Novel Approaches to Equine Joint Health

Michael Caruso III, VMD, Dipl. ACVS-LA

Reedsdale Equine Specialists
Tullahoma, TN

Orthobiologics and regenerative medicine are terms used somewhat interchangeably. Clinician opinion,
based on the appropriate regenerative treatment chosen, varies greatly. However, the basics of
evaluation and diagnosing lameness and performance injuries in the horse remain crucial to a successful
outcome regardless of treatment option. Most regenerative options, and the decision to choose one,
originate from a performance or lameness concern. The examiner must be certain to perform a
thorough physical examination and lameness evaluation. Discussed below briefly include platelet-rich
plasma (PRP), autologous protein solution (Pro-Stride®), mesenchymal stem cells (MSCs), equine
amniotic allograft (RenoVo®), alpha-2 macroglobulin (α2M), and polyacrylamide hydrogels (PAAG;
Noltrex Vet®, Arthramid Vet®).

PRP is a blood-derived therapy known to contain and release many important factors such as platelet-
derived growth factor (PDGF), transforming growth factor beta (TGF-beta), insulin-like growth factor
(IGF-1), and vascular endothelial growth factor (VEGF), among others. These substances play key roles in
repair mainly through effects on cellular proliferation, cell migration, and the synthesis of collagen. PRP
is used to stimulate healing of tendon/ligament demopathies, in non-septic arthritis, cartilage
degradation/tears, and has been used and studied in wound healing. PRP is widely administered intra-
articularly with positive results both in human and veterinary medicine. Singla et al. (2017) compared
steroid versus PRP in human chronic lower back pain/sacroiliac joint disease. In this study, PRP injections
were more effective than steroid injections for sacroiliac joint pain with 90% of patients after PRP
experiencing significant pain relief compared to only 25% of patients after the steroid injection. Injecting
PRP into the sacroiliac joint ligaments led to significant improvement in pain scores (Ko 2017; Singla et al
2017). This author routinely uses PRP for intralesional soft tissue desmopathies and intra-articularly for
the treatment of osteoarthritis as well as in arthroscopic surgery aftercare.

Autologous protein solution (Pro-Stride®) is a product that combines PRP and IRAP (interleukin-1
receptor antagonist protein) into one injection. Studied by Bertone et al. (2014), this product promotes
“normal” healing of cartilage and intra-articular structures. It features the combination of effects
produced by PRP and IRAP. It is a blood-derived product that undergoes similar preparation and
processing as PRP but differs in that it requires a two-step centrifugation process with two separate
centrifugation tubes specific to the product to isolate the IRAP and PRP portions from the blood sample.
It is best used for the treatment of osteoarthritis in horses. In this author’s opinion, its efficacy is
greatest when used younger horses or horses within the early stages of the arthritic process.

Mesenchymal Stem Cells (MSCs) can be harvested from bone marrow, fat (adipose), joint fluid, and
umbilical samples (among others). For this discussion, bone marrow-derived MSCs are described.
Although stem cells do have pluripotency, this is not believed to be the benefit of their actions to
improve healing. Like PRP, their effect on the local environment (immunomodulatory) at the site of
injury and the potential recruitment of beneficial cytokines and growth factors is believed to be their
mode of action. MSC therapy may provide a “better” repair through improved fiber alignment, more
organized collagen, and less scarring (Godwin et al. 2012). Following intra-articular administration of
MSCs after stifle arthroscopy for meniscal injury, Ferris et al. (2014) found a 75% return to athletic
function in the treatment group versus 60-63% with surgery alone. MSCs are used for the treatment of
tendon/ligament desmopathies, cartilage defects, meniscal injuries (intra-articular), laminitis, and
wound healing. This author occasionally uses MSCs for intra-articular administration and mainly in the
stifle joint with concurrent intra-articular soft tissue damage.

Equine amniotic allograft (RenoVo®) uses amnion to create a material that can be injected into a soft
tissue defect, used topically on healing wounds, and injected into joints. Equine amnion is known to
contain many different types of collagen (I, III, IV, V, and VII), tissue inhibitors of metalloproteinases,
laminin, fibronectin, proteoglycans, and hyaluronic acid (Fowler et al. 2019). This product’s aim is to
improve the efficiency and quality of healing. This author does not use this product intra-articularly.

Alpha-2 macroglobulin (α2M) is a device that was originally used for disc-related back pain in human
medicine. Alpha-2 macroglobulin is an acute phase protein that is primarily produced by the liver but is
also produced in smaller amounts by the articular cartilage, synoviocytes, and macrophages. It’s
mechanism of action is via gene regulation, non-specific protease inhibition, and cytokine and growth
factor modulation. This is also a blood-derived protein found in the plasma. It allows one blood draw
that produces multiple doses that can be frozen and administered later per the attending veterinarian’s
protocol. This device is typically administered in the joint but can be administered into soft tissue
defects. This author has used this product with mixed results.

Polyacrylamide hydrogels (PAAG) are extremely viscous, stable, large, biocompatible molecules that
have good tissue integration. They have viscoelastic properties that attempt to replicate the normal
properties of healthy synovial fluid. To this author’s knowledge, there are only two PAAGs currently
available on the equine market (Noltrex Vet®, Arthramid Vet®). Christensen et al. (2016) showed that
the hydrogel incorporates into the synovium at approximately 4 weeks post-injection, but prior to
incorporation, it lines the synovium. PAAG causes synoviocyte hyperplasia and hypertrophy,
angiogenesis, and collagen deposition in the surrounding tissues. The hydrogel tissue integration has a
stabilizing effect on the synovium and joint capsule with a consequent increase in tensile strength and
elasticity (Tnibar et al. 2017). There is still speculation regarding the mechanism of action. One
perspective details that the PAAG causes a decreased exposure to pro-inflammatory cytokines via
covering the inflamed synovium. Another proposed mechanism of action details that hydrogel tissue
integration produces a reduction in nociceptor and mechanoreceptor activation of neural pathways.
This is believed to reduce joint hypersensitivity, a common feature of osteoarthritis. These products
were originally marketed and recommended for use in severe or chronic osteoarthritic joints refractory
to other treatments. But this treatment option, for many veterinarians including this author, is now
evolving as the primary or first-line joint therapy utilized in arthritic joints. This veterinarian routinely
uses PAAGs in acute and chronic joints with good results.
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