Ross Hauser, MD; Danielle Matias, PA-C; Demi Foster, APRN

When discussing non-surgical applications of regenerative medicine, such as bone marrow-derived stem cell therapy, Platelet-rich Plasma therapy, or Prolotherapy, discussions must be tempered with the realistic indications and outcomes that may be expected from these treatments.

• These regenerative medicine injections cannot regrow an ACL from nothing. If there is a complete disintegration of the ligament, it cannot be regrown. The goal of these treatments is to help with a partial tear or overstretched ACLs. These treatments can restore strength and function to this type of ACL damage in many patients.
• Further, these treatments are designed to strengthen the entire knee capsule. All the ligaments should be treated to help the partially stretched or torn ACL heal, or if ACL reconstruction or more ACL reconstruction surgeries are declined by the patient, strengthening the knee capsule may help prevent knee instability and more rapid degenerative arthritis from developing.

What is Prolotherapy, and where is the research? Please visit our Prolotherapy research page for extensive and detailed information.

Prolotherapy is a “new” old treatment that has been utilized in clinical practices for over 80 years. Standardized and reviewed in clinical application by Dr. George Hackett in the 1950s, Prolotherapy has been shown to be an effective treatment in patients who suffer from joint instability due to ligament damage and overuse, and related musculoskeletal and osteoarthritis. Prolotherapy’s popularity as a treatment for chronic pain has intensified over the past two decades among both physicians and patients, as clinical and anecdotal observations have proved in many cases its effectiveness as a non-surgical option for joint and back pain.

• Prolotherapy is a nonsurgical regenerative injection technique that introduces small amounts of an irritant solution to the site of painful and degenerated tendon insertions (entheses), joints, ligaments, and in adjacent joint spaces during several treatment sessions to promote the growth of normal cells and tissues.

Irritant solutions most often contain dextrose (d-glucose), a natural form of glucose normally found in the body.

In January 2017, doctors writing in the Orthopedic Journal of Sports Medicine wrote of the controversies surrounding the repair of partial ACL tears. One of the controversies was reconstructive surgery. In this study, the researchers found that biologically augmented ACL-repair techniques (PRP and stem cells) improve healing and outcomes of both the native ACL (non-surgery) and the reconstructed graft tissue (surgery). (1)

In 2003, K. Dean Reeves, MD, published in the journal Alternative Therapies in Health and Medicine (2) these findings:

• 16 knees with machine-measured ACL laxity were injected bimonthly with 10-25% dextrose solution (Prolotherapy) for 1 year and then an average of 4 times yearly thereafter until 3-year follow-up.
• Summary: Using simple dextrose injection into 16 knees with a loose ACL ligament,
  • 10/16 knees were no longer loose by machine measurement at the time of follow-up, and symptoms had improved.
  • A symptom of osteoarthritis improved even in those who still tested loose.
  • At the 3-year follow-up, pain with walking had improved by 43%, subjective swelling improved by 63%, flexion range of motion improved by 10.5 degrees, and machine-measured ACL ligament looseness improved by 71%.

PRP injections or ACL Surgery in older patients?

An August 2022 study in the European Journal of Translational Myology (3), a publication dedicated to the study of joints and muscles, writes: “In old patients with ACL rupture, surgery is not recommended due to the person’s low level of activity and knee osteoarthritis. Platelet-rich plasma (PRP) is a good treatment option in inflammatory cases in orthopedics. Hence, the aim of this study was to assess and comparison of the effect of PRP and arthroscopic surgery on anterior cruciate ligament rupture.

• 100 patients were randomly divided into two groups.
  • The first group of patients underwent ACL tendon repair surgery by arthroscopy and tendon graft.
  • The second group was treated by PRP injection.
  • Both groups of patients were visited from 3 months to 14 months after surgery or PRP treatments.
• Patients in both groups had significantly decreased pain severity after 14 months, but the patients in the surgical treatment group had significantly lower pain and a higher Range of motion compared to the PRP group.

