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Researchers and doctors are still trying to improve the biology of healing. Nowadays, surgeons have perfected strong repairs and, in many cases, have reached the limit of what can be done to heal a joint mechanically. Enter biological healing. After injury and surgery, there is a layer of scar tissue on top of the healthy tissue; this scar tissue isn’t the same as it was before the injury. So, researchers and doctors are trying to find ways to revert this scarred tissue back to its original, healthy state. And they still have a long way to go.

Orthobiologics are substances found in our bodies that may stimulate the healing of injured tissues, such as tendons, muscles, and possibly cartilage. The idea is that adding extra healthy tissue to an injury will restart and improve the healing process.

Common orthobiologics include:

  • Grafts or scaffolds, which help treat fractures or augment bone fusions.
  • Platelet rich plasma, or PRP, which is harvested from the patient’s own blood and injected into the site of injury. Typicall used in two ways: 1) to treat tendinopathies and tendon tears and 2) articular pathologies (cartialge).
    • If you’re doing a tendinopathy use PRP with white blood celsl fo rinflamatory
    • If youre doing articualr pathologes, use hydraol acid.
  • Medicinal signalling cells, which are taken from a patient’s bone marrow or fat and placed on the site of injury. They are commonly (but incorrectly) referred to as stem cell treatments.

Some orthobiologics, such as amniotic fluid, can be taken from another person’s body. Despite some false claims to the contrary, these tissues do not contain live cells. Furthermore, the safety and effectiveness of these substances are controversial.

Dr. Romeo sends to PCP who use ultrasound to ensure it goes in the right way. Used for lateral epicondylitis (tennis elbow), rotator cuff tendonitis, strains to latissimus and teres major. Intrarticaulr injection for elbow and shoulder. —GEt patient in room, draw 60 to 90 CC, centrifuge the blood, and then inject under ultrasound. Takes 30 mins to set that patient up.

“Other than using bone graft materials for fracture healing or to augment a bone fusion, the most used orthobiologics substance is platelet rich plasma.”

The goal of orthobiologics

In some cases, orthobiologics can actually regenerate certain cells and tissues, such as blood and bone, to function as they did before the injury or disease.

Other tissues, such as tendons, cartilage, and ligaments, can be treated by orthobiologics, but cannot be truly regenerated at this time. The primary value of orthobiologic treatments for these tissues is to relieve symptoms by reducing or eliminating inflammation. Orthobiologics may have long-term benefits as they promote the development of healing tissue or (scar tissue) that helps prevent the inflammation from returning

Orthobiologics cannot work miracles. Some false claims exist, stating that cartilage can be regrown in arthritic joints or that torn tendons can be healed with their pre-injury state. These claims are not currently supported by high-quality scientific studies.

However, orthobiologics are always evolving, and perhaps one day we will be able to develop therapies that fully regenerate injured tissues both in appearance and function.

Want to learn more? In this 2017 video, Dr. Romeo discusses the evidence for and against using platelet rich plasma and [medicinal signalling cells] to treat rotator cuff tears.

Platelet rich plasma (PRP)

Platelet rich plasma comes from the patient’s own blood. To get PRP, a sample of the patient’s blood is taken and a doctor spins it down using a machine called a centrifuge. The layer of plasma that is full of platelets is removed and re-injected into the site of the injury.

Platelet rich plasma contains growth factors—chemicals that stimulate the body’s own healing cells to come to the injury site, which can improve the healing process.

Notes from Dr Hrubes video, Rothman Orthopedics intro to orthobiolgics 2022 https://www.youtube.com/watch?v=DqTphC1eV9o&t=347

