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Ortho-Biologics & Regenerative Medicine in Orthopaedics

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The term Ortho-Biologics is used to represent all forms of treatments that involve the use of various substances obtained from patients themselves. These substances may include cells, tissues, growth factors or components of the blood. Ortho-biologic substances are used to stimulate tissue healing and allow faster recovery.

 

Ortho-Biologic substances are taken from the patient and then concentrated or filtered to obtain a small quantity, for injection into the sites of injury. The growth factors, contained within or secreted by these substances, promote new tissue growth, enhance tissue healing, reduce pain, reduce inflammation, and help in restoring musculoskeletal function. This technique not only helps in the healing of the injured / damaged tissue, but also helps to preserve it.

 

Ortho-Biologics are also known as Regenerative Cellular Therapies. They are rapidly expanding the treatment options for arthritis and chronic tendon injuries and muscle tears.

Ortho-biologics treatments include Platelet Rich Plasma (PRP), Bone Marrow Aspirate Concentrate (BMAC), Autologous Chondrocytes Implantation, Autologous Osteoblast Implantation & Stem Cell therapy.

 

Autologous Conditioned Plasma (ACP) & Platelet rich plasma (PRP) 

Platelets are small, colourless, disk-shaped cell fragments lacking a nucleus that are found in blood and play an imperative role in clot formation. They also have antimicrobial properties that support healing, infection control and the release of growth factors. These growth factors orchestrate the key biological processes required for healing like angiogenesis, inflammation resolution and tissue regeneration.

 

Platelet-rich plasma is also known as platelet-enriched plasma, platelet-rich concentrate and autogenous platelet gel. The normal platelet count in whole blood in a healthy individual is between 150000-45000 per microliter. To be labelled as platelet rich plasma, the platelets should be of 4-5 times of the baseline.

 

Platelet-rich plasma is an autologous suspension of platelets that is prepared from patient’s own blood via double centrifugation technique. This can be done as an OPD procedure with all due sterility precautions.

 

This rich concentrate contains several powerful and key growth factors like platelet-derived growth factor, transforming growth factor, platelet factor 4, interleukin-1, platelet-derived angiogenesis factor, epidermal growth factor, platelet-derived endothelial growth factor, epithelial cell growth factor insulin-like growth and vascular endothelial growth factor. These special factors stimulate tissue healing and also stimulate and signal local stem cells.

 

Platelet rich plasma has been used in diverse musculoskeletal conditions like lateral epicondylitis (tennis elbow), rotator cuff tears, subacromial impingement, shoulder osteoarthritis, patellar tendinosis, osteoarthritis of the knee, Achilles tendon tears, plantar fasciitis, non-union of bones and topically to control bleeding after knee arthroplasty.

 

PRP is the most studied of the OrthoBiologics therapies. Many, but not all, of these studies have shown benefit in reducing pain and improving function in patients with arthritis or chronic tendinopathies.

 

PRP & ACP are similar but PRP has 10 times higher concentration of healing factors.

 

In order to get maximum benefit after PRP injection, doctors avoid prescribing anti-inflammatory medications, which can reduce the effectiveness of this treatment.

 

Bone Marrow Aspirate Concentrate (BMAC)

Autologous (patient’s own) bone marrow contains stem and progenitor cells, which under the right conditions will divide and form precursor cells that have the capacity to generate new tissues. This includes blood, bone, cartilage, fat and blood vessels. These cells are necessary to maintain the health of the tissues over time, and to respond to injury.

 

Bone marrow is aspirated with a needle from the hip or pelvis. The majority of cells in bone marrow are blood-forming cells. However, a small number of cells in bone marrow are referred to as ‘connective tissue progenitors’ (CTPs). CTPs can make bone, cartilage, fat and other fibrous tissues that are important for joint function.

 

 

CTPs and other cells in bone marrow can be concentrated by several methods and then injected into sites of diseased or damaged tissue. When injected, CTPs may contribute to new tissue formation. They may also release proteins known as growth factors or cytokines. These growth factors may also act on cells that are already in the diseased or damaged tissue to improve their function.

