Bone Grafting and Bone Substitutes in Orthopedic Trauma: Materials, Techniques, and Clinical Applications

Въведение

The successful management of orthopedic trauma often hinges on achieving stable fracture fixation and promoting robust bone healing. While many fractures heal uneventfully with appropriate stabilization, certain clinical scenarios present significant challenges to bone regeneration. These include large bone defects resulting from high-energy trauma, nonunions where healing has failed, arthrodesis procedures requiring bony fusion, and fractures occurring in compromised host environments such as osteoporotic bone or infection. In these challenging situations, bone grafting and the use of bone substitutes become essential adjuncts to surgical fixation, providing the necessary biological stimulus or structural support to facilitate healing.

Bone grafting, the transplantation of bone tissue, has been a cornerstone of orthopedic surgery for over a century. Autologous bone graft, harvested from the patient’s own body (typically the iliac crest), remains the gold standard due to its inherent osteogenic (containing bone-forming cells), osteoinductive (containing growth factors that stimulate bone formation), and osteoconductive (providing a scaffold for bone growth) properties. However, autograft harvesting is associated with significant limitations, including donor site morbidity (pain, infection, nerve injury), limited available volume, and increased operative time.

These limitations have driven the development of alternative bone graft materials, collectively known as bone substitutes. These materials aim to replicate one or more of the key properties of autograft while avoiding its drawbacks. Allograft bone, derived from human cadaveric donors, offers osteoconductivity and some osteoinductivity but lacks viable osteogenic cells and carries a small risk of disease transmission. Synthetic bone substitutes, including ceramics (calcium phosphates, calcium sulfates), polymers, and composites, primarily provide osteoconductive scaffolds, sometimes augmented with osteoinductive factors. Growth factors, such as Bone Morphogenetic Proteins (BMPs), represent a powerful osteoinductive strategy, stimulating the patient’s own cells to form bone.

The selection of the appropriate bone graft material or substitute depends on a complex interplay of factors, including the specific clinical indication, the size and location of the defect, the mechanical environment, the host’s biological potential, and material properties. Understanding the characteristics, advantages, and limitations of each option is crucial for optimizing clinical outcomes in orthopedic trauma.

This comprehensive review explores the spectrum of bone grafting materials and bone substitutes used in orthopedic trauma, covering their biological properties, material characteristics, surgical techniques for application, clinical indications, evidence-based outcomes, and future directions in this rapidly evolving field.

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Biology of Bone Healing and Graft Incorporation

Fundamental Principles of Bone Regeneration

1. Phases of Fracture Healing:

   • Inflammatory Phase: Hematoma formation, inflammatory cell influx, cytokine release.
   • Repair Phase: Soft callus formation (fibrocartilage), hard callus formation (woven bone), angiogenesis.
   • Remodeling Phase: Conversion of woven bone to lamellar bone, restoration of original bone shape and strength (Wolff’s Law).

2. Key Biological Properties for Grafting:

   • Osteogenesis: Presence of viable bone-forming cells (osteoblasts and osteoprogenitor cells).
   • Osteoinduction: Presence of growth factors (e.g., BMPs, TGF-β) that recruit and stimulate host mesenchymal stem cells (MSCs) to differentiate into osteoblasts.
   • Osteoconduction: Provision of a scaffold or matrix that supports cell attachment, migration, proliferation, and new bone deposition.
   • Structural Support: Mechanical integrity to maintain space and withstand physiological loads during healing.

3. Cellular and Molecular Mechanisms:

   • Role of mesenchymal stem cells (MSCs) and osteoprogenitor cells.
   • Key signaling pathways (BMP/Smad, Wnt, FGF).
   • Importance of angiogenesis and vascular invasion.
   • Interaction between inflammatory cells and bone cells.
   • Mechanical signaling pathways influencing cell behavior.

Graft Incorporation Process

1. Initial Inflammatory Response:

   • Hematoma formation around the graft.
   • Influx of inflammatory cells.
   • Release of cytokines and growth factors.
   • Initiation of vascular ingrowth.

2. Osteoconduction Phase:

   • Host MSCs and osteoprogenitors migrate onto the graft surface.
   • Angiogenesis progresses into the graft material.
   • Cells attach, proliferate, and differentiate on the scaffold.
   • Deposition of new bone matrix onto the graft surface.

3. Osteoinduction Phase (if applicable):

   • Release of growth factors from the graft (autograft, some allografts, BMPs).
   • Recruitment and differentiation of host MSCs.
   • Stimulation of osteoblastic activity.
   • Amplification of the bone formation cascade.

4. Remodeling Phase:

   • Gradual resorption of the graft material (if resorbable).
   • Replacement of graft with host lamellar bone.
   • Integration of the graft into the host skeleton.
   • Restoration of mechanical strength.
   • Process influenced by mechanical loading.

Factors Influencing Graft Success

1. Host Factors:

   • Age and overall health.
   • Nutritional status (protein, calcium, vitamin D).
   • Comorbidities (diabetes, vascular disease, renal failure).
   • Smoking status.
   • Medications (NSAIDs, steroids, chemotherapy).
   • Local soft tissue condition and vascularity.
   • Presence of infection.

2. Graft Material Properties:

   • Osteogenic, osteoinductive, osteoconductive potential.
   • Porosity, pore size, and interconnectivity.
   • Surface chemistry and topography.
   • Mechanical strength and degradation rate.
   • Biocompatibility and immunogenicity.

3. Surgical Technique Factors:

   • Adequate debridement of nonviable tissue.
   • Preparation of the recipient site (e.g., decortication).
   • Stable fracture fixation providing appropriate mechanical environment.
   • Intimate contact between graft and host bone.
   • Adequate soft tissue coverage.
   • Avoidance of excessive heat during preparation.

Autologous Bone Graft

Properties and Advantages

1. Biological Properties:

   • Osteogenic: Contains viable osteoblasts and MSCs.
   • Osteoinductive: Contains endogenous growth factors (BMPs, TGF-β).
   • Osteoconductive: Provides a natural collagen/hydroxyapatite scaffold.
   • Non-immunogenic: Derived from the patient.

2. Предимства:

   • Considered the