  • Patient’s own blood is collected and centrifuged. PRP is extracted and injected into the injured area. (autologous transfer)
  • It increases growth factors to an area, which promotes temporary relief and reduces inflammation.
  • In a way, it re-starts the healing process for an injury. (vascular GF, epithelial GF, etc). SO, new blood flow to an area is an indication that it’s working
  • PRP injection is anti-inflammatory
  • Different types of PRPs have different uses
    • Leukocyte-poor, platelet-rich plasma
    • Leukocyte-rich, platelet-rich plasma
    • Platelet-poor types
  • Best uses:
    • High quality evidence: Tendon stuff
      • Partial UCL tears
      • Lateral epicondylopathy
      • Glut med tendinopathy
      • Plantar fasciitis
      • Knee OA (mild-mod)
    • Moderate evidence
      • Patellar tendinopathy
      • Achilles tendinopathy
  • Best fits:
    • Tendons: LR PRP or LP PRP
    • Cartilage: LP PRP
    • Muscles: LP platelet-poor plasma, for chronic injuries
  • Limits:
    • Timeline (slow)
    • Expensive
  • Advantages
    • Can be done in clinic
    • Can be individualized and tailored (dose, PRP vs PPP, LR vs LP)

Notes from Dr Romeo Video 2017

  • A lot of interest, PRP contains GFs to stimulate cells to come to the site of healing
  • The
  • Small improvement re-tear rate for small to medium tendon tears when treated with PRP
  • Using PRP in surgery: If PRP is a solid matrix and can be held close by, there is a better outcome; also its better if you can keep it between the tendon and the bone.
  • But the evidence is not compelling enough for insurers to cover; we cannot say the standard of care is an orthobiologic. It has been in use for 10 years but it has failed to really improve tendon healing for the most part. So, we’ve moved on. So what about cells?

Experts are debating whether PRP can be used to treat acute (new) injuries of the tendons, ligaments, and muscles. Many high-performance athletes in the NFL, NBA, MLB, NHL, and MLS have been proponents of receiving PRP injections for a variety of conditions early in their treatment programs. With it, they hope to accelerate healing and avoid more severe injury or surgery. PRP for acute injuries is still an investigational treatment. It is available and recommended to high-level athletes, competitive recreational athletes, some work-related athletic injuries, and those patients who want innovative treatments that have not yet been scientifically proven.

The most promising use of PRP is to treat tendon injuries, ligament injuries, and the symptoms of cartilage loss or arthritis. PRP is often used in chronic (older or ongoing) injuries. Overall, however, there are likely to be more promising treatments than PRP.

Risks and benefits

Possible benefits of PRP can include:

  • Improved symptoms
  • Regained function
  • Reduced or eliminated need for more intensive treatments, such as surgery or long-term medication

PRP is less invasive than other orthobiologics and it can be done in a clinic. Also, the type and dose of PRP can be tailored to the individual’s needs.

From all the research to date, however, the success of PRP seems modest. Fortunately, the risks associated with this form of therapy are minimal. Patients may experience increased pain at the injection site, but the risk of other problems such as infection, nerve injuries, and tissue damage does not appear to be increased. The main disadvantages of PRP seem to be that it is expensive and that the outcomes can be minimal.

Results

PRP has shown minor success in some studies of hamstring injuries; rotator cuff tears; ligament injuries of the knee, ankle, or elbow; and sprains of some joints.

Despite these studies, insurance companies have remained firm that the evidence is not strong enough for the treatments to be covered by medical insurance.

Dr. Romeo believes that in the right patient and for the right condition, PRP may help heal the damaged area, relieve symptoms, and delay or eliminate the need for surgery. While PRP is offered as an evidence-based treatment option, the patient is financially responsible for the treatment.

Pluripotent cells (stem cells)

MANY GROUPS ADVISE AGAINST THE USE OF THE WORD “STEM CELL”

