Bone Substitutes

Recent Advances in Bone Grafting

1. Osteoconduction Factors

  • Osteoconduction: Ability of a material to serve as a scaffold for bone growth.

  • Characteristics of Autograft (Gold Standard):

    • Osteogenesis (new bone growth)

    • Osteoconductivity

    • Osteoinductivity

  • Limitations of Autograft:

    1. Donor site morbidity

    2. Limited supply

    3. Increased operating time, anesthesia requirements, and blood loss

2. Bone Graft Substitutes (BGS)

  • Ideal Characteristics of BGS:

    • Osteoinductive (OI)

    • Osteoconductive (OC)

    • Biocompatible

    • Bioresorbable

    • Structurally similar to bone

    • Easy to use

    • Cost-effective

3. Classification of Bone Graft Substitutes (Laurencin et al.)

  • Allograft-based:

    • Uses allograft bone alone or with other materials

    • Osteoconductive, less than osteoinductive

  • Cell-based:

    • Utilizes cells for tissue generation either alone or on a support matrix

  • Factor-based:

    • Natural and recombinant growth factors

  • Ceramic-based:

    • Calcium phosphate, bioactive glass

  • Polymer-based:

    • Either degradable or non-degradable polymers

4. Allograft-Based Substitutes

  • Common Use: Most frequently utilized bone substitute

  • Processing Method:

    • Fresh Frozen: Ensures OI + OC

      • Cancellous > Cortical due to BMP preservation, requires secondary sterilization

    • Freeze-Dried: Only OC

      • BMP depletion, loss of structural integrity, potential disease transmission.

  • Demineralized Bone Matrix (DBM):

    • Acid extraction of bone matrix, chemosterilized with Ag extraction

    • Collagenous and non-collagenous proteins remain; OC but lacks structural integrity.

    • Minimally osteoinductive due to BMP, TGF-B. Available as chips, gels, or pastes.

5. Cell-Based Substitutes

  • Commonly Used Source: Autologous bone marrow aspirate

  • Mesenchymal Stem Cells:

    • Potential to develop into osteoblasts, chondroblasts, or myoblasts based on the environment

  • Aspirate Site: Iliac crest

  • Centrifugation Process:

    • Produces 'huffy coat' containing progenitor cells with angiogenic and osteogenic cytokines.

    • Taken into a syringe for intraosseous injection.

6. Factor-Based Substitutes

  • Role of Growth Factors:

    • Regulate cellular activity, key examples include TGF-B, IGF-1 and II, PDGF, FGF, and BMP.

  • BMP Discovery: Marshall Urist (1965) identified BMP as osteogenic protein-7

7. Ceramic-Based Substitutes

Overview

  • Characteristics of Ceramics:

    • Inorganic, non-metallic solids created from heating mineral salts at high temperatures (>1000°C).

    • Hard and brittle; high compressive strength.

  • Bioceramics: Specifically designed for repairing and reconstructing diseased or damaged bone and joints.

Properties of Bioceramics

  • Bioinert:

    • Maintain properties in the host, resist corrosion and wear.

  • Bioactive:

    • Forms a strong bond with tissue; hydroxycarbonate apatite formation.

  • Bioresorbable:

    • Broken down by the body; slowly replaced by bone; stable phases depend on water, pH, and temperature.

Applications

  • Uses of Ceramics:

    1. Orthopedic load-bearing coatings

    2. Bone graft substitutes

    3. Bone cements

Advantages and Disadvantages

  • Advantages:

    • Biocompatible, wear resistant, lightweight, no disease transmission, less stress shielding.

  • Disadvantages:

    • Low tensile strength, low toughness, not resilient.

Applications in Clinical Use

  • Bioinert:

    • Hip arthroplasty, knee prosthesis, bone screws, implant coatings, load-bearing implants.

  • Bioactive:

    • Direct bonding with tissue, interfacial bonding strength exceeding cohesive strength.

  • Bioresorbable:

    • Chemically broken down by the body and degrade.

    • Slowly replaced by bone.

    • Chemical produced as the ceramic is resorbed, must be able to be processed through the body's metabolism.

    • Synthesized from synthetic chemicals or natural sources (e.g., coralline HA).

    • Available as pastes, putties, granules, etc.

    • Most widely used: Calcium phosphate (HA), occurring naturally in bones.

    • CaPO₄ stable phase depends on water, pH, and temperature.

    • Used in forms such as:

      • Cement

      • Coating on implants

      • Powders

    • Calcium sulfate:

      • Osteoconductive bone void filler for bone lesions.

      • Filling of cysts, bone cavities, and benign segmental defects.

      • Applications in spinal fusion.

      • Filling of bone graft harvest sites.