ch.1 lec 5+6

• Foreign Body Reaction (FBR)


  Complex interaction of cellular and molecular mechanisms initiated by the presence of a foreign material within the body
• Recognition and Adsorption


  1. Proteins from the surrounding tissue adsorb onto the surface of the biomaterial, forming a protein corona

  2. Protein corona influences the subsequent cellular response

  
• Inflammatory Response


  1. Macrophages recognize the foreign material as a threat

  2. Macrophages adhere to the surface and attempt to phagocytose it

  3. Macrophages start an inflammatory response

  4. Certain biomaterials are resistant to degradation, leading to persistent macrophage activation

  5. Macrophages release pro-inflammatory cytokines, chemokines and other signalling molecules

  6. Neutrophils are recruited to the site of implantation in response to chemotactic signals

  7. Neutrophils phagocytose debris and release inflammatory mediators

  
• Foreign Body Giant Cell Formation

  1. Macrophages fuse together to form multinucleated foreign body giant cells (FBGCs)

  2. FBGCs attempt to engulf and degrade the foreign material but often fail due to the material's inertness or size

  3. FBGCs circulate and migrate through tissues to ingest and destroy both microbes and cellular debris
• Formation of Fibrous Capsule around biomaterials

  1. Fibroblasts are recruited to the site of implantation

  2. Fibroblasts deposit extracellular matrix components such as collagen and fibronectin

  3. Deposited extracellular matrix leads to the formation of a fibrous capsule around the biomaterial

  4. Fibrous capsule acts as a physical barrier isolating the biomaterial from the surrounding tissue

  5. Fibrous capsule undergoes maturation over time, with changes in its composition and organization

  6. Granuloma can undergo necrosis if the avascular inner layer of phagocytic cell dies

  7. Thickness and stability of the capsule can vary depending on factors such as the type of biomaterial, its surface properties, and the host response

  
• Excessive fibrous encapsulation can damage the functionality of implanted devices and may lead to complications such as device failure or discomfort
• Chronic Inflammation


  1. Inflammatory response keeps at chronically

  2. Leads to sustained immune cell activation and tissue damage

  3. Can result in complications such as implant failure or discomfort
• Factors Influencing Foreign Body Reaction

  • Size and shape of the implanted biomaterial
  • Implantation site (location) within the body
  • Host factors (immune system, genetics, age, health status, vascularization, anatomy and physiology)
  • Sterilization and processing
  • Surface chemistry of biomaterials
  • Materials properties (composition, surface topography, mechanical properties, hydrophilicity/hydrophobicity, chemical stability, electrical properties, degradation rate)
• Larger materials


  May provoke a more definite immune response due to increased surface area for interaction with immune cells
• Materials with sharp edges or irregular shapes

  May induce more inflammation compared to smooth, rounded surfaces
• Certain tissues or organs

  May have a stronger immune response compared to others
• Factors at the implantation site

  Blood flow, tissue vascularity, and mechanical forces can influence the FBR
• Immune System


  The host's immune system is a primary determinant of the FBR
• Genetics


  Genetic factors can influence the host response to implanted biomaterials
• Age


  Age-related changes in the immune system and tissue physiology can impact the FBR
• Health Status


  Underlying medical conditions, medications, and lifestyle factors can influence the FBR
• Vascularization


  The presence of suitable blood supply and tissue vascularity at the implantation site is crucial for tissue healing and integration with implanted biomaterials
• Anatomy and Physiology


  The specific anatomical location of implantation within the body can influence the FBR
• Sterilization techniques


  May alter the surface properties of the biomaterial and influence its interaction with the host tissue
• Protein Adsorption


  The surface chemistry of biomaterials determines their interaction with proteins in the surrounding tissue

  
• Cell Adhesion


  Surface chemistry influences cell adhesion and spreading on biomaterial surfaces
• Inflammatory Response


  The chemical composition of the biomaterial surface can modulate the inflammatory response
• Bioactivity / Incorporation of Bioactive Molecules

  Biomaterials can be functionalized with bioactive molecules to modulate the FBR
• Surface Modification


  Surface modifications can alter the interactions between the biomaterial and host tissue
• Composition


  The chemical composition of the biomaterial plays a crucial role in determining its biocompatibility and the intensity of the FBR
• Surface Topography


  The surface topography of the biomaterial can influence the FBR
• Materials Properties


  • Composition
  • Surface topography (roughness, porosity, and surface patterning)
  • Mechanical properties (stiffness, elasticity, toughness, fatigue resistance, viscoelasticity and strength)
  • Hydrophilicity / hydrophobicity
  • Chemical stability
  • Electrical properties
  • Degradation rate
• Materials that are biocompatible and closely mimic the properties of native tissue tend to elicit a milder foreign body reaction (FBR)
• Surface Topography


  The surface topography of the biomaterial, including features such as roughness, porosity, and surface patterning, can influence cell adhesion, protein adsorption, and immune cell activation

  
• Mechanical Properties


  The mechanical properties of the biomaterial, such as (stiffness, elasticity, toughness, fatigue resistance, viscoelasticity and strength) can impact the FBR
• Hydrophilicity /Hydrophobicity


  The hydrophilicity or hydrophobicity of the biomaterial surface can affect protein adsorption, cell adhesion, and immune cell activation
• Chemical Stability


  The chemical stability of the biomaterial affects its long-term performance and the duration of the FBR
• Electrical Properties


  Some biomaterials exhibit electrical conductivity or piezoelectric properties, which can influence cell behavior and tissue regeneration
• Degradation Rate


  Biomaterials that degrade over time release degradation by-products into the surrounding tissue, which can cause an inflammatory response
• Several regulatory affairs organizations are responsible for setting biocompatibility testing criteria and guidelines
• Current regulations, whether in accordance with the U.S. Food and Drug Administration (FDA), the International Organization for Standardization (ISO 10993-1), or the Japanese Ministry of Health and Welfare (JMHW), require that manufacturers conduct adequate safety testing of their finished devices through pre-clinical and clinical phases as part of the regulatory clearance process
• FDA


  The FDA is responsible for medical device regulation and provides guidance on biocompatibility testing and assessment
• FDA device classes


  • Class I
  • Class II
  • Class III
• Class I Devices


  Medical devices in the Class I category have the least amount of regulatory control and minimize potential harm to the patient
• Class II Devices


  Class II medical devices require more FDA regulation to assure safety and effectiveness