From Dr Hrubes talk: https://www.youtube.com/watch?v=DqTphC1eV9o&t=347

  • Cellular repair mechanisms include: Fat-harvested stem cells are called MFAT (microfragmented adipose tissue, athletes need to have enough fat) and Bone marrow concentrate (BMC)
  • In the US, limited manipulation of stem cells is allowed. IE in the USA, not allowed to apply hormones or growth factors. You are not allowed to remove it from the physical premises. This is an FDA guideline.
  • Repopulates stem and progenitor cell pools on cartilage. This signals the body to bring more stem and progenitor cells.
  • This doesn’t fix arthritis forever, but can slow it down
  • BMC/BMA:
    • Non union
    • RC partial tears
    • Knee OA
    • Femoral head AVN
  • MFAT
    • Knee OA
    • Achilles defect
    • Meniscus tear
    • GH joint wi
    • GH OA and tendinopathy
  • Limitations
    • More invasive procedure
    • Bone marrow MSCs (mesenchymal stem cells) decrease with age
  • Are these stem cells?
    • She tries not to use the word stem cells
    • A researcher originally coined the term “mesenchymal stem cells” because researchers thought they were injecting stem cells. But this isn’t really what we’re doing. The person who coined the term regrets this nomenclature. In the lab, they are truly pluripotent, but in the body, they are not. → Many scientists/doctors are now calling them medicinal signalling cells. (this keeps the MSC label)
    • NOONE in the USA is truly injecting stem cells.
    • Mesenchymal stem cells is a misnomer - its time to change the name
  • Common myths busted:
    • Orthobiologic injections DO NOT contain stem cells
      • Umbilical cord injections do not contain any live cells
    • No type of orthobiologic/regenerative medicine is better than any other
    • We CANNOT regrow cartilage
    • Sometimes multiple injections are required. We won’t know if one will be enough.
    • Recovery time ranges from weeks to months. It’s common to get worse for the first few weeks — this is the healing process re-starting.
    • The nomenclature “regenerative medicine” is pretty misleading. Mayo clinic suggests “restorative medicine”
    • This is not a quick fix
    • There are no standards yet

What happened with Dr Romeo’s mirror study of 2014 Hernigou?

(The below paragraphs are from Dr Romeo’s video above)

[Dr Romeo feels a lot in orthobiologics is more hype than science.] Unfortunately, [this treatment] has been widely mislabeled as “stem cell treatment.” There are hundreds of centers across the US that offer “stem cell treatments” at a high price. They falsely claim their treatments can treat a variety of conditions by regenerating or regrowing new tendon and cartilage.

In truth, [medicinal signalling cells] are not reattaching tendon to bone (regrowing Sharpey’s fibers) after a tear. They are not growing new hyaline cartilage in an arthritic joint. They are not regenerating tendon or muscle. One thing they CAN do is reduce inflammation and pain. However, the science for this process is inexact and researchers still don’t completely understand how it works.

Harvesting medicinal signalling cells is also more complicated than just drawing blood. Some physicians in Dr. Romeo’s practice are experts at providing this nonsurgical treatment. Dr. Romeo will refer you to one of his non-surgeon partners who will give more details and let you decide if medicinal signalling cells treatment is right for you.

Risks and benefits

Medicinal signalling cells harvested from the bone marrow, fat, or bursas, may provide a better and longer healing response for certain conditions. They help bring new cells to injured tissues, they help form new extracellular matrix, and they can increase the development of blood vessels near an injury.

Results

Many test tube (in vitro) studies have suggested tremendous promise with medicinal signalling cells. However, in general, human studies have not been overwhelmingly positive to the point that insurance companies and government health insurance are willing to pay for this treatment.

Scaffolds/grafts

Another promising orthobiologic is scaffolds or grafts. Dr. Romeo uses scaffolds in more complicated surgical cases, such as repeat or revision tendon surgeries.

Risks and benefits

From Dr Romeo’s video https://vimeo.com/427773916 2017

  • Since this video, the Rotium Interpositional Graft for RCR was approved
  • Think there is a new way forward with “Scaffolding”. So many single tendon tears re-tear after surgery
  • Combines making holes in bones to create bleeding, adding PRP/growth factors, adding strong tapes. Need to add something else that will help tendon re-integrate back to the bone (grow roots into bone). Something that is missing is called a nanofiber scaffold. (They used in this case, an acellular, sterile, dermal allograft)
  • Nanofiber scaffold - thin, white material, gets placed between tendon and bone (make a sandwich lol). In the past, dermal allograft was used to enhance strength, not to provide any biological healing activity

Current clinical trial: Rotator Cuff Healing Using a Nanofiber Scaffold in Patients Greater Than 55 Years

  • Nanofiber Solutions ( Atreon Orthopedics )

