PAST, CURRENT AND FUTURE INTERVENTIONAL ORTHOBIOLOGICS TECHNIQUES AND HOW THEY RELATE TO REGENERATIVE REHABILITATION
Interventional orthobiologic techniques should be appropriately coupled with the correct rehabilitation protocols that facilitate the bodies natural healing mechanisms. This, via corrective function following on from orthobiologic injections. The regenerative rehabilitation should be associated with mechanotherapy. Mechanotherapy refers to the therapeutic properties by which body movements provide mechanical stimuli to remodel cells. This field examines mechanobiology, transduction and adaptation to effectively direct tissue modeling and remodeling.
Physical rehabilitation therapy is a pivotal part of the regenerative orthobiologics treatment. The aim of all regenerative therapy is to facilitate healing through targeted specific tissue adaptations (through appropriate exercise and joint mobilisation) in order to promote balance and to prevent future injuries.
Understanding interventional orthobiologic treatments and how tissue responds to the correct rehabilitation will help guide the development of appropriate protocols for each type of common regenerative procedures. The purpose of this article is to provide a history of orthobiologics and describe the role of corrective rehabilitation after these interventional procedures. This will enable a better understand certain conditions requiring regenerative interventions and to and how these treatment should be coupled with rehabilitation for optimal healing and return to function.
The healing of musculoskeletal tissue
The healing cascade of damaged tissue works in 3 phases:
1) inflammation
2) proliferation
3) maturation
Inflammation is the start of the healing cascade from injury. This is characterised by initial bleeding from injury and then constriction of blood vessels which activates coagulation and clot formation with platelets. This clot works as the scaffold for other healing cells such as Pro inflammatory cells and growth factors to invade and start the inflammatory-healing-repair cascade.
Growth factors modulate healing and the inflammatory phase. The inflammatory phase then brings in cells which clean the area. Following this, angiogenesis (the development of new blood vessels) occurs to enhance blood flow to the injured area. Next, fibroblasts come in and begin to lay down collagen tissue.
Maturation and remodeling is the phase between approximately day 8 and one year composed of strengthening local tissue and stimulating you collagen networks. The largest difference between regenerative rehabilitation and post-surgical rehabilitation is not only to get the patient back to normal activity, but also to change the predisposing biomechanical factors that contributed to the injury in the first place.
There are many different types of connective tissues which make up the musculoskeletal system - including muscles, tendons, ligaments, cartilage and bone. Each of these tissues is unique with regard to function and composition, and there are slight alterations to the healing processes.
Muscles
The main function of muscle is to generate contractions to facilitate motion and provide stability. In muscle injury or a micro tear, this triggers the local clot formation. Inflammatory cells migrate to the injured site at the same time as new muscle cells being stimulated. Following on from this, the remodeling phase begins, ultimately into new muscle fibers.
The ability of skeletal muscle to respond to different trauma such as exercise, immobilisation, direct trauma, or chemical relies on the natural regenerative capacities. We also understand that muscle loading through exercise increases vascularity and the number of muscle cell recruitment which collectively enhances skeletal muscle regeneration. In addition, it is understood that regenerated muscles, respond to injury better. Therefore, movement is crucial to preserve the new cell recruitment in order to improve skeletal muscle rehabilitation.
Tendons
Tendons are tough connective tissue that connect muscle and bone and have been demonstrated to have a specific structure. Tendon damage and injury is a very common complaint and occurs due to a number of different reasons. The process of tendon remodeling involves collagen synthesis that begins immediately after exercise. There are various different factors within tendon inflammation, however, it is unclear how exactly overloading inhibits adaptive remodelling activity leading to the degeneration. We understand that exercise strengthens tendons, but chronic cases of inflammation can sometimes inhibit this. This is where many regenerative orthobiologic treatments have been targeted to manage various upper and lower extremity tendon injuries (tendinopathies).
Ligaments
Ligaments function to link bones with other bones, in order to stabilise a joint. Traumatic ligamentous injury can result in either a partial or complete tear and can proceed through the typical three phases of healing described above.
Cartilage
The joint cartilage deals with huge amounts of forces and allows for smooth gliding motion without friction. The absence of blood supply is what limits the healing capabilities. Joint cartilage gets its nutrition from joint synovial fluid which protects and nourishes.
Bone
Bone also proceeds through the same healing cascade of inflammation and remodeling. New cartilage cells (chrondrocytes) initially form a soft callus then new bone cells (osteoblasts) gradually replace soft callus with immature bone.
