Follow-Up Instructions After AniCell Amnion Therapy

AniCell Biotech has developed safe amnion-based technology including innovative biological membrane bandages, implantable (subcutaneous and intravenous), and topical forms of amnion that contribute to the diversity of AniCell’s product line which is designed to support the body’s innate healing capabilities in a variety of indications.  Cryopreserved cellular and reconstitutable acellular products impart the advantage of immediate availability for off-the-shelf use at the time of diagnosis, avoiding delays that result from processing or culturing that is required of other orthobiologic products before implantation.  Indications in which veterinarians have reported safety and positive outcomes with use include but are not limited to ligament and tendon injuries, osteochondrosis lesions, degenerative or infectious osteoarthritis, meniscal injuries, bone chips, and non-healing fractures, hoof-related conditions, wounds, ocular conditions, dental lesions, surgical wounds, wound infections, resistant infections, infectious diseases, autoimmune diseases, organ dysfunction (kidney, liver, gastrointestinal, and reproductive), metabolic (insulin resistance and other endocrine dysregulation), ischemic and inflammatory conditions.  Amnion helps support and protect diseased and injured tissue, serving primarily as a bioscaffold that provides building blocks such as extracellular matrix components (i.e. collagen, hyaluronic acid, proteoglycans, glycosaminoglycans, fibronectin, laminin, and others), bioacative signaling molecules (i.e. growth factors, cytokines, chemokines), and cellular components (i.e. stem cell components like exosomes), along with antimicrobial, anti-inflammatory/immunomodulating, anti-scarring, pro-circulatory, anti-apoptotic, and anti-microbial factors, that have been documented in human and veterinary science publications to communicate with the patient’s immune system to collectively modulate inflammation, fight infection, and recruit the patient’s stem cells where needed to help support healing and repair of injured or damaged tissues. 

Ocular & Wound Implant Care by Owner

Some ocular injuries require the application of an amnion disc that is placed on the corneal surface.  The eyelid is then sutured closed to keep the disc in place.  These sutures may be removed 5-10 days after placement by your veterinarian.  Other injuries may only necessitate placement of the ophthalmic disc without sutures plus eye drops, and others may only need eye drops.  Eye drops need to be stored in the refrigerator and the vial gently rotated prior to application.  By day 3, there may be some excessive tearing and/or yellow exudate which is the amnion being incorporated into the wound.   Discontinue the use of drops if excessive discomfort persists after application.  If there appears to be a reaction to the amnion disc, call your veterinarian immediately.

Wound care post-amnion membrane implantation requires simple bandage changes at days 10, 15, and 20, etc. until the wound is healed.  Your veterinarian may want to recheck the wound at any one of these bandage changes.  Depending on the size of the wound, it will be covered with a yellow exudate for up to 30 days post-application which is the breakdown and incorporation of the bioscaffold components into the wound as new tissue and is part of the dynamic allograft-supported repair, not purulent material indicating wound infection.  This must not be rinsed or scraped off.  Amnion has been reported in the literature to have strong antimicrobial properties that help protect the wound from infection.  Simply peel off the old telfa (non-stick dressing) and replace it with a new telfa, followed by a gauze wrap, and then a vet wrap.  You may want to take a photo to track the progress.  Additional therapies may be prescribed by your veterinarian such as antibiotics and/or pain control medications.

What should I expect after amnion therapy?

Immediately after amnion implantation for a wound/injury, the amnion begins to support healing, with veterinarians who use the product reporting anecdotally increased comfort (decreased swelling and soreness) levels that are observed within hours to days after implantation along with increased early voluntary mobility.  Ocular discs and/or eye drops have anecdotally demonstrated increased comfort and less squinting within 24-48 hours.  Conversely, owners have reported on occasion that their horse is lethargic and lacks an appetite for 24 hours which typically subsides quickly. 

Rehabilitation Expectations

In cases where AniCell has been used on an acute injury, we recommend 24-48 hours of stall rest and shorthand walks before embarking on a protected, controlled, accelerated, and aggressive rehabilitation program as prescribed by your veterinarian.  This is to avoid overexertion or exuberant play in which your horse may cause further injury.  Rehabilitation protocols involving any of the orthobiologic implants are essential and typically more aggressive with advancement and return to work faster than what owners have experienced with past injuries.  The targeted forces and motion produced by physical therapy are converted into mechanical signals, helping the cells direct proper healing and alignment of the tissues to restore optimal structure, strength, and function to the injured tissues much like what the fetal tissues experienced in normal growth and development.  Client compliance is critical to the most successful outcomes.  Initial exercise involves hand-walking to avoid overexertion or exuberant play where they can reinjure themselves.  Your veterinarian will require recheck examinations which are important in determining the rate at which rehabilitation should progress and if indicated, other therapies such as shockwave may be recommended to further enhance healing.  It is important to check with your veterinarian regarding all rehabilitation modalities (i.e. therapeutic ultrasound, low-level laser, pulsed electromagnetic therapy, etc., because they may be synergistic or may impede amnion-based therapy.)  The science behind, the timing, frequency, and interactions of these therapies has not been completely studied and determined at this time.  Above all, it is important to remember that your horse’s rehabilitation should progress at a tolerable level without inducing increased stiffness, pain, or lameness during or after exercise.  If any of these signs occur, contact your veterinarian, return to the prior level until soreness has resolved, and work up more slowly.