The method of aspiration is most often done in tandem with a surgical procedure in the operating room with all sterile precautions. 

 

Autologous Chondrocyte Implantation (ACI)

Specialised cells called chondrocytes are arthroscopically harvested from a healthy joint cartilage. These chondrocytes are then cultured, and their numbers multiplied in a specialised lab over a period of 4 to 6 weeks. These cells are then implanted into cartilage defects via arthroscopy or open surgery either mixed with a fibrin gel or preloaded /seeded onto a scaffold that is used to fill up the cartilage defects. These defects get healed and covered with new cartilage by 3 months.

 

Autologous Osteoblast Implantation

This involves harvesting the bone marrow cells from the iliac crest region of the pelvis. These cells are isolated and cultured to multiply their numbers in a specialised lab over 4 to 6 weeks. These osteoblast cells are then implanted into bone defect areas. Osteoblasts form new bone at implanted areas and the bone defects are healed by 3 months. This therapy is used in cases of Avascular necrosis (AVN) of femoral head at the hip joint, at sites of fracture non-unions and bony defects of any origin.

 

 

Stem cells

Adult mesenchymal stem cells are also considered Ortho-Biologics.

 

A stem cell has the capacity to differentiate into multiple types of cell and is able to self-renew. Stem cells are able to keep up the stem cell pool and produce daughter cells which can differentiate into specialized tissues forming cartilage, tendon and bone cells. Stem cells are present in mesenchymal tissues like bone marrow, fat, synovial membrane, periosteum and others.

 

Bone marrow is common source of these stem cells and the iliac crest is the most preferred site for harvesting stem cells.

 

There are two ways of providing stem cells to the injury site.

 

In first method, aspirated bone is directly inserted to the injury site. This eliminates the time it would take for the stem cells to reach the injury on their own and also delivers them in a higher concentration, which speeds the healing process.

 

In other method, bone marrow is aspirated, and the stem cells are separated and cultured in laboratory media to increase their numbers before being used 4 to 6 weeks later.

 

Stem cells have been used with encouraging results in treatment of non-unions, osteonecrosis (Avascular necrosis - AVN) of femoral head, spinal fusion and for filling of bone defects. But routine use of stem cells cannot be recommended due to lack of enough studies.

 

Visco-supplementation

This involves injecting the knee joint with special liquids (hyaluronic acid) that increase the viscosity of the joint fluid and improve the health of the knee cartilage. This leads to improved joint lubrication and reduced friction between the arthritic surfaces of the knee joint.

 

These specialised injections are part of regenerative medicine. These get manufactured either synthetically or from animal sources. The properties of these injections are made to closely match the viscosity of naturally occurring joint synovial fluid. Based on their viscosity these injections can be a single dose or multiple dose therapy. Based on the joint selected for injection, the volume of such injections can be anything between 2 cc to 6cc.

 

Minor cartilage lesions are thought to heal with such injections. Their pain-relieving effect lasts for 6 months to 12 months. Ideally most useful for early stages (mild to moderate) knee arthritis in young patients.

The conditions commonly treated with Ortho-Biologics are:

 

Osteo-arthritis – commonly used for knee, shoulder or ankle arthritis in mild to moderate stages. This may include Hyaluronic acid injections, PRP injections or BMAC injections.

 

Tendinitis – Rotator cuff lesions, Tennis Elbow, Golfer’s Elbow, Wrist De Quervain’s tenosynovitis, Quadriceps or Patellar tendinitis, Achilles tendinitis or Plantar Fasciitis. PRP injections are most commonly used for these problems.

 

Ligament injuries – around knee, shoulder, elbow and ankle

 

Femoral head Avascular Necrosis (AVN) - can be treated with PRP or BMAC or cultured Osteoblastic cells

 

Chronic muscle injuries (e.g. Gastrocnemius and soleus muscle tears)

 

Chondral injuries (injuries involving the articular cartilage overlying all joints)

 

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