Biomedical Engineering: Bone and Fracture Healing

Bone and Wolff’s Law

  • Wolff’s Law Overview

    • Postulated by Julius Wolff in the 1890s

    • Bone adapts its structure to support physiological loads.

    • Also describes how bone remodels following fractures back to original shape and strength.

    • Source: Dr. Edmund Chao, Johns Hopkins University

Understanding Bone Adaptation and Remodeling

  • Mathematical and Clinical Foundations

    • Wolff established the fundamentals of bone remodeling and related shape/functionality changes.

Bone Mechanics at Whole Organism Level

  • Load Response

    • Cortical bone responds differently to bending vs. torsional loads.

    • Remodeling follows a dose-response relation to loading.

      • Factors: frequency, magnitude, duration of load

      • Torsion leads to more uniform remodeling at the periphery compared to bending.

Bone Homeostasis

  • Physiology of Bone Maintenance

    • Minimum of 4 mechanical pulses required daily for homeostasis.

    • More than 30 pulses daily results in new bone formation.

    • New bone forms in areas of greatest stress gradient, not just highest magnitude.

    • Source of studies: Clint Rubin and Ted Gross, SUNY Stony Brook

Microcracks and Damage in Bone

  • Effect of Aging and Gender on Microcracking

    • Young individuals show 0 cracks/mm² compared to about 5 cracks/mm² in the elderly.

    • Age-related increases in microcracks, particularly more pronounced in females.

    • Accumulation of cracks due to increased loading affects bone strength and remodeling.

      • Debate on whether these cracks lead to fractures is ongoing.

    • Cracks can form from cyclic loading at physiological levels or single traumatic events.

  • Consequences of Increased Microcracks

    • Microcracks reduce the available cross-sectional area for load resistance.

    • Debris may infiltrate canaliculi, compromising blood supply to osteocytes.

    • Triggers remodeling activity by osteoclasts and osteoblasts in response to damage.

Bone Fracture Statistics

  • Incidence of Fractures in the US

    • 250,000-300,000 hip fractures annually among people over 45 (projected to double/triple by 2050).

    • 500,000 vertebral (spinal) fractures yearly.

    • Expected outcomes by age 90: 1/3 of women and 1/6 of men may sustain hip fractures.

    • Increased mortality risk (12-20%) in patients with hip fractures compared to those without.

      • Study sources: Riggs and Melton (1988); Praemer et al (1999)

  • Annual Costs of Bone Fractures

    • Overall costs of fractures: $21.2 Billion, with hip fractures alone costing $8-10 Billion (approx. 36% of all fracture costs).

    • Anticipated increases in costs with an aging population.

Various Fractures and Their Mechanisms

  • Spinal Fractures

    • Result from shear loading on vertebrae due to external and muscular forces.

  • Femoral Fractures

    • Can involve complex, displaced distal femoral fractures that need stabilization from mechanical forces.

  • Bone Fracture Modes

    • Different types include:

      • Bending (with/without compression)

      • Torsion (spiral + axial)

      • Compression and tension fractures affecting mineral and collagen integrity.

Biological Factors Influencing Fracture Risk

  • Osteoporosis

    • Age-related bone loss marked as the most significant risk factor for fractures.

    • Associated risks include a notable decrease in both bone density and strength.

    • Risk factors can include falling due to muscle weakness or imbalanced proprioception.

      • Cited Source: Mow and Hayes [1997]

Changes in Bone with Aging and Injury

  • Challenges in Estimating Bone Strength

    • Complications arise in predicting strength/stiffness of bone through methods like Xray or CT scans.

Predicting Bone Fractures

  • Parameters Required for Prediction

    • Knowledge of tissue material properties and bone geometry.

    • Understanding loads experienced in vivo and analyzing internal stresses against known tissue strengths (both cortical and cancellous).

Fracture Stability and Healing Phases

  • Energy Consideration in Fractures

    • Bending fractures release more energy (90 N-m and 8 degrees at fracture) compared to torsion (30 N-m and 20-25 degrees).

    • Higher energy correlates to greater damage and complexity in stabilization processes.

  • Phases of Fracture Healing

    • Inflammation Phase

      • Cellular and vascular infiltration.

