Article By: Saisreeram Kandula and Rahul Saraf
Design by : Bhavya Jain and Jasneet Kalra
The term Orthobiologics refers to the use of biological substances naturally found in the body to help musculoskeletal injuries heal quicker. When they are used in concentrations many times the normal, they can potentially help speed up the healing processes.
Certain factors are essential in the process of healing. These factors include a good blood supply, extracellular matrix, stem cells and growth factors.
Stem cells
Inhere several unique characteristics that distinguish them from other cell types. They are unspecialized cells, which have the ability to differentiate into different adult cell types. There are two types of stem cells: embryonic stem cells which are truly pluripotent, and multipotent adult stem cells. A variety of multipotent adult stem cells exists in assumedly all tissues of the organism. They are responsible for maintaining the integrity of the tissue they reside in.
Mesenchymal stem cells (MSCs) are considered to be an orthobiologic substance. They can be isolated from a number of mesenchymal tissues like bone marrow, fat, synovial membrane, periosteum and others. These MSCs can be used for repair of various musculoskeletal tissues.
i. Tendon repair
Tendons are precariously supplied by blood vessels, hence injuries to the Musculo-tendinous areas are notorious for inadequate healing and chronicity.
Mesenchymal Stem Cells need to be introduced into the site of injury. This can be done through either scaffold application, or by direct injection of suspension of MSCs onto bone surface before tendon-bone refixation. Application of MSC in tendon repair shows promising results in animal models but requires further clinical data.
ii. Cartilage
MSCs can be recruited from subchondral bone by drilling, abrasion and microfracturing subchondral bone. This can stimulate formation of new cartilage.
iii. Bone
Current treatment strategies for bone repair include autologous bone grafts from the iliac crest, autologous fibula graft transfer and allogenic bone graft transplantation. However, these techniques show limitations, as bone supply is limited, autologous bone harvesting is accompanied with high rates of morbidity and allogenic transplantation inheres the risk of transmission of diseases or rejection
Recent in vitro trials found out that MSCs strongly promote angiogenesis by paracrine factors after mechanical stimulation, as occurring during fracture healing, which makes MSC more interesting for bone regeneration. Autologous mesenchymal stem cells were successfully implanted in a number of patients to enhance fracture/osteotomy healing, fill bone defects, treat pseudarthrosis, bone cysts, osteonecrosis, or enhance spinal fusion.
Growth factors
Platelet Rich Plasma (PRP) is a source of blood derived growth factors. Platelets are formed from megakaryocytes in the bone marrow. They contain granules namely α, δ and λ. They contain more than 30 proteins including platelet-derived growth factor (PDGF), transforming growth factor (TGF-β, β1 and β2 isomers), platelet factor 4 (PF4), interleukin-1 (IL-1), platelet-derived angiogenesis factor (PDAF), VEGF, epidermal growth factor (EGF), platelet-derived endothelial growth factor (PDEGF), epithelial cell growth factor (ECGF), insulin-like growth factor (IGF) etc. These proteins attract stem cells to the site of injury where they are developed into cells of repair, they induce proliferation of multiple cells as well as aid in angiogenesis.
PRP is treated with calcium chloride and thrombin, which forms a gel-like substance for direct application.
PRP has been used in treatment of musculoskeletal conditions like lateral epicondylar tendinopathy, rotator cuff tears, shoulder osteoarthritis, osteoarthritis of the knee, tendo- achilles tears, ACL reconstruction, non-union of bones and topically to control bleeding after knee arthroplasty.
PRP appears to be one of the most attractive option available in ortho-biologics due to its minimal side effects ; the relative ease of preparation, cost effectiveness and the ability to complete the procedure as a day care procedure. However, PRP preparation needs to be carried out in a sterile environment, preferably in bio-safety cabinets and the usage needs to be standardized
Matrix
This is the conductive material through which various cells interact to bring about healing of tissues. For example, in the case of a fracture of a bone, the gap between the two ends of the bone may be filled with a matrix material to hasten fracture repair.
Bone grafts, bone substitutes and bioactive factors can be introduced as matrix materials to foster bone healing through a variety of osteoconductive, osteoinductive and osteogenic mechanisms.
Osteoconductive property of a bone graft allows passive ingrowth of mesenchymal cells, blood capillaries and perivascular tissues into the graft.
Osteoinductive property of a bone graft is the property by which host mesenchymal stem cells are recruited with the help of various growth factors in order to differentiate into osteoblasts and chondroblasts. This in turn will help in formation of new bone.
Osteogenic property is the property that promotes new bone formation from the cells derived from the graft. only fresh autologous grafts and bone marrow transplants are typically involved in this process.
The following table compares these properties of various commonly used bone graft/ bone substitutes.
| Osteoconductive | Osteoinductive | Osteogenic | |
|---|---|---|---|
| Autograft | |||
| Cancellous | +++ | +++ | +++ |
| Cortical | + | + | + |
| Vascularize bone | ++ | + | ++ |
| Bone marrow aspirate | +/- | ++ | +++ |
| Platelet-rich plasma | – | +++ | – |
| Allograft | |||
| Cancellous | + | +/-b | – |
| Cortical | + | +/-d | – |
| DBM | + | ++ | – |
| Synthetic ceramics | |||
| Calcium sulfate | + | – | – |
| Calcium phosphate | + | – | – |
| Tricalcium phosphate | + | – | – |
Conclusion
Orthobiologics are the future for orthopedic and musculoskeletal medicine. As Orthobiologics get more advanced it is likely that more invasive, larger orthopedic surgeries can be prevented by Orthobiologic injections. Orthobiologics have the ability to heal areas of tissue damage without the risks, complications, and downtime associated with traditional orthopedic surgery.
Reference Bone grafts, bone substitutes and orthobiologics - PMC (nih.gov) Application of Stem Cells in Orthopedics - PMC (nih.gov) Orthobiologics and platelet rich plasma - PMC (nih.gov)