species) sources can provide an attractive source of chondrocytes for cartilage tissue engineering, since autologous (same individual) cells are scarce.”18 Meaning that there is not enough cartilage in the patient to make skin flaps.

The problem with going outside the patient to another human being or animal to get cartilage tissue is the idea of immune rejection of non-autologous cartilage. In this research the investigators suggest that human to human cartilage transplant is possible with associated variables to limit rejection.

Here again, is an expansion of the simple basics of stem cell therapy into the surgical theater.

Alternatives to Knee Surgery and Knee Replacement

For a patient researching alternative treatments for knee surgery, especially a patient who has had many failed treatments and procedures, the one new thing that will keep coming to the top of their search is stem cell treatments, specifically bone marrow-derived mesenchymal stem cells.

Mesenchymal stem cells represent one of the new technologies in medicine, so much so that many different treatment modality specialists want to incorporate their usage into their scope. Surgeons want it, synvisc doctors want it, Prolotherapy doctors want it. Why? Read the research on stem cells, osteoarthritis and cartilage regeneration:

Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury.

The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because cartilage has a poor blood supply and therefore poor healing abilities. Although surgical and pharmaceutical interventions are currently available for treating osteoarthritis, restoration of normal cartilage function has been difficult to achieve. [In other words surgery and pharmaceuticals are not working]. . . . Bone marrow-derived ‘mesenchymal stem cells’ with inherent chondrogenic differentiation potential [Stem cells can morph into cartilage cells] appear to be ideally suited for therapeutic use in cartilage regeneration.”19

Stem Cell Therapy for Articular Cartilage Regeneration

This regeneration potential is why the Prolotherapy doctors want to use stem cells. In Prolotherapy, ligaments and tendons are treated to stabilize the knee joint and prevent excessive movement that could cause pain in the bone on bone situation. If you add stem cells to the treatment protocol you are not only repairing the ligaments and tendons, but also the cartilage in a non-surgical manner.

The results have been very promising, so much so that the other orthopedic specialties have noticed that the introduction of stem cells seem to make their procedures go a little better. Even the surgeons have joined in:

In surgery, the stem cell technique require some form of scaffolds (a patch) and two separate surgical procedures. One research paper was happy to announce that they did not need acartilage patch and eliminated one of the surgeries.20  It is interesting to note that a high advance would be the scaffold-less approach – in other words – a piece of tissue from healthy cartilage transported to the site of the damaged cartilage. In Bone Marrow Prolotherapy the scaffold-less approach is how it is done! In this study success was cited as only a single operation as opposed to two and they even speculate that stem cells would be superior to autologous chondrocyte implantation (ACI) and aid in Hyaluronic Acid effectiveness. The question has to be asked, why have the surgery, why have the autologous chondrocyte implantation, why have the Synvisc, if the stem cells are working well on their own? The one treatment that researchers are showing stem cells work well with is in a combined application with Platelet Rich Plasma Therapy.

Stem cell therapy to repair damaged knee cartilage

Further, “Despite its remarkable ability to resist mechanical loading, articular cartilage is not capable of mounting a useful reparative reaction in response to damage caused by trauma or disease. As a result numerous surgical and medical approaches have been developed to aid the healing of articular cartilage. Despite the success of surgical techniques such as microfracture, recently attentions have been turned to cell based therapies such as autologous chondrocyte implantation (ACI).”21

Despite the remarkable success the surgeons want something better than microfracture – perhaps the success was not as remarkable as they hoped. Back to autologous chondrocyte implantation (ACI) – “ACI has produced encouraging results, however better results may be achievable through an evolution of this surgical approach.” That would be the introduction of stem cells – and in agreement with the previous cited study about perhaps stem cells being more effcetive than ACI.21

In these cited studies, stem cells are looked upon to enhance surgical procedure and have been shown effective. In Bone Marrow Prolotherapy we like to show that the stem cells are effective enough that the surgery is not necessary. Like all injectable solutions used with Prolotherapy, Stem cells are used as an aid in healing and an alternative to surgery. The injections are designed to stimulate the repair of injured tissues. This is achieved through the rebuilding of the components of the ligaments, tendons, and cartilage in knees with moderate and advanced osteoarthritis.

Alternatives to Knee Surgery and Knee Replacement 

In our experience, even if a person has already had a surgical evaluation, it is well worth consulting a Prolotherapy and/or Platelet Rich Plasma Therapy and/or stem cell therapy. At Caring Medical, we specialize in Physical Medicine and Rehabilitation and has seen and treated thousands of patients who were on the path to surgery before avoiding it because of Prolotherapy, an injection technique that stimulates the body to repair the painful area.

For more information on Prolotherapy, Stem Cell Therapy, and Platelet Rich Plasma Therapy for the regrowth of knee articular cartilage and meniscus tissue, please refer to our article stem cell treatment for meniscus repair. See also our article on Arthroscopic knee surgery for osteoarthritis.