Stem Cell Therapy involves direct bone marrow aspiration (or also concentrated) to get the stem cells to the site of the injury. We use bone marrow stem cells in conjunction with other Prolotherapy solutions to treat large articular defects in the meniscus areas. Typically, patients are seen every two months. Most patients need 3-6 visits. The good news is that during the time of healing, the patient can exercise and start getting back into great shape.

Doctors at the Department of Trauma Surgery and Sports Injuries, University Hospital of Salzburg, wrote in the Archives of Orthopaedic and Trauma Surgery:

“The ACL has the potential to heal upon intensive non-surgical rehabilitation procedures. Several biological factors influence this healing process as local intraligamentous cytokines (messengers that call for more inflammation (healing)) and mainly cell repair mechanisms controlled by stem cells or progenitor (creator) cells. Understanding the mechanisms of this regeneration process and the cells involved may pave the way for novel, less invasive, and biology-based strategies for ACL repair.”(4)

In 2015, doctors in China excitedly published research in the Chinese Journal of Reparative and Reconstructive Surgery, which said: “Enormous progress has been made in tissue-engineered ligament for repair and regeneration of ACL. With the development of biochemistry and scaffold materials, the tissue-engineered ligament will be used in clinics in the near future.”(5)

This research suggests that one day, doctors will be able to grow a new ACL in the laboratory and implant it into a knee. That is fantastic news for the people of the future, but what about today? Is there a way today to non-surgically repair a damaged ACL? Do you even need to replace the ACL?

Another team of Chinese researchers writing in the medical journal International Orthopaedics noted that the ACL has certain self-healing abilities after acute injury. These self-healing abilities have to do with stem cells (for a detailed discussion on how stem cells work, please see my article on stem cell therapy). The Chinese team suggested that leaving behind part of the ruptured ACL remnant would release native stem cells into the new graft and augment healing. In addition, taking stem cells from the remnant ACL may be a potential source of seeding cells for ligament regeneration. (6)

This research found agreement in the work of Korean doctors who wrote in the medical journal Current Stem Cell Research and Therapy about recent developments in mesenchymal stem cell (MSC)-based approaches for enhancing healing after ACL injuries. They suggest that stem cells are a promising treatment option for enhancing the biological healing of ACL grafts and restoring the functional properties to the levels of the native ACL, and ultimately improving clinical outcomes. (7)

What this research suggests is stem cell augmentation for the ACL graft to prevent ACL complications.

References

1 Dallo I, Chahla J, Mitchell JJ, Pascual-Garrido C, Feagin JA, LaPrade RF. Biologic Approaches for the Treatment of Partial Tears of the Anterior Cruciate Ligament: A Current Concepts Review. Orthopaedic Journal of Sports Medicine. 2017 Jan 25;5(1):2325967116681724.[Google Scholar]
2 Reeves KD Hassanein K Long term effects of dextrose prolotherapy for anterior cruciate ligament laxity: A prospective and consecutive patient study. Alt Ther Hlth Med May-Jun 2003, 9(3): p58-62.[Google Scholar]
3 Eslami S, Fattah S, Taher SA, Rezasoltani Z. Platelet-rich plasma therapy or arthroscopic surgery on repair of anterior cruciate ligament rupture. Eur J Transl Myol. 2022 Aug 1. doi: 10.4081/ejtm.2022.10538. Epub ahead of print. PMID: 35916761.
4 Hirzinger C, Tauber M, Korntner S, Quirchmayr M, Bauer HC, Traweger A, Tempfer H. ACL injuries and stem cell therapy. Archives of orthopaedic and trauma surgery. 2014 Nov 1;134(11):1573-8. [Google Scholar]
5 Sun Z, Li J. Research progress of tissue engineered ligaments Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2015 Sep;29(9):1160-6. Chinese. [Google Scholar]
6 Fu W, Li Q, Tang X, Chen G, Zhang C, Li J. Mesenchymal stem cells reside in anterior cruciate ligament remnants in situ. Int Orthop. 2015 Jul 31. [Google Scholar]
7 Jang KM, Lim HC, Bae JH. Curr Stem Cell Res Ther. 2015;10(6):535-47. Mesenchymal Stem Cells for Enhancing Biologic Healing after Anterior Cruciate Ligament Injuries. [Google Scholar]