    • Repair Phase

      • Formation of a bony bridge.

    • Remodeling Phase

      • Restructuring back to original form/strength under Wolff’s Law principles or callus formation.

      • Typical duration before cast removal is 6-8 weeks.

Types of Fracture Healing

  • Primary Healing

    • Involves direct Haversian remodeling and osteon creation.

  • Secondary Healing

    • Characterized by spontaneous healing through intermediate steps involving periosteal and endosteal callus formation leading to scar tissue instead of bone if excessive mobility is present post-injury.

Inflammation in Fracture Healing

  • Bone heals at both outer (periosteal) and inner (endosteal) surfaces, with callus stabilization being essential for extracellular remodeling.

Repair Mechanisms

  • Bony bridge creation requires immobilization.

    • Non-union can occur with excessive mobility or large gaps filled with non-bone fibrous tissue.

  • Treatment Options

    • Regions needing stabilization can utilize flexible rods or plates to support fracture healing.

Plates vs. Rods for Fracture Stabilization

  • Plates

    • Provide rigid fixation but can lead to stress shielding.

    • Concern over vascular infiltration and callus size since plates can compress bone and increase long-term rigidity.

  • Rods

    • Axial loading is manageable but can cause excessive rotation problems while raising infection/sepsis risk, requiring careful use.

Fracture Healing and Delayed Repair

  • Significance of Delayed Healing

    • 5% to 10% of fractures face risks of delayed healing or non-union.

    • Murine models observed for studying molecular repair mechanisms and improving outcomes in human scenarios.

Objectives of Study on Bone Healing

  • Charcterization of differences in healing between stabilized critical (1.4mm wide) and sub-critical (0.6mm wide) transverse femoral defects in DT mice.

    • Focus on gene expression patterns (Col1/Col2) and biomechanical properties.

Surgical Techniques and Histological Methods

  • Technique

    • Attach anchor plate to bone with self-tapping screws.

  • Analysis

    • X-ray analysis with specific protocols (8 seconds exposure at 24 kV).

    • Histological & biomechanical examinations conducted to assess healing effectiveness.

Results of Bone Defect Study

  • Comparisons between sub-critical (0.6 mm defect) and critical (1.6 mm defect) healing processes, including expected expression of genes and physiological measuring techniques.

Scaffold Design and Bone Reconstruction

  • Goals of Tissue Engineering

    • Develop constructs to restore the structure and functional properties of damaged bones.

    • Options include self (autograft), cadaver (allograft), or synthetic scaffolds.

  • Clinical Treatment Statistics

    • Annual demand for treatment of bone defects (approx. 500,000 in the US).

    • Breakdown: 58% autografts, 34% allografts, 8% synthetic materials.

    • Global market for bone graft substitutes estimated around $1 billion with expected increases.

Construct Design Parameters

  • Requirements

    • Scaffolds must provide an initial mechanical stability and support for physiological stimuli favorable for healing.

    • Facilitate cellular growth and vascularization effectively.

Mechanical Properties of Bone Constructs

  • Design Challenges

    • Mechanical properties vary greatly, creating a need for different scaffolding solutions that resist collapse under various loading conditions.

    • Ensuring that scaffolds reflect the ideal balance of rigidity and biocompatibility.

Scaffold Performance and Evaluation

  • MicroCT for Evaluation

    • Investigating scaffold mineralization and reconstruction efficiencies through analysis of structural and cellular interactions.

Cell Therapy and Treatment Efficacy

  • Cell Implantation Options

    • Multiply options for stem or osteoprogenitor implantation to promote bone formation in various models with varying degrees of effectiveness.

  • Research Findings

    • Mixed results observed in bone formation rates with various scaffold applications and cell types across different studies.

Osteoinductive Factors in Bone Healing

  • Role of Bone Morphogenetic Proteins

    • Demonstrated effectiveness of demineralized bone matrix and growth factors in stimulating bone formation across species and contexts.

    • Gene therapy identified as a potential cost-effective option.

Concluding Insights on Bone Healing Technologies

  • Future Directions

    • Need to optimize and benchmark different bone regeneration strategies with a focus on efficacy, cost, and biomechanical interactions.

    • Importance of well-characterized model systems for effective outcome assessments and technology validations.