Orthobiologics: Therapeutic Agents for Musculoskeletal Healing

Introduction

With the immense growth in medicine, the most interesting and exciting innovation over the past few years is ortho-biologics. They come under regenerative medicine, which uses platelet-rich plasma and other therapeutic agents to treat and avoid surgical management of various musculoskeletal conditions. They have been studied, researched, and are effectively used in sports medicine and orthopedics to treat various sports-related injuries. The article discusses orthobiologics and its therapeutic agents in detail.

What Are Ortho-Biologics?

Orthobiologics includes many therapeutic agents and techniques that can improve symptoms and potentially increase the chances of healing the tissues such as bone, cartilage, tendons, muscles, ligaments, and meniscus. The substances currently used in ortho-biologics are bone grafts, platelet-rich plasma, stem cells, blood, and conditioned serum obtained from the same individual. They are minimally invasive, alternative treatment options to surgical management, or used as an additional treatment option when conservative treatment options fail to improve.

What Are the Therapeutic Agents Used in Ortho-Biologics?

Bone Grafts

• Bone grafting is the gold standard treatment option in patients with bone fractures, especially in cases with the fracture non-union, which involves fractures with no healing or failure in the union of the bones even after an adequate recovery period.

• There are various types of bone grafts, such as autologous, allografts, synthetic variants, etc.

• The properties of the bone graft required for osseous healing include the following.

  • Osteoinductive Properties: Properties of a graft that induces bone formation by employing osteogenic cells at the injury site.

  • Osteoconductive Properties: This property of the bone graft involves the process by which the matrix stimulates the growth of bone cells on its surface.

  • Osteogenic Properties: This bone graft property involves bone formation by the donor cells derived from the same individuals or from bone graft donors.

• An autologous graft involves deriving the graft material from one anatomic site and implanting it into another anatomic location of the same individual. They are the most preferred grafting method, which achieves maximum tissue compatibility comprising all three properties of bone graft. The commonly used types of autologous grafts include:

  • Cancellous bone graft: It is the most commonly used autologous bone graft with an increased osteogenic potential due to its higher concentration of osteocytes and osteoblasts (bone cells).

  • Cortical bone graft: This type of bone graft has increased mechanical strength and structural integrity but has limited concentrations of osteogenic bone cells. This results in a lack of osteogenic and osteoinductive properties of the graft.

  • Vascularized bone graft: These types of grafts are categorized as free grafts or pedicled grafts. Free grafts involve the removal of the bone from the donor site, implanting it in the affected area, and surgically connecting it to the adjacent blood vessel. A pedicled graft maintains the blood supply while transferring the donor bone graft into the affected area.

• Synthetic variants of bone grafts are introduced to stimulate the properties of bone grafts. These include:

  • Calcium sulfate.

  • Calcium phosphate.

  • Tricalcium phosphate.

  • Coral hydroxyapatite.

Platelet-Rich Plasma (PRP)

• Platelets are one of the blood cells essential for blood clotting. Higher concentrations of one’s plasma platelets above the normal range have provided effective results in orthopedic conditions.

• They are derived from whole blood by double centrifugation to remove red blood cells.

• They comprise different growth factors such as platelet-derived growth factor (PDGF), platelet factor 4 (PF4), transforming growth factor, platelet-derived angiogenesis factor, epithelial cell growth factor (ECGF), and insulin-like growth factor (IGF).

• These factors are essential for healing and speeding up the repair process. The properties of PRP are based on the release of these growth factors.

• They are used as a therapeutic agent in musculoskeletal injuries, especially tendon injuries like lateral epicondylar tendinopathy, rotator cuff injuries, Achilles tendinopathy, and patellar tendinopathy.

• Recent studies have shown the effectiveness of platelet-rich plasma in treating knee osteoarthritis over other interventions such as steroids and hyaluronic acid. They are effective in slowing down the disease progression in patients with early stages of osteoarthritis.

Stem Cells

• Stem cells are biological cells that can increase, heal and differentiate into other cells and regenerate tissues.

• They are easily obtained and isolated from bone marrow, adipose tissue (fat), and skeletal muscle. They are also obtained from the periosteum, blood, amniotic fluid, dental pulp, synovial tissue, and skin.

• They are released directly over the injured site during surgical management or through local injection with a suitable carrier.

• They work by releasing essential growth factors and cytokines necessary for developing new blood vessels, cell growth, and proliferation.

• They are effective in ligament-tendon injuries, osteoarthritis-cartilage defects, bone-joint injuries such as non-union fractures, spinal injuries, and fracture bone defects.

• They are extensively used in bone tissue engineering by combining them with suitable carriers to speed and improve the healing of tissues.

Vascular Endothelial Growth Factors

• Vascular endothelial growth factor (VEGF) is an essential growth factor that plays a vital role in stimulating the process of vasculogenesis (formation of new blood vessels) and in the embryonic development of the circulatory system.

• Bones are a vascularized organ that requires adequate blood supply for bone formation. Hence modulations in the levels of VEGF tend to improve bone repair and regeneration.

Parathyroid Hormone

• Parathyroid hormones (PTH) secreted by the parathyroid glands located in the neck are well known to regulate calcium homeostasis in the body and their influence on the activation of osteoblasts.

• They can mobilize progenitor cells from the bone marrow into the bloodstream.

• Various literature shows that the low-dose, intermittent administration of parathyroid hormone effectively stimulates bone repair. It has been shown to improve bone mineral density and strength; hence, daily administration of PTH is effective in the treatment of osteoporosis.

Conclusion

Orthobiologics, especially mesenchymal stem cells, platelet-rich plasma proteins, and bone grafts, show promising results in improving bone repair and healing and in relieving pain in various injuries involving ligaments, cartilage, tendon, muscles, and meniscus. However, the effectiveness of these agents is still being researched and studied. Various researchers exploring the indications and applications of ortho-biologics are underway and, in the future, hope to find a more significant role of orthobiologics in different treatments.