Possible Side Effects

In a small percentage of cases, there have been reports of injection site swelling, mild soreness, and/or lameness which may appear  4-24 hours post-implantation and last 2 days to 2 weeks but is self-limiting and does not require intervention.  This may be because amnion does NOT suppress the natural inflammatory response necessary for healing.  Inadvertent implantation of amniotic material into the fascia or deeper connective tissues, including tendons, ligaments, or joint spaces, can also result in increased inflammation and soreness.  These reactions are not harmful or permanent, do not impair healing, and in some cases may be necessary for healing.  In these cases, we recommend low-impact exercise such as swimming (if not a back problem) or brisk hand-walking for 15-20 minutes 2-3 x/day to further mobilize the material. If the horse is unable to exercise, the owner may perform range-of-motion exercises and stretching of the area for 5–10-minute sessions 3-5x/day to help mobilize the amnion.  If necessary, the area may be hot-packed for 10-20 minutes 2-3 times per day and a DMSO sweat applied to reduce inflammation without wrapping.  The best measure to counteract the discomfort is to exercise or mobilize the area to further distribute the amnion.  If discomfort persists after 48 hours, consult your veterinarian to see if a short course of appropriate temporary pain management or antihistamine is advised.   Anti-inflammatories should be discontinued for 6 weeks post-implantation.  If pain relief is necessary, using gabapentin or an opioid analgesic (i.e. butorphanol, tramadol, or buprenorphine) is recommended instead of NSAIDS such as bute, banamine, or Equioxx (firocoxib), or any type of corticosteroid (including joint injections), (after the single NSAID dose given with amnion implantation to help prevent minor reactions and post-implantation soreness) as these medications compete and interfere with the healing effects of amnion.  Avoid vaccination of your horse for 2-3 weeks pre- and post-implantation if possible. 

When should I expect to see results?

• Veterinarians using the product report that approximately 25% of cases will experience almost immediate impact from therapy in the first 2-3 weeks with continued improvement for the following weeks/months.
• Veterinarians using the product report that approximately 40% will steadily improve over the course of 6 weeks.
• Veterinarians using the product report that approximately 25% will not see any substantial response for 4 weeks and then experience considerable improvement over weeks 5 and 6.
• Veterinarians using the product report that less than 10% will not see any substantial improvement warranting re-implantation with the same or different amnion product or a different course of treatment. If your horse or pony has multiple issues causing inflammatory signaling outside of the intended area that was implanted, the amnion may have gone to support healing in those areas of higher inflammatory signaling first. 
• According to the scientific literature available regarding amnion-based technology, you should expect consistent improvement in the quality of tissue healing and function as well as a reduction of healing time by ½ and a 5x decrease in reinjury rate improved over current standard of care and adult regenerative therapy (i.e. PRP, adult bone marrow stem cells, adipose stem cells) recovery time and reinjury rate.

Do I need to retreat my horse?

While reports from veterinarians typically suggest improvement by 6 weeks after amnion therapy, some cases have reported slow and progressive outcomes over 6 months.  While these cases are not typical, every equine will respond differently depending on their age, health status, and co-morbidities.  Most injuries addressed with amnion products require only a singular implantation unless there are special circumstances involved such as wounds larger than 10x10cm, exposed bone, severe or resistant wound infections, or animals with metabolic/endocrine disease (i.e. pituitary pars intermedia dysfunction, insulin resistance, or equine metabolic syndrome).  These animals are typically still good candidates for EquusCell™ products but may require a secondary application.  Chronic and progressive disease conditions such as renal failure, pituitary pars intermedia dysfunction, hyopthroidism, insulin resistance, exercise-induced pulmonary hemorrhage, osteoarthritis, and others, often require some element of periodic implantation of EquusCell™ products.   Animals with these conditions may require additional implantations starting at 30 days, using the same technique until the condition is resolved.  There is no claim that amnion abates the disease but supports improved health of the tissue through remodeling of that tissue with the amnion bioscaffold.  With tendon injuries in racehorses, veterinarians using the product report that a second implantation of EquusCell™ near the tendon when the horse goes back to full training and racing increases the chance of a positive outcome.