Prolotherapy for knee pain

As we have reported in previous articles, we have documented articular cartilage regeneration in the Journal of Prolotherapy utilizing dextrose Prolotherapy injections 22 Here is our summation:
“Prolotherapy improved the pain and function in five knees with osteoarthritis. All five degenerated knees showed evidence of articular cartilage regeneration in their standard weight-bearing X-rays after Prolotherapy. It is suggested that before and after X-ray studies can be used to document the response of degenerated joints to Prolotherapy.”

Prolotherapy is the only treatment found to stimulate cartilage repair and regeneration, as is shown by the X-rays. Furthermore, Prolotherapy offers the most curative results in treating chronic pain. It effectively eliminates pain because it attacks the source: the fibro-osseous junction, an area rich in sensory nerves. This improved tissue strength creates long term pain relief.

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1. Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015 Jan 6;162(1):46-54. doi: 10.7326/M14-1231.
2. Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR Jr, Cole BJ. Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared With Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review of Overlapping Meta-analyses. Arthroscopy. 2015 May 29. pii: S0749-8063(15)00353-9. doi: 10.1016/j.arthro.2015.03.041. [Epub ahead of print]
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7. Luque R, Rizo B, Urda A, Garcia-Crespo R, Moro E, Marco F, López-Duran L. Predictive factors for failure after total knee replacement revision. Int Orthop. 2014 Jan 9.
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9. Jackson G, et al. Complications Following Quadriceps-sparing Total Knee Arthroplasty. Orthopedics. June 2008 – Volume 31 · Issue 6
10. Lin SY, Chen CH, Fu YC, Huang PJ, Lu CC, Su JY, Chang JK, Huang HT. Comparison of the clinical and radiological outcomes of three minimally invasive techniques for total knee replacement at two years. Bone Joint J. 2013 Jul;95-B(7):906-10. doi: 10.1302/0301-620X.95B7.29694.
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13. Spahn G, Klinger H, Harth P, Hofmann GO. [Cartilage regeneration after high tibial osteotomy. Results of an arthroscopic study].Z Orthop Unfall. 2012 Jun;150(3):272-9. doi: 10.1055/s-0031-1298388. Epub 2012 Jun 22.
14. Arzi B, DuRaine GD, Lee CA, Huey DJ, Borjesson DL, Murphy BG, Hu JC, Baumgarth N, Athanasiou KA. Cartilage immunoprivilege depends on donor source and lesion location. Acta Biomater. 2015 May 28. pii: S1742-7061(15)00249-4. doi: 10.1016/j.actbio.2015.05.025. [Epub ahead of print]
15. Piedade SR, Pinaroli A, Servien E, Neyret P.KA outcomes after prior bone and soft tissue knee surgery. Knee Surg Sports Traumatol Arthrosc. 2012 Jul 25.
16. Gulihar A, Bryson DJ, Taylor GJ. Effect of Different Irrigation Fluids on Human Articular Cartilage: An In Vitro Study. Arthroscopy. 2012 Dec 19. pii: S0749-8063(12)01654-4. doi: 10.1016/j.arthro.2012.07.013. [Epub ahead of print]
17. Mah ET, Lee WK, Southwood RT, Carbone A, Leppard PJ. Effects of irrigation fluid on human menisci: an experimental comparison of water, normal saline, and glycine. Effects of irrigation fluid on human menisci: an experimental comparison of water, normal saline, and glycine. Arthroscopy. 1991;7(1):24-32.
18.Thein R, Haviv B, Kidron A, Bronak S. Intra-articular injection of hyaluronic acid following arthroscopic partial meniscectomy of the knee. Orthopedics. 2010 Oct 11;33(10):724. doi: 10.3928/01477447-20100826-11.
19. Gupta PK, Das AK, Chullikana A, Majumdar AS. Mesenchymal stem cells for cartilage repair in osteoarthritis.Stem Cell Res Ther. 2012 Jul 9;3(4):25. [Epub ahead of print]
20. Lee KB, Wang VT, Chan YH, Hui JH. A novel, minimally-invasive technique of cartilage repair in the human knee using arthroscopic microfracture and injections of mesenchymal stem cells and hyaluronic Acid-a prospective comparative study on safety and short-term efficacy. Ann Acad Med Singapore. 2012 Nov;41(11):511-7.
21 Gardner OF, Archer CW, Alini M, Stoddart MJ.Chondrogenesis of mesenchymal stem cells for cartilage tissue engineering. Histol Histopathol. 2013 Jan;28(1):23-42.
22. Hauser R, Phillips HJ, Maddela HS. The Case for Utilizing Prolotherapy as First-Line Treatment for Meniscal Pathology: A Retrospective Study Shows Prolotherapy is Effective in the Treatment of MRI-Documented Meniscal Tears and Degeneration. Journal of Prolotherapy. 2010;2(3):416-437.