Trial: Rotator cuff repair using a bioresorbable nanofiber interposition scaffold: a biomechanical and histologic analysis in sheep

  • “Bioresorbable scaffold”
  • Scaffolds are bioabsorbable materials that function as a temporary structure that acts to preserve physiological and/or biologically active molecules owing to its architecture and physicochemical properties encouraging restoration or regeneration of native tissues. Recently, the electrospinning of bioabsorbable synthetic polymers has allowed the creation of microporous structures with fiber diameters within the nanometer range (referred to as “nanofiber scaffolds”). These nanofiber scaffolds have been shown to encourage the development of normal tendon-bone enthesis architectures demonstrated through their ability to support cellular migration, infiltration, and proliferation.47,59 The augmented healing response is further supported by the gradual degradation of the scaffold such that it can be replaced with new tissue as the healing process proceeds toward completion.2,20
  • In other words, a scaffold is made out of materials that can be naturally integrated into the body’s tissues. There are chemicals in the nanofibre scaffold that are the same as the ones found in the human body, and these encourage tissue healing and growth. These scaffold materials contain tiny “nanofibres” that can help stitch the injured tendon back down onto the bone. The scaffold gradually breaks down and is resorbed by the body and replaced by natural tissues.
  • Results: Most important, this study demonstrated no evidence of an abnormal or pathologic tissue response to the scaffold, along with an improved enthesis architecture and biomechanical properties over the control group. Following the investigation in order of results, biomechanical testing demonstrated statistically significant improvements in ultimate load to failure for both the 6-week group and the 12-week group in the scaffold-treated group. In fact, by 12 weeks, the ultimate load to failure was approaching 75% of the nonsurgical tendon strength, demonstrating not only overall strength benefits but also an accelerated healing response within the scaffold-augmented shoulders. Furthermore, the variance in the results was less with the scaffold than without a scaffold, and all tendons healed despite the fact that the sheep were allowed to re-establish their normal pattern of weight bearing and walking immediately following their recovery from the surgical procedure.
  • In sum, the results showed no abnormal healing found; improved strength at 6 and 12 weeks; accelerated healing. This study was done in sheep.

Trial: Comparison of glenohumeral contact pressures and contact areas after glenoid reconstruction with latarjet or distal tibial osteochondral allografts

  • The principal findings of this study demonstrated that glenoid bone reconstruction with distal tibial allografts resulted in significantly higher glenohumeral contact areas than reconstruction with Latarjet bone blocks at 60° of abduction and at the ABER position. (CADAVERIC STUDY)

Study: Augmentation of Tendon Graft–Bone Tunnel Interface Healing by Use of Bioactive Platelet-Rich Fibrin Scaffolds

  • Platelet-rich fibre scaffolds that contained cytokines
  • Used to help healing interface between bone and tendon

Study: A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair (2015)

  • They tried to develop a more robust material (scaffoled) that could withstand the procedure of surgical implantation (prior scaffolds had been too delicate)
  • “Nanofibre-mediated bioactivity”

Results

Scaffolds can be particularly valuable in rotator cuff surgery. Many rotator cuff surgeries fail—in other words, the chance of the tendon healing properly to the bone in revision surgery can be below 50%. Many rotator cuffs also retear after surgery. This indicates that they likely never healed properly after surgery. Tendons seem to heal and regain strength incredibly slowly. Scaffolds can help with ________. Also, with cartilage defects, scaffolds may play an important role.

For more information about orthobiologics related to the treatment of shoulder, elbow, or sports medicine conditions, please request an appointment with experienced Chicago orthopaedic surgeon Dr. Anthony Romeo. Call or email our office today to schedule your visit. Please remember that most of these treatments are not covered by insurance and that payment is the responsibility of the patient.

  • American Shoulder and Elbow Surgeons
  • American Orthopaedic Association
  • Arthroscopy Association of North America
  • American Medical Association
  • SECEC-ESSSE
  • New England Shoulder and Elbow Society
  • American Orthopaedic Society for Sports Medicine
  • American Academy of Orthopaedic Surgeons