Review Of Regenerative Orthobiologic Treatments
Because each tissue type in the body has differences and similarities in healing, regenerative orthobiologic treatments have been developed that are specific to each tissue type. Ultimately, regenerative orthobiologic treatments are assigned with the goal of reducing pain, promoting and facilitating tissue repair and optimal function.
The first and most popular regenerative orthobiologic is known as platelet rich plasma which is the use of concentrated autologous blood that has been separated into its most enriching growth factor components as further described below.
Platelet Rich Plasma
Platelet rich plasma (PRP) consists of higher concentration of platelets from whole blood it is separated into components and concentrated to be more potent than is physiologically possible. The goal of the use of PRP is to have a high therapeutic platelet concentration in a small volume of plasma in order to stimulate and facilitate a healing potential in tissue that otherwise has a poor healing capacity or is at a disadvantage chronically. PRP therapy initially gained popularity in oral and cardiac surgery in the 80's. The mechanism behind PRP is to enhance the healing cascade in a controlled fashion due to a higher concentration of platelets and growth factors being injected than are normally physiologically present. The platelets play a central role in the new tissue stimulation and healing by releasing growth factors stored in them.
The presence or absence of leukocytes in PRP is important. Leukocytes are essential mediators of the inflammatory response, that assist the immuno-defence protection against infectious agents, and contribute to wound healing. It is important to note that red blood cells are eliminated from the PRP preparation as the iron contained in them release cytotoxic oxygen free radicals which can be destructive. Of note, application of PRP in individuals on non-steroidal anti-inflammatory drugs (NSAIDs) is not recommended as NSAIDs inhibit platelet function and may have a diminished therapeutic effect.
Based on the literature for knee osteoarthritis Leucocyte PRP has been shown in numerous studies to stimulate cartilage and has been found to have pain relieving benefits. it is very important that during the PRP preparation that all of the red blood cells are eliminated. The majority of white blood cells are maintained to facilitate healing. The The previous consensus was with maintaining leukocytes is that that type of PRP can be harmful to healing tissues and increase the inflammatory response. However, leukocytes generally maintained lymphocytes which have been shown to be present with stem cells and thus a higher percentage increases stem cells. Leukocyte rich PRP was shown to decrease inflammatory production and promote tissue regeneration in tendons. High amounts of literature also indicates success of pain reduction and function of PRP treatment for plantar fasciitis. This also done in association with comparison to steroid, with PRP showing better efficiency long-term.
Clinical Evidence
Tendinopathy
PRP for elbow tendinopathy has demonstrated efficacy in treating chronic tendinitis when compared to steroids with long-term follow-ups. Examination of the results of treatment of Achilles and patellar tendinopathy (knee) has demonstrated that PRP injections improved function and pain with good functional outcomes for about four years post-injection. Many studies of shoulder tendinitis (rotator cuff tendinopathy) have been performed with platelet rich plasma and platelet rich fibrin injections done intraoperatively with good clinical outcomes. PRP fibrin which improved repair integrity for large rotator cuff tears without an associated greater improvement in function and had lower re-tear rates for small to large tears at one year. Optimization of ingredients for tendinopathy concluded that higher platelet counts with leukocytes and a slightly acidic pH injected may be ideal to facilitate the healing of tendinopathies that have failed other conservative management.
Osteoarthritis
Osteoarthritis is characterised by cartilage loss within a joint space, due to various different factors, and is related to an insufficiency in healing of cartilage, leading to progressive degeneration. Currently, high amounts of literature exists which demonstrates that joint PRP injections are efficacious in treatment of knee osteoarthritis in terms of pain relief and functional improvement at 3, 6, and 12 months follow-up, this also in comparison with other injectables like ozone and corticosteroid.
In order to decrease pain in osteoarthritis and promote repair, off-loading the region of cartilage that is subjected to the highest force is important to prevent further degeneration. It is important to note that treatments offered to date cannot regrow cartilage, however, they can improve the healing environment to stimulate repaired, improve pain, and function.
Sciatica - Lumbar Radiculopathy
Low back pain with radiculopathy (pain/sensation going down the leg) that doesn’t respond to normal conservative treatment is treated most commonly with an epidural steroid injection which is the most commonly performed pain management procedure. However, steroid can often be short lived and have side-effects. These side effects has led to the trial of regenerative treatments within spinal pain. Clinical evidence for PRP in the literature are mostly limited to treatment disc injury/damage and facet joint inflammation. Bhatia performed a pilot study of PRP for the treatment of radiculopathy and reported good improvement in pain reduction that was sustained for over three months.
Is PRP treatment permanent?
In cases of arthritis, PRP works to attempt to improve the environment and to reduce inflammation. It is important to note that when using orthobiologics to treat tendons or ligaments the theory is that this intervention is more of a semi-permanent solution as it is assisting in repairing the tendon. With that said, many tendons can be stubborn and ligaments may require combined treatments prior to deeming them as “healed”.
