What Are Bone Substitutes?
Bone substitutes are substances that have been used to replace missing or defective bones for many centuries till now. Defects or missing bones can arise for various reasons, such as traumatic fractures, infections, surgery, tumor, or other congenital (present from birth) causes. There are various bone substitutes used. However, the most preferred bone replacement till now is the autologous bone graft.
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The other substitutes are allograft, xenograft, or other synthetic bone substitutes used in isolation or combined with other substances.
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The ideal properties of a bone substitute are osteoconductive (property by which the matrix stimulates the growth of bone tissues), osteoinductive (property that induces bone formation), biocompatibility, cost-effectiveness, structural similarity, and ease to use. This article will discuss the various bone substitutes used and their clinical applications.
Types of Bone Substitutes Used in Clinical Practice: Bone substitutes are broadly classified into two types based on their origin. There are biologically derived bone substitutes and synthetic-derived bone substitutes.
What Are Biologically Derived Bone Substitutes?
1. Demineralized Bone Matrix (DBM): This type of bone substitute is an allograft derived from human bone sources, which are acid treated, resulting in the loss of mineral components but retaining the organic matrix and growth factors. Growth factors are naturally occurring molecules capable of differentiation, proliferation, and wound healing. The growth factors retained in the DBM are insulin growth factor (IGF), fibroblast growth factor (FGF), Bone morphogenic protein (BMP), and transforming growth factor (TGF). A 93 percent DBM comprises a collagen matrix with five percent growth factors. Due to the presence of collagen, DBM shows osteoconductive and osteoinductive properties. However, their efficacy still needs to improve, and they are only used to fill and are not preferred as an isolated bone substitute. A combination of DBM and bone marrow aspirate has shown better results in spinal fusion surgeries.
2. Platelet-Rich Plasma (PRP): Platelets are essential to blood cells that play a significant role in clotting. This type of blood substitute is derived from the blood by the process known as centrifugation (a mechanical process used to separate components of a liquid) through gradient density. The primary component of platelet-rich plasma is fibrinogen, platelets, and other growth factors. Using PRP shows reduced infection rate and adverse effects; however, their efficacy to promote bone healing has not been proven and is only used in combination with other bone substitutes.
3. Bone Morphogenic Proteins: Bone morphogenic proteins (BMP) are one of the growth factors belonging to the transforming growth factor β family. They are unique because they can induce the migration of osteogenic progenitor cells to the site of bone formation. There are 20 types of BMP identified now. Genetic engineering uses recombinant gene technology in BMP-2 and BMP-7 to produce larger quantities of BMP and in their practical clinical application in non-union fracture healing and spinal fusion surgery cases. The utilization of BMP in various clinical settings has been constrained due to limitations such as the requirement for a molecular carrier for delivery and its elevated cost.
4. Hydroxyapatite (HA): Hydroxyapatite is a bioactive mineral component in teeth and bones. They are highly biocompatible and show structural similarities to targeted site bone. The porosity nature of hydroxyapatite allows osteoconductive properties and a low resorption rate, increasing the substitute's longevity in the implanted site. These properties of HA allow for the progression of slow-bone ingrowth. Natural and synthetic forms of HA are usually available in combination with composite materials and collagen. They are used in various orthopedic and traumatology surgeries as void bone fillers.
What Are Synthetic-Derived Bone Substitutes?
1. Calcium Sulfate: Calcium sulfate, or plaster of Paris, was initially used as a void filler for bone defects. They are osteoconductive, cost-effective, have structural similarities, and are available in different forms. However, they have an increased resorption rate, lack osteoinductive and osteogenic properties, and carry the risk of infection. Hence they are only used as a vehicle or carrier for growth factors or local antibiotic delivery.
2. Calcium Phosphate Cement: Calcium phosphate cement is produced by mixing calcium phosphate powder with a liquid, forming a workable paste that usually hardens within 15 to 80 minutes based on its formulation. Even though it has a longer resorption rate, they are generally avoided in clinical practice due to their increased brittleness and other adverse effects.
3. β-Tri-Calcium Phosphate (β-TCP): β-Tri-Calcium Phosphate has been used as one of the gold-standard bone substitutes for many years. They are highly biocompatible and bioresorbable materials. They comprise osteoconductive properties due to their increased porous nature, promoting bone remodeling. They have enhanced blood vessel capillarity that promotes the colonization of bone-forming cells at the implanted site and have the potential to influence blood vessel formation. However, the properties of β-tri-calcium phosphate could not match the mechanical properties of cancellous bone and allograft material, and they are only used selectively. In the surgical management of medial knee osteoarthritis (a type of arthritis causing degenerative changes in the joints of the bones), using preforms of β-TCP showed increased biocompatibility, 95 percent of osteointegration, and 98 percent of complete bone healing. Also, β-tri-calcium phosphate has been used in the management of long bone fractures like fractures of the proximal tibia bone for many years
4. Biphasic Calcium Phosphate: β-tri-Calcium Phosphate is often combined with Hydroxyapatite. The combination of HA and β-TCP (Biphasic Calcium Phosphate) showed improved mechanical properties and higher bone ingrowth. There are various forms of this substitute, and their compressive strength is between 150 to 200 MPa (megapascal) which is lower than the strength of cortical bone. Recent studies show the use of biphasic calcium phosphate in managing non-union fractures (fractures that show no sign of improvement even after six months of management) and hip arthroplasty.
Conclusion:
Various types of bone substitutes have been used in clinical practice for many years, and they have advantages and disadvantages. Hence, they are used selectively based on the location, bone defect, and the property of the bone substitute. Many procedures require bone substitutes like vertebroplasty, spinal fusion surgery, augmentation, filling voids, etc. Various research and studies are currently being conducted to improve the properties of bone substitutes.