The next regenerative orthobiologic is prolotherapy.
Prolotherapy
Prolotherapy is a treatment that uses a dextrose solution for promoting local healing of chronically injured tissue through stimulating both inflammatory and noninflammatory pathways. However, it is not used that frequently these days. It was initially found that repeated injections was associated with increases in collagen and this increased stabilisation.
Clinical Research
Treatment of hand osteoarthritis - prolotherapy has shown benefits in pain and hand movement in comparison to steroid and local anaesthetic.
Neck (spine) – improvements have been shown in reduced pain and increased stability.
Knee osteoarthritis - a systematic review and meta-analysis in 2016 which identified clinically relevant improvements of function and pain when compared to formal home therapy exercise alone and the benefits were sustained for one year.
Spinal pain and sacroiliac joint pain
Kim et al published a randomised controlled trial noting that sacroiliac joint prolotherapy injections were found to be superior to steroid injections. Hoffman et al noted that prolotherapy may be a satisfactory option for SI joint instability. Solmaz et al concluded that prolotherapy injections may be a viable option prior to considering reoperation in failed back surgery syndrome.
Chronic tendinitis (tendinopathy)
Rabago et al and Scarpone et al published 2 trials that demonstrated effectiveness of prolotherapy in tennis elbow (lateral epicondylitis) where participants showed improved grip strength compared to. Treatment of shoulder tendinitis (rotator cuff) - 59% of the prolotherapy participants reported a change in pain score with comparison to 37% who received saline.
Stem Cells – This is going to be covered in a different article.
REHABILITATION WITHIN REGENERATIVE MEDICINE
Research on rehabilitation protocols for regenerative procedures is lacking. No standard protocols exist for rehabilitation following regenerative therapies, it is all pretty much based on clinical opinion. It is appreciated that controlled gradual return to activity is the best course of action, with restricted exercise in the initial acute phases of tendon and ligament healing.
McKay et al recently published proposed regenerative rehabilitation guidelines and proposed protocols for the treatment of knee osteoarthritis. It is suggested that moderate physical exercise is beneficial for knee osteoarthritis and can slow the progression of degradation by providing some cartilage protection. A common issue in patients with knee osteoarthritis is weakness of the supporting muscles along with ligamentous instability and inactivity as a result. Muscle strengthening and stabilisation exercises are beneficial. A combination exercises looking to promote functional mobility, strength, and stability is recommended in post treatment rehabilitation due to the role rehabilitation plays in cartilage sell stimulation and role in improving function after regenerative orthobiologics treatment.
General rehabilitation guidelines exist for PRP and stem cell therapy which involve four phases of rehabilitation therapy. See descriptions below.
A suggested rehabilitation protocol following platelet-rich plasma for treatment of tendons is slightly different to the osteoarthritis model described above. This protocol has three phases See descriptions of the phases below.
Currently, there is no consensus on rehabilitation after PRP injections but as described above, the notion of gradually increasing the load and activity as tolerated can facilitate healing and repair, along with gauging the intensity of workouts based on pain level to keep it at a minimum of 2/10 to avoid further soft tissue injury.
CONCLUSIONS
Prolotherapy has been shown to have good success at kick starting the inflammatory cascade to promote healing. However, here at Dynamic Regenerative Medicine we prefer more natural biological treatments like PRP. Prolotherapy is used in the treatment for mild joint instability. PRP is an effective treatment for chronic tendon injury (tendinopathy). PRP is also very effective for mild to moderate cases of joint arthritis by providing haling growth factors. Although more aggressive surgeries may be warranted in refractory or severe cases where orthobiologics did not help; having an orthobiologic option combined with targeted rehabilitation protocols would be optimal prior to moving onto surgery.
The goal of regenerative rehabilitation is to restore a patient back to the level of function prior to the injection, but also to restore the biomechanical influences that contributed to the injury by focusing on the joint or injured area as a part of a whole. The goal of interventional orthobiologics is to heal damaged to tissue and to rectify the corrective function of the surrounding structure in order to optimise full function as a whole.
We want to try and move musculoskeletal practice, orthopaedics and sports medicine away from the current emphasis on pain management, the use of NSAIDs, steroid injections and rest, towards stimulating repair, progressive movement, combined with functional strengthening and damage prevention. A combined rehabilitative approach to improving biomechanics along with utilising regenerative injections to induce healing and promote stability may assist in keeping joints, ligaments, tendons and muscles healthy and stronger as we age or prevent future injury in the younger population.
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